CTV 05
Alternative Names: CTV-05; LACTIN-V; Lactobacillus crispatus CTV-05Latest Information Update: 31 Aug 2023
At a glance
- Originator GyneLogix
- Developer National Institute of Allergy and Infectious Diseases; Osel Inc; The Fertility Clinic, Skive; University of Washington
- Class Probiotics
- Mechanism of Action Bacteria replacements; Vaginal microbiome modulators
-
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 II/III Urinary tract infections
- Phase II Bacterial vaginosis
Most Recent Events
- 16 Aug 2023 The Fertility Clinic, Skive completes the phase II trial inBacterial vaginosis in Denmark (Vaginal) (NCT05166746) (EudraCT2016-002385-31)
- 10 May 2021 Phase-II clinical trials in Bacterial vaginosis in South Africa (Vaginal) (NCT05022212)
- 03 Feb 2021 Osel enters into a clinical trial licensing agreement with Danish Research Consortia (comprising Aarhus University, Skive Hospital and Statens Serum Institut of Denmark) for LACTIN-V for Bacterial vaginosis
Development Overview
Introduction
CTV 05 is a live biotherapeutic containing a strain of human Lactobacillus crispatus being developed by Osel. CTV 05 produces high levels of lactic acid and hydrogen peroxide and is delivered vaginally with a proprietary applicator. Many women lack sufficient populations of hydrogen peroxide-producing lactobacilli to maintain vaginal health, making them more susceptible to infection. CTV 05 may help to maintain a healthy, more acidic pH environment in the vaginal tract and protect women from exposure to potentially serious health risks. Studies have also shown that CTV 05 is able to colonise the vagina and consistently produce hydrogen peroxide. Clinical development is underway in South Africa, US and Denmark for the treatment of bacterial vaginosis, urinary tract infection and in patients with high risk of HIV.
Company Agreements
Osel, in February 2021, entered into licensing agreement with a consortia comprising, Aarhus University, Skive Hospital and Statens Serum Institut of Denmark, and obtained the exclusive worldwide license to inventions resulting from a phase II trial of LACTIN-V in women undergoing in-vitro fertilization. Financial terms of the agreement were not disclosed. [1]
GyneLogix Inc had been developing CTV 05 for gynaecological infections in the US in conjunction with the NIH's National Institute of Allergy and Infectious Disease (NIAID), Centers for Disease Control and Prevention (CDC), and the University of Pittsburgh. However, in August 1999, The Medicines Company acquired worldwide rights to CTV 05 from GyneLogix. At the time of acquisition, several phase I and II studies sponsored by the NIH had been completed. The Medicines Company has since announced that CTV 05 has been licensed to Osel Inc.
Key Development Milestones
In September 2015, University of Washington initiated a phase II/III trial to assess the efficacy of CTV 05 for the prevention of recurrent urinary tract infections (STUDY00000160; NCT03151967). The randomised trial in November 2017, completed enrollment of 27 patients in the US [2] .
In March 2023, Osel completes a phase II trial that assessed the impact of CTV 05 on the vaginal microbiome of lactobacillus-deficient young women in the South African FRESH study who are at high risk for HIV acquisition and bacterial vaginosis (NCT05022212, LV-007). The randomised, placebo-controlled trial was initiated in May 2021 and enrolled 45 healthy volunteers in South Africa [3] .
In August 2023, The Fertility Clinic, Skive completed the a phase II study evaluating the effect of CTV 05 and oral clindamycin and a live biotherapeutic on the reproductive outcomes of IVF patients with abnormal vaginal microbiota (NCT05166746; EudraCT2016-002385-31; AVM_Lacto_2015/582). The randomised, double-blinded and placebo-controled trial was initiated in December 2017 and enrolled 333 adult women in Denmark [4]
In August 2017, Osel and The Fertility Clinic, Skive initiated a phase II study evaluating the effect of CTV 05 and oral clindamycin on the reproductive outcome of IVF patients with abnormal vaginal microbiota (2015/582, EudraCT2016-002385-31). Clinical pregnancy rate in the patients treated was the primary outcome of the study. The study is designed to enrol 333 adult women of childbearing potential with abnormal vaginal microbiota undergoing first or second IVF treatment cycle [4] . First patient was dosed in the trial in January 2018 [5] .
According to Osel's pipeline, accessed in July 2015, the company is planning to conduct one or more pivotal studies of CTV 05 for FDA approval.
In February 2019, The National Institute of Allergy and Infectious Disease in collaboration with Osel, completed a phase IIb trial to estimate the efficacy of CTV 05 for the prevention of the recurrence of bacterial vaginosis (14-0029; HHSN272201300014I; NCT02766023). The randomised, double-blind, placebo-controlled trial initiated in May 2016, provided screening evaluation for the hypothesis that, following a 5-day treatment with metronidazole to treat bacterial vaginosis. CTV 05 reduced the 12-week incidence of bacterial vaginosis recurrence when compared with placebo. The trial enrolled 228 women in the US. In May 2020, Osel released data from the study demonstrating significant efficacy. Adverse events were similar in both treatment and placebo group [6] [7] [8] .
Osel completed a phase II trial of CTV 05 for the prevention of recurrent urinary tract infections in 100 women receiving one vaginal capsule containing lactobacilli in high concentration or placebo (NCT00305227). This trial was conducted in collaboration with the National Institutes of Diabetes and Digestive and Kidney Diseases and the University of Washington in the US. The primary outcome measure was the incidence of urinary tract infection after four months, while the secondary outcome measure was the incidence of vaginal discharge, also assessed after four months [9] .
In July 2009, Osel completed a phase II trial of CTV 05 in women with bacterial vaginosis. This randomised, double-blind, placebo-controlled, parallel assignment study evaluated the safety and efficacy of the drug when administered in combination with metronidazole in approximately 40 subjects in the US (NCT00635622). A phase I trial, initiated in November 2007, evaluated the safety of CTV 05 in 12 healthy pre-menopausal women in the US (NCT00537576).
In December 2004, Osel announced that it has completed its phase I trial of CTV 05 in patients with bacterial vaginosis. A second phase I trial of the drug in patients with recurrent urinary tract infections (UTIs) was also conducted [10] . Osel announced that it had filed a second IND for UTIs in July 2004 [11] . The initiation of two phase II trials of CTV 05 in the US, one for recurrent UTIs and another for recurrent bacterial vaginosis, was announced in April 2005 [12] [13] .
The Medicines Company, in conjunction with sponsorship and coordination from the NIAID, conducted a phase II clinical trial of CTV 05 in patients with bacterial vaginosis. In the trial, CTV 05 was administered as an adjunct to metronidazole, a standard antibiotic treatment. Study data indicated that while CTV 05 did not improve 30-day cure rates, vaginal colonisation rates of L. crispatus were significantly higher in CTV 05-treated patients, compared with placebo-treated patients. In its 2002 Form 10-K SEC filing, The Medicines Company stated that it had no plans for making significant new expenditures in connection with CTV 05, based on the trial results.
Drug Properties & Chemical Synopsis
- Route of administration Vaginal
- Formulation Capsule, Powder
- Class Probiotics
- Target Bacteria; Vaginal microbiome
- Mechanism of Action Bacteria replacements; Vaginal microbiome modulators
-
WHO ATC code
J05A (Direct acting antivirals)
V03A-X (Other therapeutic products)
-
EPhMRA code
J5C4 (HIV antivirals, entry inhibitors)
V3 (All Other Therapeutic Products)
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
bacterial vaginosis |
Brief Title |
Human Microbiome |
|
|
bacterial vaginosis |
Eligibility Criteria |
pyridoxal phosphatase |
|
|
bacterial vaginosis |
Official Title |
Human Microbiome |
|
|
HIV infections |
Outcome Measure |
Human Microbiome |
|
|
urinary tract infections |
Arm Group Label |
Alpha-Lactose |
|
|
urinary tract infections |
Eligibility Criteria |
Thiamine monophosphate PAMG-1 epithelial membrane protein 1 |
|
|
urinary tract infections |
Outcome Measure |
Alpha-Lactose |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| CTV 05 | Alpha-Lactose | Arm Group Label, Outcome Measure |
| epithelial membrane protein 1 | Eligibility Criteria | |
| Human Microbiome | Brief Title, Official Title, Outcome Measure | |
| PAMG-1 | Eligibility Criteria | |
| pyridoxal phosphatase | Eligibility Criteria | |
| Thiamine monophosphate | Eligibility Criteria | |
| TNFAIP3 interacting protein 2 | Brief Title |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Bacterial vaginosis | - | - | Phase II | Denmark | Vaginal / Capsule | Osel Inc, The Fertility Clinic, Skive | 24 Aug 2017 |
| Bacterial vaginosis | - | Recurrent | Phase II | USA | Vaginal / Capsule | Osel Inc | 04 Jul 2001 |
| Bacterial vaginosis | - | Prevention, Recurrent | Phase II | USA | Vaginal / Capsule | National Institute of Allergy and Infectious Diseases, Osel Inc | 11 May 2016 |
| Bacterial vaginosis | Volunteers at high risk of HIV acquisition | - | Phase II | South Africa | Vaginal / Powder | Osel Inc | 10 May 2021 |
| Urinary tract infections | - | Prevention, Recurrent | Phase II/III | USA | Vaginal / Capsule | University of Washington | 01 Sep 2015 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| GyneLogix | Originator | USA |
| GyneLogix | Owner | USA |
| Osel Inc | Licensee | World |
| Aarhus Universitetshospital | Collaborator | Denmark |
| University of Washington | Collaborator | USA |
| The Fertility Clinic, Skive | Collaborator | Denmark |
| Statens Serum Institut | Collaborator | Denmark |
| National Institute of Allergy and Infectious Diseases | Collaborator | USA |
Scientific Summary
Therapeutic Trials
In a phase II, multicentre US study, over 400 women with bacterial vaginosis were randomised to receive CTV 05 vaginal capsules or placebo, as an adjunct to antibacterial treatment. Clinical cure rates at 30 days (primary endpoint) did not improve in CTV 05-treated patients. However, vaginal colonisation rates of Lactobacillus crispatus were significantly higher in patients treated with CTV 05, compared with placebo (62 vs 2%) [15] .
In a pilot study involving nine women (aged 18-40 years), vaginal colonisation was evaluated at 1-3 days and 6-8 days following insertion of once CTV 05 capsule intravaginally, twice daily for 3 days. Lactobacillus crispatus was detected in 5/9 women at the first follow-up timepoint and 6/9 women at the second follow-up timepoint. These results were presented with data from studies in pig-tailed macaques [14] .
In data from a phase IIb trial, CTV 05 significantly reduced the recurrence of bacterial vaginosis when compared with placebo (p = 0.01) in 12 weeks in 228 patients. In 79% of patients, L. crispatus was detected at the 12 week visit [6] [8] .
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 16 Aug 2023 | Trial Update | The Fertility Clinic, Skive completes the phase II trial inBacterial vaginosis in Denmark (Vaginal) (NCT05166746) (EudraCT2016-002385-31) Updated 31 Aug 2023 |
| 31 Mar 2023 | Trial Update | Osel completes a phase II trial in Bacterial vaginosis in South Africa (Vaginal) (NCT05022212) Updated 06 Mar 2024 |
| 22 Dec 2021 | Biomarker Update | Biomarkers information updated Updated 24 Dec 2021 |
| 10 May 2021 | Phase Change - II | Phase-II clinical trials in Bacterial vaginosis in South Africa (Vaginal) (NCT05022212) Updated 01 Sep 2021 |
| 03 Feb 2021 | Licensing Status | Osel enters into a clinical trial licensing agreement with Danish Research Consortia (comprising Aarhus University, Skive Hospital and Statens Serum Institut of Denmark) for LACTIN-V for Bacterial vaginosis [1] Updated 05 Feb 2021 |
| 14 May 2020 | Scientific Update | Efficacy data from phase IIb trial in Bacterial vaginosis released by Osel [6] Updated 18 May 2020 |
| 07 Jan 2020 | Active Status Review | CTV 05 is still phase II trial for Bacterial vaginosis in Denmark (Vaginal) (EudraCT2016-002385-31) Updated 07 Jan 2020 |
| 22 Feb 2019 | Trial Update | National Institute of Allergy and Infectious Diseases completes a phase II trial in Bacterial vaginosis in USA (Vaginal) (NCT02766023) Updated 08 Mar 2019 |
| 07 Dec 2017 | Trial Update | The Fertility Clinic Skive initiated the phase II trial in Bacterial vaginosis in Denmark (Vaginal) (NCT05166746) Updated 06 Jan 2022 |
| 17 Nov 2017 | Trial Update | University of Washington completes enrollment in a phase II/III trial for Urinary tract infections (Prevention, Recurrent) in USA (Vaginal) (NCT03151967) Updated 07 Jan 2020 |
| 24 Aug 2017 | Phase Change - II | Phase-II clinical trials in Bacterial vaginosis in Denmark (Vaginal) (EudraCT2016-002385-31) Updated 27 Oct 2017 |
| 11 May 2016 | Phase Change - II | Phase-II clinical trials in Bacterial vaginosis (Prevention, Recurrent) in USA (Vaginal) [7] Updated 13 May 2016 |
| 01 Sep 2015 | Phase Change - II/III | Phase-II/III clinical trials in Urinary tract infections (Prevention, Recurrent) in USA (Vaginal) (NCT03151967) Updated 17 May 2017 |
| 21 Jul 2015 | Active Status Review | Phase II development for Urinary tract infections and Bacterial vaginosis is ongoing Updated 21 Jul 2015 |
| 01 Apr 2012 | Trial Update | Osel completes a phase II trial for Urinary tract infections prevention in USA (NCT00305227) Updated 04 Jul 2012 |
| 11 Feb 2011 | Trial Update | Osel completes enrolment in its phase II trial for Urinary tract infections in USA (NCT00305227) Updated 07 Mar 2011 |
| 09 Jul 2009 | Trial Update | Osel completes a phase II trial in Bacterial vaginosis in USA Updated 14 Aug 2009 |
| 12 Apr 2005 | Phase Change - II | Phase-II clinical trials in Urinary tract infections in USA (Vaginal) Updated 18 Apr 2005 |
| 12 Apr 2005 | Trial Update | Osel has initiated two phase II trials for recurrent bacterial vaginosis and recurrent urinary tract infections Updated 18 Apr 2005 |
| 23 Dec 2004 | Phase Change - I | Phase-I clinical trials in Urinary tract infections in USA (unspecified route) Updated 23 Dec 2004 |
| 19 Jul 2004 | Phase Change - I | Phase-I clinical trials for Bacterial vaginosis in USA (Vaginal) Updated 15 Dec 2004 |
| 19 Jul 2004 | Regulatory Status | Osel Inc. has filed an IND with the US FDA for Urinary tract infections Updated 15 Dec 2004 |
| 30 Jul 2003 | Scientific Update | A study has been added to the Bacterial Infections therapeutic trials section [14] Updated 30 Jul 2003 |
| 13 Feb 2003 | Licensing Status | CTV 05 has been licensed to Osel Updated 13 Feb 2003 |
| 28 Mar 2002 | Scientific Update | A study has been added to the Antibacterials therapeutic trials section [15] Updated 28 Mar 2002 |
| 04 Jul 2001 | Phase Change - II | Phase-II clinical trials for Bacterial vaginosis in USA (Vaginal) Updated 04 Jul 2001 |
| 21 Feb 2000 | Phase Change | Investigation in Bacterial vaginosis in USA (Unknown route) Updated 21 Feb 2000 |
References
-
Osel Obtains Exclusive License from Danish Research Consortia for IP Related to Osels LACTIN-V in Women Undergoing In-Vitro Fertilization.
Media Release -
Lactobacillus Probiotic for Prevention of UTI
ctiprofile -
Phase 2 Placebo-controlled Randomized Trial of LACTIN-V (Lactobacillus Crispatus CTV-05) Among Women at High Risk of HIV Acquisition in Durban, South Africa
ctiprofile -
A double-blind, placebo-controlled multicenter trial on the effect of clindamycin and a live biotherapeutic on the reproductive outcomes of IVF patients with abnormal vaginal microbiota
ctiprofile -
Osels LACTIN-V Enters Clinical Study to Improve the Success Rate of IVF in Women With Imbalanced Vaginal Microbiomes.
Media Release -
Osels Live Biotherapeutic Product Demonstrates Efficacy in Phase 2b Study of Bacterial Vaginosis.
Media Release -
Osel, Inc.s Lead Product LACTIN-V Enters Phase 2b Study to Prevent Recurrence of Bacterial Vaginosis.
Media Release -
Phase II-b Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus Crispatus CTV-05 (LACTIN-V) to Prevent the Recurrence of Bacterial Vaginosis
ctiprofile -
Intravaginal LACTIN-V for Prevention of Recurrent Urinary Tract Infections
ctiprofile -
Osel Announces Private Funding Round, New Board Appointment and Clinical Trial Progress.
Media Release -
Osel Names Levy President, Announces New Board Members, and Start of Phase I Trial.
Media Release -
Osel Initiates Two Phase II Trials for LACTIN-V.
Media Release -
Osel Initiates Two Phase II Trials for LACTIN-V.
Media Release -
Patton DL, Cosgrove Sweeney YT, Antonio MAD, Rabe LK, Hillier SL. Lactobacillus crispatus capsules: single-use safety study in the Macaca nemestrina model. Sex-Transm-Dis 2003;30568-570.
PubMed | CrossRef Fulltext -
The Medicines Company announces results of phase II bacterial vaginosis study.
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