- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02212379
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
Dual Therapy Combining Raltegravir With Etravirine Maintains a High Level of Viral Suppression Over 96 Weeks in Long-term Experienced HIV-infected Individuals Over 45 Years on a PI-based Regimen: Results From the Phase II ANRS 163 ETRAL Study
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
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Bobigny, France, 93000
- Hôpital Avicenne
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Bondy, France, 93140
- Hôpital Jean Verdier
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Bordeaux, France, 33076
- Hôpital Saint André
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Le Kremlin Bicêtre, France, 94275
- Hopital Bicetre
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Lyon, France, 69317
- Hopital Croix Rousse
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Marseille, France, 13009
- Hôpital Sainte Marguerite
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Montpellier, France, 34000
- Hopital Gui de Chauliac
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Nantes, France, 44093
- CHU Hotel Dieu
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Nice, France, 06202
- Hopital de l'Archet
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Paris, France, 75010
- Hopital Saint Louis
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Paris, France, 75014
- Hopital Cochin
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Paris, France, 75908
- Hopital Europeen Georges Pompidou
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Paris, France, 75018
- Hopital Bichat Claude Bernard
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Paris, France, 75015
- Hopital Necker
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Paris, France, 75013
- Hôpital Pitié-Salpétrière
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Tours, France, 37044
- Hôpital Bretonneau
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-
-
-
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Barcelona, Spain, 08036
- Hospital Clínic
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Barcelona, Spain, 08000
- Hospital de Bellvitge
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Barcelona, Spain, 08025
- Hospital de la Santa Creu i San Pau
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96
Time Frame: at week48 and at week 96
|
Virological success is defined as the absence of 2 consecutive plasma viral loads (VL) > 50 copies/mL within 2 to 4 weeks of a dual raltegravir/etravirine regimen. The proportion of patients who maintained viral suppression under raltegravir plus etravirine was 99.4% (95% confidence interval (95% CI:95.6 -99.9) at week 48 and 98.7% (95% CI: 95.0 -99.7) at week 96 |
at week48 and at week 96
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Patients With Therapeutic Success at Week 48 and Week 96
Time Frame: weeks 48 and 96
|
Therapeutic success was defined as the absence of virological failure (i.e. 2 consecutive plasma viral loads (VL) > 50 copies/mL within 2 to 4 weeks) and the absence of treatment interruption due to adverse event judged by DSMB as related to the study treatment or procedure
|
weeks 48 and 96
|
Percentage of Patients With Trial Treatment Interruption at Week 48 and Week 96
Time Frame: weeks 48 and 96
|
weeks 48 and 96
|
|
Percentage of Patients With With Grade Virological Failure (HIV-RNA Plasma VL Between 51 and 200 Copies/mL)
Time Frame: weeks 48 and 96
|
weeks 48 and 96
|
|
Median Time of Virological Failure
Time Frame: week 96
|
Time between the date of the study treatment initiation and the date of virological failure
|
week 96
|
Percentage of Patients With High Grade of Virological Failure Defined as HIV RNA > 200 Copies/mL
Time Frame: weeks 48 and 96
|
weeks 48 and 96
|
|
Number of Patients With RAL and/or ETR Resistance Mutations Among Those With Virological Failure
Time Frame: week 96
|
week 96
|
|
Factors Associated With the Occurrence of Plasma HIV-RNA Viral Load > 50 Copies/mL
Time Frame: week 96
|
week 96
|
|
Evolution of Total Cell-associated HIV-DNA
Time Frame: from day 0 to week 48 and week 96
|
from day 0 to week 48 and week 96
|
|
Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio
Time Frame: from day 0 to week 48 and week 96
|
from day 0 to week 48 and week 96
|
|
Number of Participants Experiencing Adverse Events and Effects
Time Frame: From day 0 to week 48 and week 96
|
Number of all clinical and biological adverse events effects.
Number of grade 3 or 4 clinical and biological adverse events and effects.
|
From day 0 to week 48 and week 96
|
Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia)
Time Frame: from day 0 to week 96
|
from day 0 to week 96
|
|
Evolution of the Calibrated 5-year Framingham Risk Score
Time Frame: from day 0 to week 48 and at week 96
|
The Framingham risk score is expressed as a percentage. Higher scores mean a worse outcome and lower scores mean better outcome. Median percent change expressed as median (interquartile range (IQR)) |
from day 0 to week 48 and at week 96
|
Percent Change of Renal Function
Time Frame: from day 0 to week 96
|
Percent change of the estimated Glomerular Filtration Rate (eGFR) calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Calculator) formula
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from day 0 to week 96
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Evolution of Body Fat Distribution From Day 0 to W96 (DXA Scan Sub-study, 80 Patients)
Time Frame: from day 0 to week 96
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Evolution of total fat mass, limb fat and trunk fat from day 0 to week 96
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from day 0 to week 96
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Sub-study: Bone Mineral Density
Time Frame: from day 0, to week 48 and week 96
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• Evolution of bone mineral density (BMD) measured by DXA scans (DXA scan sub-study, 81 patients)
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from day 0, to week 48 and week 96
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Percentage of Participants With Detectable Seminal HIV-RNA Viral Load at Week 48
Time Frame: week 48
|
• Assessment of HIV-RNA viral load in human male genital compartment (20 patients) at week 48
|
week 48
|
Inflammatory Parameters
Time Frame: from day 0 to week 96
|
• Evolution of the inflammation markers (IL-6hs, sCD14, sCD163, D-Dimers, IP-10, IgG, CRPus and insulin) on frozen plasma aliquots
|
from day 0 to week 96
|
Percentage of Participants Reporting a Very Good or an Excellent Quality of Life at Day 0, Weeks 48 and 96
Time Frame: day 0 and weeks 48 and 96
|
day 0 and weeks 48 and 96
|
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Percentage of Participants Compliant With Treatment Program.
Time Frame: at week 0, week 48, and week 96
|
The compliance rate was estimated as the number of pills consumed (recorded using the self-reported 90 questionnaire) divided by the number of pills theoretically consumed, classified as low (80%), medium (80%-95%) or high (95%).
|
at week 0, week 48, and week 96
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Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots
Time Frame: from day 0, to week 48
|
We measured the Anti-mullerian Hormone (AMH) level to evaluate the ovarian reserve (from D0 to W48)
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from day 0, to week 48
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Evolution of the Level of MCP1 From D0 to W48 on Frozen Samples
Time Frame: from day 0, to week 48
|
from day 0, to week 48
|
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Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96
Time Frame: from day 0, to week 96
|
Metabolic markers measures are total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides. Inflammatory and innate immune activation markers measures are: IL-6hs, sCD14, sCD163, D-Dimers, IP-10, IgG, hsCRP and Insulin. Ovarian reserve measure is AMH |
from day 0, to week 96
|
Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status
Time Frame: from day 0, to week 96
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BMI, Hip circumference, Waist circumference, waist/hip ratio, Limb fat, Trunk fat, Total fat, Limb lean, Trunk lean, and Total lean
|
from day 0, to week 96
|
Collaborators and Investigators
Investigators
- Principal Investigator: Christine Katlama, MD, Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- Study Chair: Jacques Reynes, MD, Département des Maladies Infectieuses et Tropicales Hôpital Gui de Chauliac, CHU de Montpellier France
- Study Director: Dominique Costagliola, PhD, Inserm UMR S 1136 Université Pierre et Marie Curie Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Paris, France
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2014-000828-24
- ANRS 163 ETRAL (Other Identifier: ANRS)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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