Overview

This trial is active, not recruiting.

Condition hiv-1 infection
Treatments dolutegravir (tivicay®) - phase 1, lamivudine (epivir®) - phase 2, dolutegravir (tivicay®) - phase 2
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 ViiV Healthcare
Start date September 2015
End date April 2017
Trial size 110 participants
Trial identifier NCT02527096, 2015-001492-44, ANRS 167 Lamidol

Summary

The principal objective is to evaluate the antiviral efficacy of 48 weeks treatment with the two-drugs combination dolutegravir(Tivicay®) and lamivudine(TEpivir®) in HIV-1 infected patients virologically suppressed with triple HAART.

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)
dolutegravir (tivicay®) - phase 1
• Phase 1 (8 weeks) : switch of the third agent with dolutegravir(Tivicay®) 50 mg once a day.
lamivudine (epivir®) - phase 2
• Phase 2 (48 weeks): combination with lamivudine (Epivir®) 300 mg once a day + dolutegravir (Tivicay®) 50 mg once a day. Only participants with plasma HIV RNA ≤ 50 cp/mL at Week 8 will continue on phase 2.
dolutegravir (tivicay®) - phase 2
• Phase 2 (48 weeks): combination with lamivudine (Epivir®) 300 mg once a day + dolutegravir (Tivicay®) 50 mg once a day. Only participants with plasma HIV RNA ≤ 50 cp/mL at Week 8 will continue on phase 2.

Primary Outcomes

Measure
Virological success without any intercurrent event leading to interrupt the strategy of the trial (analysis)
time frame: from week 8 to week 56 (± 4 weeks)

Secondary Outcomes

Measure
Evolution of CD4 and CD8 lymphocytes count (analysis)
time frame: from week 8 to week 32 and week 56
Percentage of participants who discontinued the strategy of the trial for toxicity or with adverse event of grade 3 or 4 (analysis)
time frame: week 56
Profile of resistance mutations in plasma in case of virological failure
time frame: week 56
Percentage of participants with plasma HIV RNA < 1 cp/mL
time frame: Day 0, week 8, week 32 and week 56
Influence of total DNA on the occurrence of virological failure or blip
time frame: from Day 0 to week 56
Measure of concentrations of dolutegravir(Tivicay®) and lamivudine(Epivir®) in case of virological failure or with a blip
time frame: week 56
Measure of adherence to treatment (self-reported)
time frame: Day 0, week 4, week 8, week 32 and week 56
Measure of quality of life (self-reported)
time frame: Day 0, week 8 and week 56
Comparison of Medico-economic substudy (analysis)
time frame: week 56
Sperm substudy measure of concentration
time frame: Week 8 and week 32

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria

  • HIV-1 infected patient
  • Age ≥ 18 years
  • CD4 cell count nadir > 200/mm3
  • Genotype on pre-HAART interpreted with the last version of the ANRS AC11 resistance group's algorithm which presents:
    • no major mutation on protease among: D30N, V32I, M46I/L, I47A/V, G48V, I50L/V, 154M/L, L76V, V82A/F/T/S, I84V, N88D/S, L90M,- no mutation on RT (except the mutation A98S if the patient is not infected by the virus subtype C),
    • no mutation on integrase (if the genotype is available),
  • First-line treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, 1 NNRTI or 1 INI). The initial treatment may have changed a maximum of two times but only once for toxicity (changes such Epivir / Ziagen to Kivexa, are not considered as a change of treatment). However, treatment has to be unchanged in the last 6 months
  • Plasma HIV RNA ≤ 50 copies/mL for ≥ 2 years with at least 2 viral load determinations per year. Blips (HIV viral load between 50 and 200 copies/mL but ≤ 50 copies/mL on control sample) are allowed except in the last 6 months. The total number of blips must not exceed 3 in the last 2 years
  • Negative Hepatitis Bs Antigen
  • Effective contraception for women of childbearing potential
  • Informed consent form signed by patient and investigator
  • Patient enrolled in or a beneficiary of a Social Security programme (State Medical Aid ("Aide Médicale d'Etat" AME in France) is not a Social Security programme)

Exclusion Criteria

  • HIV-2 infection
  • Positive HBc Ac isolated
  • Hepatitis B Virus (HBV) co-infected patients (positive Hepatitis Bs Ag at inclusion)
  • Chronic hepatitis C currently treated or needing therapy in the next 12 months
  • History of HIV-associated neurocognitive disorders
  • Current pregnancy or breastfeeding
  • No effective contraception for the women of childbearing
  • Previous treatment with chemotherapy (except bleomycin on Kaposi disease's treatment) or immunotherapy
  • Grade > 2 abnormality for usual biological parameters (liver function tests, blood cell count)
  • ALT(Alanine Aminotransferase) ≥ 5 x upper limit of normal value (ULN) or AST (Aspartate Aminotransferase) ≥ 3 x ULN and bilirubinemia ≥ 1.5 x ULN (with 35% direct bilirubinemia)
  • Unstable liver disease (ascitis, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice)
  • Known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Creatininemia clearance below 50 mL/min (Cockroft-Gault method)
  • History or presence of allergy to the trial drugs or their components
  • Severe hepatic insufficiency (Child Pugh Class C)
  • Patients participating in another clinical trial including an exclusion period that is still in force during the screening phase
  • Patients under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties) or under legal guardianship.

Additional Information

Official title A Pilot Trial Evaluating Maintenance Therapy With Lamivudine(Epivir®) and Dolutegravir(Tivicay®) in Human Immunodeficiency Virus 1 (HIV-1) Infected Patients Virologically Suppressed With Triple HAART - ANRS 167 Lamidol
Principal investigator Véronique JOLY, MD
Description Secondary objectives: The following parameters will be evaluated : - Evolution of CD4 cells and CD8 cells - Tolerance to treatment - Emergence of resistance mutations at time of virological failure - HIV viral load measured with ultrasensitive assay (threshold 1 copy/mL) at Day 0, Week 8, Week 32 and Week 56 - Influence of total DNA at Day 0 on the occurrence of virological failure or blip - Plasma levels of dolutegravir(Tivicay®) and lamivudine in participants with virological failure - Adherence to treatment - Quality of life - Medico-economic aspects - Dolutegravir(Tivicay®) and Nucleosidic Reverse Transcriptase Inhibitors (NRTIs) levels, and HIV viral load in semen in a subgroup of 20 participants. Methodology: Pilot trial, multicentric, national, prospective, no randomized and no comparative.
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).