HIV-1 Infected Patients, Phase II Trial, Dual Combination Doravirine/Raltegravir Open Label (DORAL)
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|ClinicalTrials.gov Identifier: NCT04513626|
Recruitment Status : Not yet recruiting
First Posted : August 14, 2020
Last Update Posted : August 18, 2020
The objective of antiretroviral therapy (ART) is the maintenance of HIV viral suppression, the optimal condition to prevent disease progression, to optimize immune restoration, to prevent the development of viral resistance and to reduce viral transmission. Antiretroviral therapy has to be maintained long life over decades in the absence of strategies for HIV cure. This is why the long-term cumulative toxicity of ARV drugs is a major issue. Indeed as a consequence of potent ART strategies, in 2011 over 88% of patients on ART in the French Hospital database (ANRS CO4 FHDH) achieved viral suppression with HIV-RNA plasma viral load < 50 copies/mL and nearly 60% had CD4 > 500/mm3. As a consequence of massive reduction of mortality and morbidity related to HIV, infected patients are aging with 40% of patients over 50 years of age in the ANRS CO4 FHDH.
The current standard-of-care for antiretroviral therapy consists in a triple drug combination with two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase inhibitor (INSTI). NRTIs and PIs have been associated to cumulative long-term toxicity such as bone and renal disorders related to tenofovir and increased cardio-vascular risk with PIs. In general population, aging is associated with well-known comorbidities such as bone demineralization, increased incidence of cardio or cerebrovascular disease, diabetes, renal dysfunction. HIV infected patients are at a greater risk for such abnormalities. Another crucial concern is the high probability of drug-drug interactions in HIV-infected patients, between ART and comedications.
Alternative strategies are needed, which must address the following questions: how to maintain the control of HIV viral replication while minimizing the occurrence of long-term clinical and metabolic complications, and minimizing the risk of drug-drug interactions?
This study is an open label, randomized, switch study over 96 weeks in which virally suppressed patients on a stable combined ART regimen will be randomized (2:1) to an immediate switch to doravirine/raltegravir (immediate switch group) or to the maintaining of their current ART followed by a switch to doravirine/raltegravir at W48 (delayed switch group). Patients will be followed during 96 weeks.
|Condition or disease||Intervention/treatment||Phase|
|HIV Infections||Drug: DORAVIRINE 100 MG [Pifeltro]||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
This study is an open label, randomized, switch study, over 96 weeks, in which virally suppressed patients on a stable combined ART regimen will be randomized (2:1) to an immediate switch to doravirine/raltegravir (immediate switch group) or to the maintaining of their current ART followed by a switch to doravirine/raltegravir at W48 (delayed switch group). Patients will be followed during 96 weeks.
The randomization will be stratified on gender and antiretroviral regimen at inclusion (Dual therapy or more).
|Masking:||None (Open Label)|
|Official Title:||A Randomized Comparative Phase II Trial Evaluating the Capacity of the Dual Combination Doravirine/Raltegravir to Maintain Virological Success in HIV-1 Infected Patients With an HIV-RNA Plasma Viremia Below 50 Copies/mL Under a Current Antiretroviral Regimen|
|Estimated Study Start Date :||September 15, 2020|
|Estimated Primary Completion Date :||October 30, 2021|
|Estimated Study Completion Date :||October 30, 2022|
the maintaining of their current ART followed by a switch to doravirine/raltegravir at W48 (delayed switch group).
Drug: DORAVIRINE 100 MG [Pifeltro]
Other Name: Raltegravir 600 Mg x 2 [Isentress]
- Measure the virological efficacy at week 48 of once daily doravirine plus raltegravir dual therapy to assess the effectiveness of the dual therapy DORAL to maintain the virological success to W48 [ Time Frame: 48 weeks ]Measure of plasma viral load assessed by RNA quantification using COBA 6800 system (Roche)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04513626
|Contact: Yasmine Dudoitfirstname.lastname@example.org|
|Contact: Christine Katlama, MDemail@example.com|
|Principal Investigator:||Christine Katlama, MD||Pitie-Salpetriere Hospital|