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

NCT ID: NCT02212379

Last Updated: 2021-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-04-30

Brief 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.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

raltegravir and etravirine

Group Type: EXPERIMENTAL

raltegravir and etravirine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine Katlama, MD

Role: PRINCIPAL_INVESTIGATOR

Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

Jacques Reynes, MD

Role: STUDY_CHAIR

Département des Maladies Infectieuses et Tropicales Hôpital Gui de Chauliac, CHU de Montpellier France

Dominique Costagliola, PhD

Role: STUDY_DIRECTOR

Inserm UMR S 1136 Université Pierre et Marie Curie Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Paris, France

Locations

Hôpital Avicenne

Bobigny, , France

Hôpital Jean Verdier

Bondy, , France

Hôpital Saint André

Bordeaux, , France

Hôpital Bicêtre

Le Kremlin-Bicêtre, , France

Hôpital Croix Rousse

Lyon, , France

Hôpital Sainte marguerite

Marseille, , France

Hôpital Gui de Chauliac

Montpellier, , France

CHU Hôtel Dieu

Nantes, , France

Hôpital de l'Archet

Nice, , France

Hôpital Saint Louis

Paris, , France

Hôpital Pitié-Salpétrière

Paris, , France

Hôpital Cochin

Paris, , France

Hôpital Necker

Paris, , France

Hôpital Bichat Claude Bernard

Paris, , France

Hôpital Européen Georges Pompidou

Paris, , France

Hôpital Bretonneau

Tours, , France

Hospital de Bellvitge

Barcelona, , Spain

Hospital de la santa Creu i San Pau

Barcelona, , Spain

Hospital Clinic

Barcelona, , Spain

Countries

France; Spain

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form: Study protocol, Statistical Analysis

View Document

Document Type: Informed Consent Form: Informed Consent Form

View Document

Related Links

http://www.anrs.fr/

Related Info

Other Identifiers

ANRS 163 ETRAL

Identifier Type: OTHER

Identifier Source: secondary_id

2014-000828-24

Identifier Type: -

Identifier Source: org_study_id