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

NCT04513626 | Recruiting Phase 2 DMC

• 1 other identifier: CREPATS 010
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (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

  Measure of plasma viral load assessed by RNA quantification using COBA 6800 system (Roche)

  48 weeks

Study Arms (2)

Delayed switch

OTHER

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

EXPERIMENTAL

Immediate switch to doravirine/raltegravir

Drug: DORAVIRINE 100 MG [Pifeltro]

Interventions

DORAVIRINE 100 MG [Pifeltro] DRUG

Immediate switch

Also known as: Raltegravir 600 Mg x 2 [Isentress]

Delayed switch; Immediate switch

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Pregnant women or breastfeeding women

Sponsors & Collaborators

• Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida: lead

Study Sites (1)

Christine KATLAMA

Paris, Île-de-France Region, 75013, France

RECRUITING

MeSH Terms

Conditions

HIV Infections

Interventions

doravirine; Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christine Katlama, MD

  Pitie-Salpetriere Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yasmine Dudoit

CONTACT

33142164181; yasmine.dudoit@aphp.fr

Christine Katlama, MD

CONTACT

33142160142; christine.katlama@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 14, 2020
• Study Start: September 15, 2020
• Primary Completion: October 30, 2025
• Study Completion: October 30, 2025
• Last Updated: January 10, 2025

Record last verified: 2025-01

Locations

FR (1)