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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)

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ClinicalTrials.gov Identifier: NCT02527096
Recruitment Status : Completed
First Posted : August 18, 2015
Last Update Posted : August 22, 2017
Sponsor:
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)

Brief 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.

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: dolutegravir (Tivicay®) - Phase 1 Drug: lamivudine (Epivir®) - Phase 2 Drug: dolutegravir (Tivicay®) - Phase 2 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
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
Actual Study Start Date : September 17, 2015
Actual Primary Completion Date : March 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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 ]
  3. Profile of resistance mutations in plasma in case of virological failure [ Time Frame: week 56 ]
  4. Percentage of participants with plasma HIV RNA < 1 cp/mL [ Time Frame: Day 0, week 8, week 32 and week 56 ]
  5. 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

  6. Measure of concentrations of dolutegravir(Tivicay®) and lamivudine(Epivir®) in case of virological failure or with a blip [ Time Frame: week 56 ]
  7. Measure of adherence to treatment (self-reported) [ Time Frame: Day 0, week 4, week 8, week 32 and week 56 ]
  8. Measure of quality of life (self-reported) [ Time Frame: Day 0, week 8 and week 56 ]
  9. 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.

  10. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527096


Locations
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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
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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

Additional Information:
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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 ( EudraCT Number )
First Posted: August 18, 2015    Key Record Dates
Last Update Posted: August 22, 2017
Last Verified: August 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:
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Lamivudine
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors