Clinical Trials

MainTitle

A Trial Evaluating Maintenance Therapy With Lamivudine (Epivir®) and Dolutegravir (Tivicay®) in Human Immunodeficiency Virus 1 (HIV-1) Infected Patients Virologically Suppressed With Triple Highly Active Antiretroviral Therapy (HAART) (ANRS 167 Lamidol)

This study has been completed
Sponsor
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Collaborator
ViiV Healthcare

Information provided by (Responsible Party)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier
NCT02527096

First received: August 6, 2015
Last updated: August 18, 2017
Last Verified: August 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV-1 Infection

Drug : dolutegravir (Tivicay®) - Phase 1
Drug : lamivudine (Epivir®) - Phase 2
Drug : dolutegravir (Tivicay®) - Phase 2
Phase 2

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures

  • 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) ]
    Virological failure is defined by plasma HIV RNA > 50 cp/mL on 2 following samples at 2 to 4 weeks apart.
Secondary Outcome Measures:
  • Evolution of CD4 and CD8 lymphocytes count (analysis) [ Time Frame: from week 8 to week 32 and week 56 ]
    Evaluation was calculated as the CD4 count at the corresponding week minus the baseline CD4 count
  • 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 ]
    Influence of total DNA at Day 0 on the occurrence of virological failure or blip
  • 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 ]
    Evaluation of medico-economic aspects. Evaluate the direct medical cost related to dolutegravir and lamivudine versus the cost of the previous treatment.
  • Sperm substudy measure of concentration [ Time Frame: Week 8 and week 32 ]
    Measure of concentrations of dolutegravir and NRTI, and HIV RNA in semen at Week 8 and Week 32 in a subgroup of 20 participants

Enrollment: 110
Study Start Date: September 17, 2015
Study Completion Date: March 2017
Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: dolutegravir(Tivicay®) and lamivudine(Epivir®)

Drug: dolutegravir (Tivicay®) - Phase 1

• Phase 1 (8 weeks) : switch of the third agent with dolutegravir(Tivicay®) 50 mg once a day.

Drug: 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.

Drug: 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.

Detailed 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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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.

contacts and locations

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT02527096

Locations

France
Hôpital Avicenne
Bobigny, France, 93009
Hôpital Saint-André
Bordeaux, France, 33000
Hôpital Gabriel Montpied
Clermont-Ferrand, France, 63003
Hôpital du Bocage
Dijon, France, 21079
Hôpital Pierre Zobda-Quitman
Fort de France, France, 97261
Hôpial Bicêtre
Le Kremelin Bicêtre, France, 94270
Hôpital Gui de Chaudiac
Montpellier, France, 34295
Hôpital de l'Hotel Dieu
Nantes, France, 44093
Hôpital Saint-Louis
Paris, France, 75010
Hôpital Saint-Antoine
Paris, France, 75012
Hôpital Pitié-Salpêtrière
Paris, France, 75013
Hôpital Necker
Paris, France, 75015
Hôpital Bichat
Paris, France, 75018
Centre hospitalier de Pernignan
Perpignan, France, 66046
Hôpital Pontchaillou
Rennes, France, 35033
Hôpital Purpan
Toulouse, France, 31059
Hôpital Gustave Dron
Tourcoing, France, 59208
Hôpital Bretonneau
Tours, France, 37044

Sponsors and Collaborators

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ViiV Healthcare

Investigators

Principal Investigator: Véronique JOLY, MD Service des Maladies Infectieuses, Hôpital Bichat-Claude Bernard, Paris
Study Chair: Yazdan YAZDANPANAH, MD Service des Maladies Infectieuses, Hôpital Bichat-Claude Bernard
Study Director: Roland LANDMAN, MD Institut de Médecine et Epidémiologie Appliquée (IMEA), Paris
More Information

More Information

Additional Information:

Related Info

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)  
ClinicalTrials.gov Identifier: NCT02527096   History of Changes  
Other Study ID Numbers: ANRS 167 Lamidol  
  2015-001492-44  
Study First Received: August 6, 2015  
Last Updated: August 18, 2017  

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

dolutegravir(Tivicay®)
lamivudine(Epivir®)
HIV-1
efficacy
safety

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lamivudine
Dolutegravir

ClinicalTrials.gov processed this data on May 24, 2020
This information is provided by ClinicalTrials.gov.