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HIV-1 Infected Patients, Phase II Trial, Dual Combination Doravirine/Raltegravir Open Label (DORAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04513626
Recruitment Status : Not yet recruiting
First Posted : August 14, 2020
Last Update Posted : August 18, 2020
Sponsor:
Information provided by (Responsible Party):
Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
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)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Delayed switch
the maintaining of their current ART followed by a switch to doravirine/raltegravir at W48 (delayed switch group).
Drug: DORAVIRINE 100 MG [Pifeltro]
Immediate switch
Other Name: Raltegravir 600 Mg x 2 [Isentress]




Primary Outcome Measures :
  1. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • Patients with HIV-1 documented infection
  • CD4 ≥ 200/mm3
  • On stable combined ART regimen with at least 2 drugs for at least 6 months
  • HIV-RNA plasma VL ≤ 50 copies/mL during the last 12 months prior to screening visit (W-6/W-4), documented by at least 2 time-points with no more than one blip (defined as one HIV-RNA plasma VL between 51 and 200 copies/mL followed by one HIV-RNA plasma VL ≤ 50 copies/mL)
  • Naive to doravirine
  • Absence of resistance to doravirine* and/or raltegravir**(see list mutations below)

    • on all HIV-genotypes with available RT and integrase gene sequences allowing resistance interpretation in case of previous virological failure
    • or on DNA genotype performed at screening if HIV genotype is not available in case of prior virological failure.
  • Signed informed consent form.
  • Patient affiliated to a social insurance regimen. For French patients only: subject enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme).

    • Mutations associated to doravirine resistance are: V106A/M, Y188L, G190E/S, M230L, F227C, at least 2 among: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y

      • Mutations associated to raltegravir resistance are: T66A/K, E92Q, G118R, F121Y, G140A/S Y143A/C/G/H/R/S, Q148E/G/H/K/R, V151L, N155H/S/T, E157Q, S230R, R263K, L74 F/I + V75I.

Exclusion Criteria:

  • Absence of RT and INI HIV sequence available (past genotypes or failure of amplification of DNA at screening)
  • HBV co-infection
  • Hemoglobin <9 g/dL
  • Platelets <80,000/mm3
  • Creatinine clearance <60 mL/min (MDRD)
  • AST or ALT ≥5N
  • Concomitant DAA for anti-HCV therapy
  • Any severe concomitant illness
  • Any drug with potential drug-drug interaction with doravirine
  • Concomitant treatment using interferon, interleukins or any other immune-therapy or chemotherapy
  • Concomitant prophylactic or curative treatment for an opportunistic infection
  • All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with trial protocol compliance, adherence and/or trial treatment tolerance
  • Subjects under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship
  • Subjects participating in another clinical trial evaluating different therapies and including an exclusion period that is still in force during the screening phase
  • Pregnant women or breastfeeding women

Information from the National Library of Medicine

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


Contacts
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Contact: Yasmine Dudoit 33142164181 yasmine.dudoit@aphp.fr
Contact: Christine Katlama, MD 33142160142 christine.katlama@aphp.fr

Locations
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France
Christine KATLAMA
Paris, Ile De France, France, 75013
Contact: Yasmine Dudoit    33142164181    yasmine.dudoit@aphp.fr   
Contact: Christine Katlama, MD    33142160142    christine.katlama@aphp.fr   
Sponsors and Collaborators
Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida
Investigators
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Principal Investigator: Christine Katlama, MD Pitie-Salpetriere Hospital
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Responsible Party: Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida
ClinicalTrials.gov Identifier: NCT04513626    
Other Study ID Numbers: CREPATS 010
First Posted: August 14, 2020    Key Record Dates
Last Update Posted: August 18, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action