Overview

This trial is active, not recruiting.

Condition hiv-1 infection
Treatment raltegravir and etravirine
Phase phase 2
Sponsor French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Collaborator Merck Sharp & Dohme Corp.
Start date January 2015
End date January 2019
Trial size 160 participants
Trial identifier NCT02212379, 2014-000828-24, ANRS 163 ETRAL

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. Measurement of primary endpoint will be at 48 weeks. Virological success is defined as the absence of 2 consecutive plasma viral load >50 copies/mL within 2 to 4 weeks of a dual raltegravir/etravirin regimen. Raltegravir/etravirine will be considered acceptable if the percentage of patients in virological success at week 48 is significantly above 90 %. Assuming a 95 % virological success rate, by including 160 individuals and considering the strategy to be acceptable if no more than 8 individuals have virological failure; investigators will have a 95 % probability to discard a combination for which efficacy is smaller than 90 % and investigators will select with a power of 80 % the strategy for which the efficacy is above or equal to 95 %. The principal secondary endpoint is the proportion of patients in therapeutic success up to week 48 and 96.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
raltegravir and etravirine
Raltegravir (RAL, ISENTRESS®) 400 mg tablets will be administered as one 400 mg oral tablet PO twice daily (800 mg per day) after a meal. Etravirine (ETR, INTELENCE®) 200 mg tablets will be administered as one 200 mg oral tablet PO twice daily (400 mg per day) after a meal.

Primary Outcomes

Measure
To evaluate the capacity to maintain virological success in HIV-1 infected patients, of at least 45 years of age, with suppressed plasma viremia switching from a boosted PI-containing regimen.
time frame: week 48

Secondary Outcomes

Measure
Tolerability
time frame: From day 0 to week 48 and week 96
Seminal sub-study
time frame: week 48
Immunological outcome
time frame: at each time point from day 0
Evolution of cardiovascular risk
time frame: from day 0 to week 48 and week 96
Evolution of renal function
time frame: from day 0 to week 96
Health-related, quality of life
time frame: from day 0 to week 48 and week 96
Metabolic parameters
time frame: from day 0 to week 48 and week 96
Sub-study: evolution of peripheral and central body fat distribution
time frame: from day 0 to week 48 and week 96
Compliance
time frame: at week-6/ week -4, week 48, and week 96
Virological success
time frame: from day 0 to week 48 and week 96
Treatment interruption
time frame: from day 0 to week 96
Virological failure
time frame: from day 0 to week 96
Virological failure
time frame: at time of virological failure
Virological failure
time frame: between day 0 and week 96
Virological failure: resistance mutations
time frame: between day 0 and week 96
Virological failure: associated factors
time frame: between day 0 and week 96
total HIV-DNA
time frame: from day 0 to week 48 and week 96
Inflammatory parameters
time frame: from day 0 to week 48, and week 96
Sub-study: bone mineral density
time frame: from day 0, to week 48 and week 96

Eligibility Criteria

Male or female participants at least 45 years old.

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 heatlh 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 immunetherapy 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

Additional Information

Official title A Non-comparative Phase II Trial Evaluating the Capacity of the Dual Combination Raltegravir/Etravirine to Maintain Virological Success in HIV-1 Infected Patients of at Least 45 Years of Age With an HIV-RNA Plasma Viremia Below 50 Copies/mL Under a Current Boosted Protease Inhibitor Containing Regimen (ANRS 163 ETRAL)
Principal investigator Christine Katlama, MD
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS).