INO 4800
Alternative Names: COVID-19 DNA Vaccine - Inovio Pharmaceuticals; INO-4800Latest Information Update: 03 Nov 2022
At a glance
- Originator Inovio Pharmaceuticals; University of Pennsylvania
- Developer Advaccine (Suzhou) Biopharmaceuticals; Beijing Advaccine Biotechnology; Inovio Pharmaceuticals; World Health Organization
- Class COVID-19 vaccines; DNA vaccines; Viral vaccines
- Mechanism of Action CD4-positive T lymphocyte stimulants; CD8 positive T lymphocyte stimulants; Immunostimulants
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity No
Highest Development Phases
- Phase III COVID 2019 infections
Most Recent Events
- 27 Oct 2022 Discontinued - Phase-II for COVID-2019 infections (Prevention) in South Korea (Intradermal)
- 27 Oct 2022 Discontinued - Phase-III for COVID-2019 infections (Prevention) in Thailand, India, Mexico, Colombia, Brazil, USA (Intradermal)
- 11 Oct 2022 700320589 - CTP Push (NCT04642638): updated trial termination info in the KDM & added relevant HE
Development Overview
Introduction
INO 4800 is a DNA vaccine being developed by World Health Organization (WHO) in collaboration with Inovio Pharmaceuticals, using DNA medicine platform, for the prevention of COVID-2019 infections. The DNA medicine platform delivers optimised DNA into cells, where it is translated into proteins that activate an individual's immune system to generate a targeted T cell and antibody response. INO 4800 effectively generates a humoral immune response (including neutralizing antibodies) and/or cellular responses (both CD4- and CD8-positive T cells) in the vaccinated individuals. Clinical development is underway in China, Colombia, Mali and the Philippines.
Clinical development was underway in Brazil, Colombia, India, Mali, Mexico, Philippines, South Korea, Thailand and the US however, in October 2022, Inovio AS announced that it has discontinued the development of INO 4800. The decision was based on INOVIO's comprehensive review of its portfolio, market conditions, and global demand for COVID-19 vaccines. It continues to be investigated by the World Health Organization as part of their Solidarity Trial Vaccines. INOVIO's partner in China, Advaccine, will continue to develop INO 4800 as a COVID-2019 heterologous booster vaccine with its own resources. Advaccine is currently analyzing the data from its heterologous boost trial with INO 4800. Any future updates on this trial will be provided by Advaccine [1] .
The Inovio Pharmaceuticals' technology platform uses two key elements which comprises of SynCon® DNA sequence design process and CELLECTRA® DNA delivery technology. The SynCon DNA immunotherapy is injected into the muscle or skin and CELLECTRA® DNA delivery technology which uses a brief electrical pulse to open small pores in the cell reversibly to allow the plasmids to enter. Once inside the cell, the plasmids begin replicating, thereby strengthening the body's own natural response mechanisms.
Company Agreements
In October 2021, INOVIO signed non-binding memorandum of understanding (MOU) with Colombia's Ministry of Health and Social Protection for INO 4800 reflecting the intent to advance efforts to combat the pandemic and endemic threat posed by COVID-19 and to better prepare for future public health emergencies. The MOU creates a framework for a collaboration arrangement under which INOVIO and the government plan to explore knowledge sharing, technology licensing, and capacity building that support developing and producing vaccines and other biopharmaceuticals in Colombia. [2]
In January 2021, Inovio Pharmaceuticals and Advaccine-(Suzhou)-Biopharmaceuticals entered into a collaboration and license agreement for the development of COVID-2019 vaccine candidate, INO 4800. Under the terms of the agreement, Advaccine will have the exclusive right to develop, manufacture and commercialize INO 4800 within greater China, inclusive of Mainland China, Hong Kong, Macao, and Taiwan. Advaccine will license its plasmid manufacturing process for use with INO 4800 and other INOVIO pipeline product candidates to Inovio with the right to sublicense to Inovio's manufacturing partners. Additionally, Advaccine will provide its clinical data to Inovio in support of Inovio's global INO 4800 regulatory filings and Inovio will provide its INO 4800 clinical data for Advaccine to incorporate into its marketing applications in Greater China. Advaccine will make to Inovio an upfront payment of US$3.0 million as well as pay an aggregate of US$108.0 million upon the achievement of specified development and sales-based milestones for INO 4800 in Greater China. Inovio will be entitled to receive a royalty equal to a high single-digit percentage of annual net sales in each region within Greater China. In June 2021, Inovio announced expansion of this agreement with Advaccine to jointly conduct a global phase III segment of the INNOVATE phase II/III trial of INO 4800 primarily in Latin America, Africa and Asia. Under this expanded collaboration, the companies will equally share the total cost of the planned phase III trial, which is estimated to be approximately US$100 million, subject to specified limitations and conditions. Advaccine will obtain rights to additional Asian countries outside of greater China. [3] [4] [5]
In March 2020, Inovio Pharmaceuticals entered into a manufacturing agreement with Ology Bioservices (now National Resilience) to manufacture Inovio’s DNA vaccine INO 4800 for prevention of infection with the COVID-19 virus. The Department of Defense (DOD) awarded Ology Bioservices with a contract valued at $US11.9 million to work with Inovio on DNA technology transfer to rapidly manufacture the DNA vaccine. [6] [7]
In January 2020, Inovio Pharmaceuticals entered into a collaboration with Beijing Advaccine Biotechnology to advance the development of INO 4800 in China against COVID-2019 infections. Under the collaboration, the expertise of Advaccine will be utilised to conduct a phase I trial in China for COVID-2019 infections. Inovio Pharmaceuticals and Beijing Advaccine Biotechnology will also seek additional grant funding and further collaborations with vaccine companies in China to increase the speed of future testing of INO 4800. Financial details were not disclosed. [8] [3]
In June 2020, Inovio Pharmaceuticals partnered with International Vaccine Institute and Seoul National University for initiation of phase I/II clinical trial of INO 4800. Earlier IVI and SNU Hospitals also collaborated for phase I/IIa trials for a MERS coronavirus vaccine INO 4700 [9]
Key Development Milestones
In October 2021, the World Health Organization (WHO) initiated the phase III trial to evaluate safety, and efficacy of INO 4800 and MVC COV1901 [see AdisInsight drug profile 800059722] for the prevention of COVID-2019 infections (Solidarity Trial Vaccines). INO 4800 was selected by the WHO's independent vaccine prioritization advisory group, for inclusion in this global trial. The WHO and the Ministries of Health and Governments of Colombia, Mali, and the Philippines are co-sponsoring Solidarity Trial Vaccines. This randomised controlled trial is enrolling patients in Colombia, Mali, and the Philippines [10] [11] [12] .
In August 2021, Inovio Pharmaceuticals received regulatory allowance for two clinical trials investigating INO 4800, through its partner Advaccine-(Suzhou)-Biopharmaceuticals and Sinovac Biotechnology. The trials will evaluate the safety, tolerability and immunogenicity of heterologous prime-boost sequential immunizations using INO 4800 and SARS CoV 2 vaccine inactivated [see Adis Insight Drug Profile 800058206] in China [5] .
In October 2022, Inovio Pharmaceuticals terminated the phase II/III INNOVATE trial due to prioritize Inovio's COVID-19 efforts to advance a heterologous booster strategy and optimize potential impact on global public health. The trial was designed to evaluate safety, immunogenicity and efficacy of INO 4800 in prevention of COVID-2019 infections (COVID19-311; U1111-1266-9952; NCT04642638). The randomised, double-blind, placebo-controlled trial was initiated in November 2020 and enrolled 1308 healthy volunteers in Brazil, Colombia, India, Philippines, Mexico, Thailand and the US.
In March 2022, Inovio Pharmaceuticals suspended the phase II/III INNOVATE trial. First subject in the trial is dosed in December 2020. In the same month, the US FDA cleared the IND application for phase II segment of phase II/III INNOVATE (INOVIO INO-4800 Vaccine Trial for Efficacy) trial of INO 4800 in the US, following the company's response to questions raised by the US FDA. The primary endpoint of the phase III segment will be virologically-confirmed COVID-2019 disease. The trial is funded by the US Department of Defense (DoD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD (HA)) and the Defense Health Agency (DHA). In August 2021, the company received regulatory authorisation from Brazil's ANVISA (Agência Nacional de Vigilância Sanitária) to initiate the global phase III portion of phase II/III INNOVATE trial in multiple countries, including Brazil. In October 2021, INOVIO received authorisation from Colombia's INVIMA (Instituto Nacional de Vigilancia de Medicamentos y Alimentos, or the National Food and Drug Surveillance Institute), to conduct the phase III segment of INOVIO's global phase II/III INNOVATE trial in Colombia for COVID-19. As of October 2021, the company had received regulatory authorisation to proceed trial in Brazil, Philippines, and Mexico. In May 2021, Inovio Pharmaceuticals released positive results from the phase II segment of the clinical trial. The company also announced the selection of 2.0 mg dose for the phase III segment of the trial. The company received regulatory approvals to initiate a global phase III portion in Colombia, Mexico, Brazil and Philippines. In November 2021, Inovio Pharmaceuticals received authorisation from India's Central Drugs Standard Control Organization (CDSCO)'s Drug Controller General of India (DCGI) to proceed with the phase III portion of trial in India. In November 2021, the US FDA provided authorisation to proceed with the phase III segment of this phase II/III INNOVATE trial in the US. The US FDA had lifted the partial clinical hold on the phase III segment of this trial following the US FDA's review of additional non-clinical, clinical, and device information provided by the company. In September 2020, phase III segment of the trial was placed on partial clinical hold based on the US FDA's additional questions related to the trial and the CELLECTRA® 2000 device to be used to deliver INO 4800 directly into the skin. Inovio Pharmaceuticals, in collaboration with Advaccine Biopharmaceuticals Suzhou, will conduct the phase III part in the US, Latin America, Asia, and Africa. As of November 2021, the company had received regulatory authorisation to conduct this phase III trial in seven countries, including Thailand [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [22] . As of December 2021, the company plans to seek regulatory approval to amend the primary endpoint of the phase III INNOVATE trial from prevention of virologically confirmed COVID-19 disease to prevention of severe disease due to COVID-19. The company had paused enrollment in this trial in preparation for this potential change [10] .
In December 2020, Inovio Pharmaceuticals and Advaccine Biopharmaceuticals initiated and dosed the first patient in a phase II trial to evaluate safety and immunogenicity of INO 4800 in prevention of COVID-2019 infections. The dosing regimen involves two vaccinations at 0 and 28 days with either 1mg or 2mg dosing levels and is similar to the phase II segment of phase II/III INNOVATE trial [see above]. This trial intends to enrol approximately 640 volunteers in China. In January 2022, the company completed the trial enrollment [24] [3] .
In May 2022, INOVIVO completed a phase II trial that evaluated safety, tolerability and immunogenicity of INO 4800 administered by intradermal injection followed by electroporation (EP) using the CELLECTRA® 2000 device in healthy adults (NCT04447781;IVI COVID19-001). The randomised trial was initiated in August 2020 and enrolled 79 patients in South Korea and China. As of May 2021, INOVIVO initiated the phase II part of the phase I/II clinical trial [25] [26] .
In August 2020, INOVIO and Beijing Advaccine initiated phase I trial for the prevention of COVID-19 infection in patients in China [27] . In April 2020, the Korean Ministry of Food and Drug Safety approved clinical trials of COVID-19 vaccines through fast approval process [9] . In October 2021, INOVIO announced an online preprint publication of the trial in MedRxiv. The study demonstrated that INO 4800 produced robust immune responses among the phase 1 cohort of 120 patients of which 82.5%, or 99 participants, received a booster (or third) dose and was well-tolerated as both a two-dose series and as a homologous booster dose in all adults, including participants 65 years of age and older. Of note, a durable antibody response was observed six months following the second dose, and a homologous booster dose administered 6 to 10.5 months following the second dose also significantly increased antibody and T cell responses. INO 4800 was well-tolerated, with no treatment-related serious adverse events reported. Most adverse events were mild in severity and did not increase in frequency with age and subsequent dosing [28] .
In February 2022, INOVIO completed the phase I trial. In July 2020, INOVIO announced expansion of phase I trial to add older participants (NCT04336410; COVID19-001). Earlier in April 2020, trial was initiated to evaluate the safety, tolerability and immunological profile of INO 4800 administered by intradermal (ID) injection followed by electroporation (EP) using CELLECTRA® 2000 device in healthy adult volunteers. The open-label trial, enrolled approximately 120 volunteers in the US. In August 2020, positive interim safety and efficacy data from the trial was released by INOVIVO. In December 2020, safety and efficacy data from the trial was released by INOVIVO. In April 2021, updated efficacy data from the trial was released by the company, demonstrating T cell response against UK, South African and Brazilian variant strains [29] [27] [30] [31] [32] [33] [34] .
In September 2021, pooled data from the phase II/III INNOVATE trial and a phase I trial [see trials above], for the prevention of COVID-2019 infections, were presented at the IDWeek (IDW-2021) [35] .
In April 2020, the US FDA has accepted the Investigational New Drug (IND) application for INO 4800 for the prevention of COVID-19 infection [33] .
As of March 2022, Inovio Pharmaceuticals released preclinical studies data of INO 4800 against the Omicron variant of SARS-CoV-2 [10] .
In September 2021, Inovio Pharmaceuticals presented clinical data of INO 4800 from vaccinated subjects against COVID-19 infection at the IDWeek 2021 (IDW-2021) [36] .
Results from an analysis conducted in clinical samples showed that INO 4800 maintained a robust T cell level against the delta variant, compared with T-cell responses from the original wildtype strain, further demonstrating the ability of the drug to generate CD8 T cells, which could mitigate against rising variants such as delta. The data complements results from the phase I and II trials for INO 4800 [5] .
Results from cross prime-boost preclinical animal tests, conducted using INO 4800 and SARS CoV 2 vaccine inactivated [see Adis Insight Drug Profile 800058206], showed that the prime-boost strategy could stimulate high-level of antigen specific binding antibodies, neutralizing antibodies by both live-virus neutralization assay and hACE2 receptor blocking assay, and antigen-specific T cell immune responses [5] .
In preclinical studies, IN0 4800 demonstrated robust neutralizing antibody and T cell immune responses against coronavirus SARS-CoV-2 in mice and guinea pigs [37] . In July 2020, results from preclinical studies were released by INOVIO [38] .
As of July 2020, INOVIO initiated non-human primates (NHP) study to evaluate efficacy of INO 4800 at 12 months after vaccination. INO 4800 has also been selected by U.S. Operation Warp Speed for its COVID-19 non-human primate challenge study [38] [30] .
As of April 2020, Inovio is evaluating INO 4800 in many challenge studies in multiple animal models. The company also reported that they intend to deliver INO 4800 for additional studies and emergency use [32] .
Administration of INO 4800, generated immune response in animal models. The preclinical studies were initiated in January 2020 and is ongoing [39] .
Financing information
In April 2021, the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA)) and the Defense Health Agency (DHA), discontinued the funding for the phase III segment of the INNOVATE trial, while continue to fund the completion of the ongoing phase II segment [40] .
In January 2021, Invovio announced the pricing of an underwritten public offering of 17,700,000 shares of its common stock at a public offering price of $US8.50 per share and the new proceeds will be utilised for the clinical development of INO 4800 [41] .
As of August 2020, the Coalition for Epidemic Preparedness Innovations (CEPI), which awarded INOVIO a total of $US17.2 million in funding to date to support the phase I clinical trial of INO 4800 in the U.S. and a phase I/II clinical trial in South Korea [27]
In June 2020, INOVIO received $US 71 million funding from the US Department of Defense (DoD) to support the large-scale manufacture of the company's proprietary CELLECTRA® 3PSP smart device and the procurement of CELLECTRA® 2000 devices, which are used for the intradermal delivery of INO 4800. Initial development began in 2019 with $US 8.1 million funding from the medical arm of the US Defense Threat Reduction Agency's Medical CBRN Defense Consortium [42] .
In April 2020, Coalition for Epidemic Preparedness Innovations (CEPI) granted $US6.9 million funding to Inovio to support a phase I/II trial of INO 4800 for COVID-2019 infections in South Korea [43] .
In March 2020, Inovio received $US5 million grant from the the Bill & Melinda Gates Foundation to accelerate the testing and scale up of CELLECTRA® 3PSP proprietary smart device for the intradermal delivery of INO 4800, for the prevention of COVID-2019 infections [44] .
In February 2020, Twist Bioscience completed an offering of approximately 2.24 million shares of its common stock at an average price of approximately $US22.32 per share, raising approximately $US48.2 million in net proceeds [45] .
In January 2020, Coalition for Epidemic Preparedness Innovations (CEPI) awarded a grant of $US9 million to Inovio, to support preclinical and clinical development of INO 4800 for COVID-2019 infections [46] .
Drug Properties & Chemical Synopsis
- Route of administration Intradermal
- Formulation Injection
- Class COVID-19 vaccines, DNA vaccines, Viral vaccines
- Target CD4-positive T lymphocyte; CD8 positive T lymphocyte
- Mechanism of Action CD4-positive T lymphocyte stimulants; CD8 positive T lymphocyte stimulants; Immunostimulants
-
WHO ATC code
J07B-X (Other viral vaccines)
-
EPhMRA code
J7E9 (All other viral vaccines)
Biomarkers Sourced From Trials
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| INO 4800 | Interferon Gamma (IFNg) | Outcome Measure |
| T-cell surface antigen CD4 | Eligibility Criteria |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| COVID 2019 infections | Solidarity Trial Vaccines | Prevention | Phase III | Colombia, Mali, Philippines | Intradermal / Injection | Inovio Pharmaceuticals, World Health Organization | 26 Oct 2021 |
| COVID 2019 infections | - | Prevention | Phase II | China | Intradermal / Injection | Beijing Advaccine Biotechnology, Inovio Pharmaceuticals | 10 Dec 2020 |
| COVID 2019 infections | Followed by Electroporation | Prevention | Discontinued (III) | Brazil, India, Mexico, Thailand, USA | Intradermal / Injection | Advaccine (Suzhou) Biopharmaceuticals, Inovio Pharmaceuticals | 27 Oct 2022 |
| COVID 2019 infections | - | Prevention | Discontinued (II) | South Korea | Intradermal / Injection | Inovio Pharmaceuticals | 27 Oct 2022 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Inovio Pharmaceuticals | Originator | USA |
| University of Pennsylvania | Originator | USA |
| University of Pennsylvania | Owner | USA |
| Inovio Pharmaceuticals | Owner | USA |
| Advaccine (Suzhou) Biopharmaceuticals | Licensee | China, Hong Kong, Macau, Taiwan |
| Bill & Melinda Gates Foundation | Funder | USA |
| Department of defence | Funder | USA |
| Coalition for Epidemic Preparedness Innovations | Funder | Norway |
| Twist Bioscience | Collaborator | USA |
| World Health Organization | Collaborator | Switzerland |
| Fudan University | Collaborator | China |
| Beijing Advaccine Biotechnology | Collaborator | China |
| Seoul National University Hospital | Collaborator | South-Korea |
| University of Texas | Collaborator | |
| Universite Laval | Collaborator | Canada |
| International Vaccine Institute | Collaborator | South-Korea |
| Wistar Institute | Collaborator | USA |
Scientific Summary
Adverse Events
Results from the phase II segment of a phase II/III INNOVATE trial showed that INO 4800 was safe and well-tolerated in the participants (n=400). The majority of adverse events (AEs) were grade 1 and grade 2 in severity and was not reported to increase in frequency with the second dose. The number of participants experiencing each of the most common AEs did not differ between the two dosing groups [17] [22] .
Interim results from phase I trial demonstrated that administration of INO-4800 was generally safe and well tolerated in healthy participants for 8 weeks. Six reported mild (all Grade 1 in severity), transient adverse events, such as minor injection site reactions, related to vaccine dose. No serious adverse events were reported [29] [27] [30] [34] .
Treatment with INO 4800 was safe and generally well tolerated, in participants (n=401), for the prevention of COVID-2019 infections, in the phase I and phase II/III INNOVATE trials. Participants in the phase I trial received 0.5mg, 1.0mg or 2.0mg intradermally (ID) followed by electroporation (EP) at days 0 and 28. An optional booster dose was administered >6 months post-dose 2. The phase II trial further compared the 1.0mg and 2.0mg doses against placebo, randomized at a 3:3:1:1 ratio. The majority of adverse events (AEs) related to INO 4800 across both trials were mild in severity and did not increase in frequency with age and subsequent doses [35] [22] .
Pharmacodynamics
Summary
In preclinical studies, administration of INO 4800 protected from live virus challenge at 13 week after last vaccination in rhesus macaques. The protection was mediated by T and B cells from INO-4800 vaccination. INO 4800 reduced viral load in both the lower lungs and nasal passages in macaques that received two doses of INO 4800 (1 mg) four weeks apart and then were challenged with live virus 13 weeks after the second dose (study week 17). The reduced viral loads following exposure to SARS-CoV-2 infection was observed in this at this timeframe demonstrating durable impact mediated by INO 4800. Immunisation with INO 4800 limits active viral replication as well as reduces viral shedding in the nasal cavity. administration of INO 4800 also reduces viral load against G614 mutants. INO 4800 vaccination generated antibodies neutralizing both the earlier strain of virus as well as the mutant variant (D614G) that has emerged with greater infectivity [38] . Earlier results from preclinical studies showed that administration of INO-4800 protected mice in SARS-CoV-2 viral challenge studies, where vaccination with INO 4800 prevented viral replication in the lungs of animals challenged with SARS-CoV-2 [30] .
In preclinical in vitro studies, INO 4800 maintained robust T cell responses, including CD8+ responses, against the Omicron variant of SARS-CoV-2. INO 4800 significantly decreased levels of both neutralizing and binding antibodies against Omicron, consistent with other vaccines [10] .
Immunogenicity
Summary
Results from the phase II segment of a phase II/II INNOVATE trial showed that the geometric mean fold rise (GMFR) of binding and neutralizing antibody levels in patients (n=400) resulting from INO 4800 were significantly greater in the 2.0 mg dose group versus the 1.0 mg dose group. The T cell immune responses measured by the ELISpot assay were also higher in the 2.0 mg dose group compared to the 1.0 mg dose group [17] [22] .
Updated results from phase I trial demonstrated T cell response and INO 4800 induced neutralising antibodies against UK, Brazilian and South African strains. The results showed that INO 4800 induced a robust T cell response against all spike protein variants tested. In addition, vaccine also demonstrated similar levels of neutralizing activity against the UK (B.1.1.7), South Africa (B.1.351) and Brazilian (P.1) variants as those against the original strain. Furthermore, INO-4800 generated robust neutralizing antibodies at levels against Brazilian variant which were comparable to those against the Wuhan strain. Earlier interim results from the trial demonstrated that 100% of participants achieved immunological response. 95% of vaccinated participants had overall seroconversion after two vaccine doses. Nearly 90% of vaccinated participants generated strong T cell responses. One participant in the 1.0 mg dose cohort and two participants in the 2.0 mg dose cohort were excluded in the immune analyses as they tested positive for COVID-19 immune responses at study entry, indicating prior infection [31] [29] [27] [30] [34] .
Treatment with INO 4800 showed good pharmacokinetics, in participants (n=401), for the prevention of COVID-2019 infections, in the phase I and phase II/III INNOVATE trials. Participants in the phase I trial received 0.5mg, 1.0mg or 2.0mg intradermally (ID) followed by electroporation (EP) at days 0 and 28. An optional booster dose was administered >6 months post-dose 2. The phase II trial further compared the 1.0mg and 2.0mg doses against placebo, randomized at a 3:3:1:1 ratio. In phase I trial, 78% (14/18) and 84% (16/19) of participants generated neutralising antibody responses with geometric mean titers (GMTs) of 17.4 (95%CI 8.3, 36.5) and 62.3 (95% CI 36.4, 106.7) in the 1.0 and 2.0 groups, respectively. By week 8, 74% (14/19) and 100% (19/19) participants generated T cell responses by Th1- associated IFNγ ELISPOT assay. Following a booster dose, neutralising GMTs rose to 82.2 (95% CI 38.2, 176.9) and 124.7 (95% CI 62.8, 247.7) in the 1.0mg and 2.0mg groups, respectively, demonstrating the ability of INO 4800 to boost. In the phase II study, neutralising antibody responses demonstrated GMTs of 93.6 (95%CI 77.3, 113.4) in the 1.0mg dose group and 150.6 (95%CI 123.8, 183.1) in the 2.0mg dose group. The candidate showed the induction of both humoral and cellular immune responses. In addition to eliciting neutralising antibodies, INO 4800 also induced T cell immune responses as demonstrated by IFNγ ELISpot. As a homologous booster, INO 4800, when administered 6-10.5 months following the primary series, resulted in an increased immune response without increase in reactogenicity. The 2.0mg dose was selected for phase III evaluation [35] [22] .
Clinical data from vaccinated subjects against COVID-19 infections showed that INO 4800 vaccination induced neutralising antibodies against all SARS-CoV-2 variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested. IgG binding titers were not impacted between wild-type (WT) and B.1.1.7 or B.1.351 variants. An average 1.9-fold reduction was observed for the P.1 variant in subjects tested at week 8 after receiving two doses of INO 4800. In a SARS-CoV-2 pseudovirus neutralization assay using sera collected from 13 subjects two weeks after administration of a third dose of INO 4800, observed neutralization against WT and the emerging variants in all samples tested. The mean ID50 titers for the WT, B.1.1.7, B.1.351 and P.1. were 643 (range: 70 - 729), 295 (range: 46 - 886), 105 (range: 25 - 309), and 664 (range: 25 - 2087), respectively. Compared to WT, there was a 2.1 and 6.9-fold reduction for B.1.1.7 and B.1.351, respectively, while there was no difference between WT and the P.1 variant. Comparion of cellular immune responses to WT and SARS-CoV-2 Spike variants elicited by INO 4800 vaccination, observed similar cellular responses to WT (median = 82.2, IQR = 58.9 - 205.3), B.1.1.7 (79.4, IQR = 38.9 - 179.7), B.1.351 (80, IQR = 40.0 - 208.6) and P.1 (78.3, IQR = 53.1 - 177.8) spike peptides [36] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 22 Sep 2021 | Trial Update | Inovio Pharmaceuticals plans a global phase III trial for COVID-2019 infections (Prevention) in September 2021 [18] | 18 Nov 2021 |
| 30 Sep 2020 | Trial Update | Inovio plans a phase II/III INNOVATE trial for COVID-2019 infections (Prevention) in USA (Intradermal) in September 2020 (700320589) [42] | 04 Dec 2020 |
| 30 Jun 2020 | Trial Update | Inovio in collaboration with International Vaccine Institute plans a phase I/IIa trial for COVID-2019 infections (Prevention) in South Korea (Intradermal) in June 2020 (NCT04447781) | 09 Aug 2020 |
| 30 Apr 2020 | Trial Update | Inovio plans a clinical trial for COVID-2019 infections (In volunteers) in USA (Parenteral) in April 2020 (700318014) [39] | 13 Apr 2020 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 27 Oct 2022 | Phase Change - Discontinued(II) | Discontinued - Phase-II for COVID-2019 infections (Prevention) in South Korea (Intradermal) [1] Updated 03 Nov 2022 |
| 27 Oct 2022 | Phase Change - Discontinued(III) | Discontinued - Phase-III for COVID-2019 infections (Prevention) in Thailand, India, Mexico, Colombia, Brazil, USA (Intradermal) [1] Updated 03 Nov 2022 |
| 11 Oct 2022 | Active Status Review | 700320589 - CTP Push (NCT04642638): updated trial termination info in the KDM & added relevant HE Updated 28 Oct 2022 |
| 11 Oct 2022 | Trial Update | Inovio Pharmaceuticals terminates the phase II/III INNOVATE trial in COVID-2019 infections (Prevention) in the US, Mexico and Colombia (Intradermal) due to prioritize Inovio's COVID-19 efforts to advance a heterologous booster strategy and optimize potential impact on global public health (NCT04642638) Updated 28 Oct 2022 |
| 25 May 2022 | Trial Update | International Vaccine Institute in collaboration with Inovio Pharmaceuticals completes its phase I/II trial in COVID-2019 infections (Prevention) in South Korea and China (Intradermal) (NCT04447781) Updated 28 Jul 2022 |
| 10 Feb 2022 | Trial Update | Inovio completes a phase I trial in COVID-2019 infections (Prevention) in USA (Parenteral) (NCT04336410) Updated 16 Mar 2022 |
| 31 Dec 2021 | Trial Update | Inovio Pharmaceuticals suspends and pauses enrolment in the phase III INNOVATE trial in COVID-2019 infections (Prevention) in USA, Thailand, Philippines, Mexico, India, Colombia, Brazil (Intradermal) (NCT04642638) [10] Updated 03 Mar 2022 |
| 09 Nov 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Prevention) in Thailand and USA (Intradermal) [13] (NCT04642638) Updated 03 Mar 2022 |
| 03 Nov 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Prevention) in India (Intradermal) [15] (NCT04642638) Updated 18 Nov 2021 |
| 03 Nov 2021 | Regulatory Status | The Drug Controller General of India approves clinical trial application for the phase III INNOVATE trial in COVID-19 infection (Prevention) [15] Updated 10 Nov 2021 |
| 27 Oct 2021 | Regulatory Status | Inovio received regulatory approval for clinical trial applications to initiate phase III INNOVATE trial in COVID-19 infection (Prevention) in Philippines, Mexico, Colombia and Brazil [16] Updated 29 Oct 2021 |
| 26 Oct 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Prevention) in Mali (Intradermal) [10] [11] [12] Updated 03 Mar 2022 |
| 26 Oct 2021 | Trial Update | World Health Organization initiates enrolment in a phase III trial for COVID-2019 infections (Prevention) in Philippines and Colombia (Intradermal) [10] [11] [12] Updated 03 Mar 2022 |
| 21 Oct 2021 | Trial Update | Inovio Pharmaceuticals plans a phase III segment of its global Phase II/III clinical trial for COVID-2019 infections in Colombia [2] Updated 25 Oct 2021 |
| 11 Oct 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Prevention) in Philippines, Mexico, Colombia, Brazil (Intradermal) [19] (NCT04642638) Updated 18 Nov 2021 |
| 11 Oct 2021 | Regulatory Status | Inovio receives approval for clinical trial application to initiate a phase III INNOVATE trial in COVID-19 infection (Prevention) in Philippines and Mexico [19] Updated 13 Oct 2021 |
| 11 Oct 2021 | Regulatory Status | The INVIMA approves clinical trial application to for the phase III INNOVATE trial in COVID-19 infection (Prevention) in Colombia [19] Updated 13 Oct 2021 |
| 29 Sep 2021 | Scientific Update | Immunogenicity data from clinical studies in COVID-2019 infections presented at the IDWeek 2021 (IDW-2021) [36] Updated 07 Feb 2022 |
| 29 Sep 2021 | Scientific Update | Pooled adverse events and immunogenicity data from the phase II/III INNOVATE trial and a phase I trial in COVID-2019 infections presented at the IDWeek (IDW-2021) [35] Updated 07 Feb 2022 |
| 09 Sep 2021 | Biomarker Update | Biomarkers information updated Updated 02 Oct 2021 |
| 26 Aug 2021 | Regulatory Status | The ANVISA (Agência Nacional de Vigilância Sanitária)approves clinical trial application to initiate a global phase III portion of its phase II/III INNOVATE trial in COVID-19 infection (Prevention) in Brazil [20] Updated 30 Aug 2021 |
| 09 Aug 2021 | Regulatory Status | Inovio Pharmaceuticals receives regulatory allowance for two clinical trials (heterologous prime-boost trials) for INO 4800 [5] Updated 12 Aug 2021 |
| 08 Jun 2021 | Licensing Status | Inovio Pharmaceuticals enters into an expanded agreement with Advaccine-(Suzhou)-Biopharmaceuticals to conduct planned global phase III trial for COVID-19 infections [4] Updated 14 Jun 2021 |
| 12 May 2021 | Trial Update | Inovio Pharmaceuticals plans a global phase III trial for COVID-2019 infections (Prevention) in September 2021 [18] Updated 18 Nov 2021 |
| 10 May 2021 | Phase Change - II | Phase-II clinical trials in COVID-2019 infections (Prevention) in South Korea (Intradermal) [25] Updated 18 May 2021 |
| 10 May 2021 | Regulatory Status | Inovio Pharmaceuticals plans to file preliminary phase II results and device data from the phase II/III INNOVATE trial with the US FDA [17] Updated 15 May 2021 |
| 10 May 2021 | Scientific Update | Safety and immunogenicity data from a phase II trial in COVID-2019 infections released by Inovio Pharmaceuticals [17] Updated 15 May 2021 |
| 23 Apr 2021 | Trial Update | Inovio Pharmaceuticals plans a phase III trial for COVID -2019 infections worldwide excluding USA [40] Updated 28 Apr 2021 |
| 16 Apr 2021 | Scientific Update | Immunogenicity data from a phase I trial in COVID-2019 infections released by Inovio [31] Updated 19 Apr 2021 |
| 06 Jan 2021 | Licensing Status | INO 4800 licensed to Advaccine-(Suzhou)-Biopharmaceuticals in Greater China, inclusive of Mainland China, Hong Kong, Macao, and Taiwan [3] Updated 06 Jan 2021 |
| 04 Jan 2021 | Trial Update | Inovio Pharmaceuticals completes enrolment in the phase II trial for COVID-2019 infections (Prevention) in China (Intradermal) [3] Updated 06 Jan 2021 |
| 24 Dec 2020 | Scientific Update | Updated immunogenicity and adverse events data from a phase I trial in COVID-19 infections released by INOVIO Pharmaceuticals [29] Updated 29 Dec 2020 |
| 10 Dec 2020 | Phase Change - II | Phase-II clinical trials in COVID-2019 infections (Prevention) in China (Intradermal) [24] Updated 15 Dec 2020 |
| 30 Nov 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections (Prevention) in USA (Intradermal, Injection) (NCT04642638) Updated 04 Dec 2020 |
| 16 Nov 2020 | Regulatory Status | The US FDA approves IND application for INO 4800 in COVID-2019 infections (Prevention) [23] Updated 23 Nov 2020 |
| 30 Sep 2020 | Regulatory Status | US FDA puts a partial hold on INOVIO's IND application for phase II/III trial in COVID-2019 infections (Prevention) [14] Updated 30 Sep 2020 |
| 28 Sep 2020 | Regulatory Status | INOVIO submits IND application to US FDA for a phase II/III trial in COVID-2019 infections (Prevention) before September 2020 [14] Updated 30 Sep 2020 |
| 10 Aug 2020 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections (Prevention) in China (Intradermal) [27] Updated 13 Aug 2020 |
| 10 Aug 2020 | Scientific Update | Interim adverse events and pharmacokinetics data from a phase I/II trial in COVID-19 infections released by INOVIO Pharmaceuticals [27] Updated 13 Aug 2020 |
| 04 Aug 2020 | Phase Change - I/II | Phase-I/II clinical trials in COVID-2019 infections (Prevention) in China (Intradermal) Updated 04 Dec 2020 |
| 04 Aug 2020 | Phase Change - I/II | Phase-I/II clinical trials in COVID-2019 infections (Prevention) in South Korea (Intradermal) [38] ( NCT04447781) Updated 09 Aug 2020 |
| 31 Jul 2020 | Scientific Update | Pharmacodynamics data from a preclinical trial in COVID-19 infections released by INOVIO [38] Updated 04 Aug 2020 |
| 31 Jul 2020 | Trial Update | INOVIO initiates a non-human primate (NHP) preclinical trial for COVID-19 infections prior to July 2020 [38] Updated 04 Aug 2020 |
| 30 Jul 2020 | Regulatory Status | The US government selects INO 4800 for Operation Warp Speed for COVID-2019 infections [38] Updated 16 Sep 2020 |
| 01 Jul 2020 | Scientific Update | Interim efficacy and adverse events and pharmacodynamic data from a preclinical and phase I trial in COVID-19 infections released by INOVIVO [30] Updated 03 Jul 2020 |
| 25 Jun 2020 | Trial Update | Inovio in collaboration with International Vaccine Institute plans a phase I/IIa trial for COVID-2019 infections (Prevention) in South Korea (Intradermal) in June 2020 (NCT04447781) Updated 09 Aug 2020 |
| 23 Jun 2020 | Trial Update | Inovio plans a phase II/III INNOVATE trial for COVID-2019 infections (Prevention) in USA (Intradermal) in September 2020 [42] Updated 04 Dec 2020 |
| 04 Jun 2020 | Licensing Status | INOVIO partners with International Vaccine Institute and Seoul National University Hospital for phase I/II clinical trial in COVID-2019 infections [9] Updated 09 Jun 2020 |
| 04 Jun 2020 | Regulatory Status | The Korean Ministry of Food and Drug Safety approves clinical trial for COVID-19 vaccine [9] Updated 09 Jun 2020 |
| 06 Apr 2020 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections (Prevention) in USA (Parenteral) (NCT04336410) [33] Updated 13 Apr 2020 |
| 06 Apr 2020 | Regulatory Status | US FDA accepts IND application for INO 4800 for COVID-19 [33] Updated 13 Apr 2020 |
| 06 Apr 2020 | Trial Update | INOVIO plans a phase II trial [33] Updated 13 Apr 2020 |
| 03 Mar 2020 | Trial Update | Inovio plans a clinical trial for COVID-2019 infections (In volunteers) in USA (Parenteral) in April 2020 [39] Updated 13 Apr 2020 |
| 03 Mar 2020 | Trial Update | Inovio plans a clinical trial for COVID-2019 infections in China and South Korea (Parenteral) [39] Updated 09 Mar 2020 |
| 30 Jan 2020 | Licensing Status | INO 4800 is available for licensing in China as of 30 Jan 2020. https://www.inovio.com/about#partnerships [8] Updated 04 Feb 2020 |
| 30 Jan 2020 | Licensing Status | Inovio Pharmaceuticals and Beijing Advaccine Biotechnology collaborates to develop INO 4800 in China for COVID-2019-infections [8] Updated 03 Feb 2020 |
| 30 Jan 2020 | Trial Update | Inovio Pharmaceuticals and Beijing Advaccine Biotechnology plans a phase I trial for COVID-2019-infections in China [8] Updated 03 Feb 2020 |
| 24 Jan 2020 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections (Prevention) in USA (Parenteral) [39] Updated 09 Mar 2020 |
| 23 Jan 2020 | Phase Change | Early research in COVID-2019-infections (Prevention) in USA (Parenteral) [46] Updated 28 Jan 2020 |
| 23 Jan 2020 | Trial Update | Inovio Pharmaceuticals plans a phase I trial for COVID-2019-infections [46] Updated 28 Jan 2020 |
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