Ignite Creation Date:
2025-12-24 @ 2:24 PM
Ignite Modification Date:
2026-02-25 @ 5:53 PM
Study NCT ID:
NCT01905059
Status:
COMPLETED
Last Update Posted:
2017-07-21
First Post:
2013-07-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Evaluation of a Maintenance Strategy With Protease Inhibitors With or Without Lamivudine in Virologically Suppressed HIV Patients on Second Line Antiretroviral Treatment in Africa
Sponsor:
ANRS, Emerging Infectious Diseases
Organization:
Study Overview
Official Title:
Multicenter, International, Prospective, Phase III, Randomized, Superiority Trial Comparing Two Maintenance Strategies With Mono or Bi-therapy of Protease Inhibitors With or Without Lamivudine in Virologically Suppressed HIV Patients on Second Line Antiretroviral Treatment Over a Period of 96 Weeks in Africa (Dakar, Bobo Dioulasso, Yaounde)
Status:
COMPLETED
Status Verified Date:
2017-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MOBIDIP
Brief Summary:
Multicenter, randomized, superiority trial to evaluate efficacy of a mono or bi-therapy of protease inhibitors with or without lamivudine over a period of 96 weeks. The primary outcome will be the failure rate at 96 weeks. This study will include 260 participants, former participants of the 2LADY trial. It will be carried out in Yaoundé, Bobo Dioulasso and Dakar.
Detailed Description:
Justification: The interest of treating HIV infection with a single molecule has been clear for a long time. Many clinical trials have been testing the efficacy of such a strategy, mainly using a boosted protease inhibitor (PI). Despite the remaining doubts about low level viremia, viral control in reservoirs, durability of the effect, the trials showed attractive results with an absolute increase in the risk of virological failure between 2% and 13% compared to the standard of care and a possible decrease in costs and toxicity.
In resource-limited countries the interest of treatment simplification is even more important: decrease in costs, toxicity (often poorly monitored), number of pills taken per day, etc. In addition, for patients in second line for whom some kind of resistance to NRTI is highly probable, the interruption of the second line NRTI could help to avoid the accumulation of mutations in the RT in the presence of residual low level replication, sparing future treatment options.
The 184 mutation of the retro-transcriptase which causes resistance to lamivudine/emtricitabine seems to hinder viral replication. The persistence of this mutation could eventually facilitate the action of PI monotherapy while protecting patients from further mutations. The choice of viral load (VL) threshold for the diagnosis of failure in resource-limited countries is not easy, the 2LADY trial used in clinical practice, the threshold of 1000 copies/ml which allows genotyping for evidence of mutations. This value will probably be selected as a reference value by the WHO in its next recommendations. To minimize the risk of viral escape and the development of resistances in the MOBIDIP study the threshold of 200 copies/ml has been chosen for the switch to monotherapy and of 500 copies/ml for the definition of failure.
Principal objective: To evaluate the failure rate at 96 weeks of a PI monotherapy with or without lamivudine, in HIV positive patients on second line treatment (ART) for at least 48 weeks, and with a VL of less than 200 copies/ml in Africa (Yaoundé, Bobo Dioulasso, Dakar).
Specific objectives: To evaluate:
* viral efficacy at a threshold of 50 copies/ml at 48 and 96 weeks,
* failure rate at 500 copies/ml after 24 weeks from the reintroduction of NRTI backbone in case of monotherapy failure,
* clinical and immunological outcomes,
* development of mutations,
* tolerance and impact on metabolic profile and
* neuro-cognitive disorders,
* adherence
Methods: multicenter, randomized, superiority trial to evaluate efficacy of a mono or bi-therapy of protease inhibitors with or without lamivudine over a period of 96 weeks. The primary outcome will be the failure rate at 96 weeks. Failure is defined as: 1) viral load ≥500 copies/ml, 2) reintroduction of NRTI backbone, 3) interruption of the PI. A sample of 260 participants is planned.
Schedule: After approval by national Ethical committees and national authorities, patients followed in 2LADY trial for at least 48 weeks, and presenting the eligibility criteria, will stop their NRTI backbone and be randomized (over 6 months) to add or not lamivudine to their PI monotherapy. All patients will be followed for 96 weeks. In case of viral load above 500 copies/ml during the study, the original NRTI backbone will be re-introduced and the patient will be followed for an extra 24 weeks to verify viral response. The complete trial is due to last 3 years.
Expected results: This study will allow the validation of a maintenance strategy for patients in second line ART less expensive and toxic. In addition results could be used to guide clinical practice for physicians in resources poor countries
In march 2016 an interim analysis asked by the DSMB showed increased risk of failure in the monotherpay arm and the arm was stopped. Participant are switched on standard second line triple therapy and followed until Week 96. Participant on dual therapy continue their follow up. Comparative analysis are planned for data on week 60 visit (last visit with all participants on the randomized treatment).
In resource-limited countries the interest of treatment simplification is even more important: decrease in costs, toxicity (often poorly monitored), number of pills taken per day, etc. In addition, for patients in second line for whom some kind of resistance to NRTI is highly probable, the interruption of the second line NRTI could help to avoid the accumulation of mutations in the RT in the presence of residual low level replication, sparing future treatment options.
The 184 mutation of the retro-transcriptase which causes resistance to lamivudine/emtricitabine seems to hinder viral replication. The persistence of this mutation could eventually facilitate the action of PI monotherapy while protecting patients from further mutations. The choice of viral load (VL) threshold for the diagnosis of failure in resource-limited countries is not easy, the 2LADY trial used in clinical practice, the threshold of 1000 copies/ml which allows genotyping for evidence of mutations. This value will probably be selected as a reference value by the WHO in its next recommendations. To minimize the risk of viral escape and the development of resistances in the MOBIDIP study the threshold of 200 copies/ml has been chosen for the switch to monotherapy and of 500 copies/ml for the definition of failure.
Principal objective: To evaluate the failure rate at 96 weeks of a PI monotherapy with or without lamivudine, in HIV positive patients on second line treatment (ART) for at least 48 weeks, and with a VL of less than 200 copies/ml in Africa (Yaoundé, Bobo Dioulasso, Dakar).
Specific objectives: To evaluate:
* viral efficacy at a threshold of 50 copies/ml at 48 and 96 weeks,
* failure rate at 500 copies/ml after 24 weeks from the reintroduction of NRTI backbone in case of monotherapy failure,
* clinical and immunological outcomes,
* development of mutations,
* tolerance and impact on metabolic profile and
* neuro-cognitive disorders,
* adherence
Methods: multicenter, randomized, superiority trial to evaluate efficacy of a mono or bi-therapy of protease inhibitors with or without lamivudine over a period of 96 weeks. The primary outcome will be the failure rate at 96 weeks. Failure is defined as: 1) viral load ≥500 copies/ml, 2) reintroduction of NRTI backbone, 3) interruption of the PI. A sample of 260 participants is planned.
Schedule: After approval by national Ethical committees and national authorities, patients followed in 2LADY trial for at least 48 weeks, and presenting the eligibility criteria, will stop their NRTI backbone and be randomized (over 6 months) to add or not lamivudine to their PI monotherapy. All patients will be followed for 96 weeks. In case of viral load above 500 copies/ml during the study, the original NRTI backbone will be re-introduced and the patient will be followed for an extra 24 weeks to verify viral response. The complete trial is due to last 3 years.
Expected results: This study will allow the validation of a maintenance strategy for patients in second line ART less expensive and toxic. In addition results could be used to guide clinical practice for physicians in resources poor countries
In march 2016 an interim analysis asked by the DSMB showed increased risk of failure in the monotherpay arm and the arm was stopped. Participant are switched on standard second line triple therapy and followed until Week 96. Participant on dual therapy continue their follow up. Comparative analysis are planned for data on week 60 visit (last visit with all participants on the randomized treatment).
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: