Capacity of the Dual Combination Raltegravir/Etravirine to Maintain Virological Success in HIV-1 Infected Patients of at Least 45 Years of Age- ANRS 163 ETRAL

• Status: Completed
• Trial end date: 2018-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This multicenter, international, non randomized (single arm), open, phase II trial aims to evaluate the capacity of the dual combination raltegravir/etravirine to maintain virological success in virologically suppressed HIV-1 infected patients, of at least 45 years of age, switching from a boosted PI-containing regimen. Patients will be followed for 96 weeks. The primary endpoint was the proportion of participants with virological success at 48 weeks. Virological success is defined as the absence of 2 consecutive plasma viral load >50 copies/mL within 2 to 4 weeks apart. The study was designed to show an efficacy >90%, assuming a success rate >95%, with a power of 80% and a 5%type-1 error. A total of 160 individuals was required to achieve the objective. The principal secondary endpoint is the proportion of patients in therapeutic success up to week 48 and 96.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases; French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborators: Janssen-Cilag Ltd.; Merck Sharp & Dohme Corp.
• Treatments: Etravirine; Raltegravir Potassium

Criteria

Inclusion Criteria:

• Documented HIV-1 infection

• Age ≥ 45 years

• Naïve to integrase inhibitor and etravirine

• At least 6 months of stable antiretroviral therapy (ART) including a boosted protease inhibitor, whatever the number of combined drugs

• HIV-RNA plasma VL ≤ 50 copies/mL during the last 24 months prior to screening visit (Week-6/Week-4), documented by at least 4 time-points with no more than one blip in HIV-RNA plasma viral load between 51 and 200 copies/mL

• HIV-RNA plasma VL ≤ 50 copies/mL at screening visit (Week-6/Week-4)

• A genotype is available (on amplified DNA at Week-6/Week-4 Visit and/or on RNA in the medical history of the patient) and shows a virus sensitive to ETR OR no genotype is available (amplification failure on DNA at Week-6/Week-4 Visit and no genotype in the medical history of the patient), there are no virological failure on NNRTI in the medical history

• CD4+ lymphocytes > 200 cells/mm3

• Creatinine < 2.5 x ULN

• CPK (Creatine Phospho Kinase) < 6 ULN (Upper Limit of Normal)

• AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase) < 5 ULN

• Hemoglobin > 10 g/dL

• Platelets > 100 000/mm3

• Negative urinary pregnancy test and use of efficient contraception for women of childbearing potential

• For French participants only: subject enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme), article L1121-11 of the Public health code

• Patients with a coverage from a social health

• Signed informed consent

Exclusion Criteria:

• Previous exposure to raltegravir or etravirine

• Presence of any documented integrase inhibitor mutation on DNA genotype at Week-6/Week-4 and/or on RNA in the medical history of the patient

• Positive hepatitis B HBsAg or Positive HBc Ac and negative HBs Ac

• HIV-2 infection

• Active viral hepatitis C requiring a specific treatment during the 24 months of the trial

• Patient with a history of non-compliance or irregular follow-up

• Initiation of a concomitant anti-hypercholesterolemia (e.g. statins) or antidiabetic treatment within the last 3 months prior the screening visit (Week-6 /Week-4)

• Patient using: Clopidogrel (Plavix®), Prasugrel (Effient®), Ticagrelor (Brilinta®), Ticlopidine (Ticlid®), Flurbiprofen (Antadys® - Cebutid®), Rifampin (Rifampicin® - Rifadin® - RofactMC - Rifater®), Rifapentine (Priftin®), St John's wort, Carbamazepine (Tegretol®), Phenobarbital, Phenytoin (Dilantin®),Avanafil (Stendra™), Triazolam (Halcion®)

• Concomitant treatment using interferon, interleukins or any other immunotherapy 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 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