ODYSSEY: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Treating Inflammatory Lung Injury and Improving Clinical Outcomes Associated With Severe or Critical COVID-19 Infection
Latest Information Update: 09 Feb 2023
At a glance
- Drugs Tradipitant (Primary) ; Tradipitant (Primary)
- Indications COVID 2019 infections; COVID-19 pneumonia
- Focus Registrational; Therapeutic Use
- Acronyms COVIDL1; ODYSSEY
- Sponsors Vanda Pharmaceuticals
- 01 Sep 2021 Results reporting carriers of stop-gain IFNAR2 (NM_000874:exon9:c.C966A:p.Y322X) in cohort of severe COVID-19 patients published in the Journal of Global Antimicrobial Resistance
- 03 Aug 2021 Primary endpoint has not been met. (Time to improvement on a 7-point ordinal scale as compared to baseline), according to a Vanda Pharmaceuticals media release.
- 03 Aug 2021 According to a Vanda Pharmaceuticals media release, company will continue the genetics component of the study with the goal of identifying genetic susceptibility factors contributing to the incidence of severe pneumonia among patients infected with the SARS-CoV-2 virus.
Most Recent Events
Trial Overview
Outcome
Purpose
This is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection. On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.
Comments
According to a Vanda Pharmaceuticals media release, an independent data and safety monitoring board (DSMB) recommended to terminate this study for futility, based on the planned interim analysis that determined that the study is unlikely to show a significant difference between treatment arms at the pre-specified primary endpoint. The DSMB also determined that there were no safety concerns that contributed to its recommendation.
Primary Endpoints
Time to improvement on a 7-point ordinal scale as compared to baseline
time_frame: 14 days or discharge [1]
The primary endpoint is the percentage of responders at day 28, as defined by an improvement of 2 or more points on a clinical status 7-point scale as compared to baseline. The primary endpoint will be summarized in Kaplan-Meier survival curve, and the treatment difference will be tested by the log-rank test in the ITT population.
The statistical analyses will be detailed in the statistical analysis plan (SAP).
Timepoint: Day 28
Other Endpoints
Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6)
time_frame: 14 days or discharge
Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples
time_frame: 14 days or discharge
In-hospital mortality
time_frame: 14 days or discharge
Mean change in NEWS2 score from baseline
time_frame: 14 days or discharge
Understand the effect of genetics for treatment response through whole genome sequence of the participant and the COVID-19 virus
time_frame: 14 days or discharge
Reduction from baseline of NRS for cough
time_frame: 14 days or discharge
Reduction from baseline of NRS for nausea
time_frame: 14 days or discharge
Time to normalization of fever for at least 48 hours
time_frame: 14 days or discharge
Time to improvement in oxygenation for at least 48 hours
time_frame: 14 days or discharge [2]
Diseases Treated
Indication | Qualifiers | Patient Segments |
---|---|---|
COVID 2019 infections | treatment | - |
COVID-19 pneumonia | treatment | severe |
Biomarker
NCT Number | Biomarker Name | Biomarker Function |
---|---|---|
NCT04326426 | Interleukin-6 (IL-6) | Outcome Measure |
Subjects
- Subject Type patients
-
Number
Planned: 300
Actual: 153
- Sex male & female
- Age Group 18-90 years; adult; elderly
Patient Inclusion Criteria
- Adults aged 18-90 - Confirmed laboratory COVID-19 infection by RT-PCR - Meeting severe or critical criteria of COVID-19 infection as defined at treating hospital - Confirmed pneumonia by chest radiograph or computed tomography - Fever defined as temperature ≥ 36.6 °C armpit, ≥ 37.2 °C oral, or ≥ 37.8 °C rectal - Oxygen saturation less than 92%
Patient Exclusion Criteria
- Recent use of illicit drugs or alcohol abuse - Known allergy to tradipitant or other neurokinin-1 antagonists - Pregnancy - Known HIV, HBV, or HCV infection - Malignant tumor, other serious systemic diseases - Inability to provide informed consent or to have an authorized relative or designated person provide informed consent, or to comply with the protocol requirements
Trial Details
Identifiers
Identifier | Owner |
---|---|
NCT04326426 | ClinicalTrials.gov: US National Institutes of Health |
EudraCT2020-005526-29 | European Clinical Trials Database |
VLY686-3501 | - |
VP-VLY686-3501 | - |
Organisations
- Sponsors Vanda Pharmaceuticals
- Affiliations Vanda Pharmaceuticals
Trial Dates
-
Initiation Dates
Planned : 01 Apr 2020
Actual : 13 Apr 2020
-
Primary Completion Dates
Planned : 01 Aug 2020
-
End Dates
Planned : 31 Aug 2020
Other Details
- Design double-blind; multicentre; parallel; prospective; randomised
- Phase of Trial Phase III
- Location France; USA
- Focus Registrational; Therapeutic Use
Interventions
Drugs | Route | Formulation |
---|---|---|
TradipitantPrimary Drug | Nasogastric |
-
|
TradipitantPrimary Drug | Oral | Capsule |
Tradipitant
Tradipitant 85 mg PO BID
Drug: Tradipitant (Neurokinin-1 antagonist)
Placebo
2 capsules of matching placebo
Drug: Placebo (Matching placebo)
Results
Therapeutic efficacy
In interim data from the phase III ODYSSEY trial, 14 day treatment with tradipitant demonstrated statistically significant treatment accelerated clinical improvement by day 7 (HR = 2.55, p = 0.0375) in 60 patients with inflammatory lung injury associated with severe or critical COVID-2019 infections. The benefit was generally consistent among patients of varying degree of severity at baseline. Tradipitant showed numerically improved median time to clinical improvement by day 28 (HR = 1.55, p = 0.2254) when compared with placebo, with median time to improvement 10 days for tradipitant and 28 days for placebo. Overall rates of improvement were similar for both treatment arm and placebo arm and was observed in 57% of patients treated with tradipitant and 50% for placebo.The mortality rate was also similar between the treatment groups with 14.2% for tradipitant and 16.6% for placebo [3]
Publications
-
Vanda Pharmaceuticals. Vanda Pharmaceuticals' Interim Analysis from ODYSSEY Study Shows Tradipitant may Accelerate Clinical Improvement in Patients with COVID-19 Pneumonia. Media-Rel 2020;.
Media Release -
Loss-of-function mutations in IFNAR2 in COVID-19 severe infection susceptibility. Internet-Doc 2021;.
Available from: URL: https://www.sciencedirect.com/science/article/pii/S2213716521001569?via%3Dihub -
Smieszek S. Late Breaking Abstract - Increased Substance P levels in COVID-19 hospitalized patients. ERS-2021 2021; abstr. N/A.
Available from: URL: https://erj.ersjournals.com/content/58/suppl_65/OA4114
Trial Centres
Centres
Centre Name | Location | Trial Centre Country |
---|---|---|
Lenox Hill Hospital Northwell Health | New York, New York | USA |
Vanda Pharmaceuticals |
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|
-
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Trial History
Event Date | Event Type | Comment |
---|---|---|
09 Feb 2023 | Other trial event | Last checked against European Clinical Trials Database record. Updated 09 Feb 2023 |
10 Apr 2022 | Other trial event | According to ClinicalTrials.gov, the recruitment status of this study is unknown because the information has not been verified recently (last verified April 2020). Updated 10 Apr 2022 |
10 Apr 2022 | Other trial event | Last checked against the ClinicalTrials.gov record. Updated 10 Apr 2022 |
06 Oct 2021 | Other trial event | New source identified and integrated: (European Clinical trials database: EudraCT2020-005526-29). Updated 06 Oct 2021 |
08 Sep 2021 | Results | Results exploring the genetic variants associated with attenuated Substance P responses from patients enrolled in ongoing ODYSSEY COVID-19 clinical study (NCT04326426) presented at the 31st Annual Congress of the European Respiratory Society Updated 09 Feb 2022 |
01 Sep 2021 | Results | Results reporting carriers of stop-gain IFNAR2 (NM_000874:exon9:c.C966A:p.Y322X) in cohort of severe COVID-19 patients published in the Journal of Global Antimicrobial Resistance Updated 09 Aug 2021 |
03 Aug 2021 | Endpoint not met | Primary endpoint has not been met. (Time to improvement on a 7-point ordinal scale as compared to baseline), according to a Vanda Pharmaceuticals media release. Updated 06 Aug 2021 |
03 Aug 2021 | Other trial event | According to a Vanda Pharmaceuticals media release, company will continue the genetics component of the study with the goal of identifying genetic susceptibility factors contributing to the incidence of severe pneumonia among patients infected with the SARS-CoV-2 virus. Updated 05 Aug 2021 |
03 Aug 2021 | Other trial event | According to a Vanda Pharmaceuticals media release, an independent data and safety monitoring board (DSMB) recommended to terminate this study for futility, based on the planned interim analysis that determined that the study is unlikely to show a significant difference between treatment arms at the pre-specified primary endpoint. The DSMB also determined that there were no safety concerns that contributed to its recommendation. Updated 05 Aug 2021 |
03 Aug 2021 | Status change - discontinued | Status changed from recruiting to discontinued, according to a Vanda Pharmaceuticals media release. Updated 05 Aug 2021 |
18 Aug 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, as of July 15, 2020, 60 patients had enrolled and completed the study.The results from this interim analysis will be submitted for publication in a peer reviewed journal. Updated 22 Aug 2020 |
18 Aug 2020 | Interim results | Interim Results (n=60) published in the Vanda Pharmaceuticals Media Release Updated 22 Aug 2020 |
05 Aug 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, interim analysis will be conducted to determine next steps. Updated 10 Aug 2020 |
06 May 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, results from this study are expected in the third quarter of 2020. Updated 11 May 2020 |
20 Apr 2020 | Biomarker Update | Biomarkers information updated Updated 17 Sep 2021 |
15 Apr 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, first patient is enrolled in Vanda's clinical trial, ODYSSEY VLY-686-3501 (NCT04326426), yesterday at Lenox Hill Hospital in New York City. Updated 22 Apr 2020 |
15 Apr 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, Dr. Mina, Section Chief of Pulmonary Medicine, Director of Pulmonary & Critical Care Fellowship at Lenox Hill Hospital, is a lead ODYSSEY study investigator Updated 22 Apr 2020 |
15 Apr 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, With the strong leadership and health expertise of Northwell Health, we expect to be able to accelerate enrollment in this study and provide results in the coming months Updated 22 Apr 2020 |
14 Apr 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting, according to a Vanda Pharmaceuticals media release. Updated 22 Apr 2020 |
02 Apr 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, the company has received FDA permission to proceed with the study and announced the initiation of this study. Updated 13 Apr 2020 |
02 Apr 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, the study will begin at New York area hospitals and will enroll hospitalized patients with COVID-19 ARDS. Updated 13 Apr 2020 |
02 Apr 2020 | Other trial event | According to a Vanda Pharmaceuticals media release, the company start enrolling patients this month. Updated 13 Apr 2020 |
01 Apr 2020 | New trial record | New trial record Updated 01 Apr 2020 |
Table of Contents
References
-
Vanda Pharmaceuticals. Vanda Pharmaceuticals Closes Enrollment In The ODYSSEY Study Comparing Tradipitant And Placebo In Hospitalized COVID-19 Pneumonia Patients. Media-Rel 2021;.
Media Release -
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
Vanda Pharmaceuticals. Vanda Pharmaceuticals' Interim Analysis from ODYSSEY Study Shows Tradipitant may Accelerate Clinical Improvement in Patients with COVID-19 Pneumonia. Media-Rel 2020;.
Media Release -
Loss-of-function mutations in IFNAR2 in COVID-19 severe infection susceptibility. Internet-Doc 2021;.
Available from: URL: https://www.sciencedirect.com/science/article/pii/S2213716521001569?via%3Dihub -
Vanda Pharmaceuticals. Vanda Pharmaceuticals Reports First Quarter 2020 Financial Results. Media-Rel 2020;.
Media Release -
Vanda Pharmaceuticals. Vanda Pharmaceuticals Announces the Initiation of ODYSSEY, an FDA Approved Clinical Study of Tradipitant in Hospitalized Patients with Severe COVID-19 Pneumonia. Media-Rel 2020;.
Media Release -
European Clinical Trials Database. Trial-Reg 2023;.
Available from: URL: https://www.clinicaltrialsregister.eu -
Vanda Pharmaceuticals. Vanda Pharmaceuticals Reports Second Quarter 2020 Financial Results. Media-Rel 2020;.
Media Release -
Smieszek S. Late Breaking Abstract - Increased Substance P levels in COVID-19 hospitalized patients. ERS-2021 2021; abstr. N/A.
Available from: URL: https://erj.ersjournals.com/content/58/suppl_65/OA4114 -
Vanda Pharmaceuticals. Vanda Pharmaceuticals, Northwell Health Conduct ODYSSEY Trial In Patients With Severe COVID-19 Pneumonia. Media-Rel 2020;.
Media Release
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