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)

NCT02527096 | Completed Phase 2

• 2 other identifiers: ANRS 167 Lamidol2015-001492-44
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 18

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.

Conditions

HIV-1 Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Virological success without any intercurrent event leading to interrupt the strategy of the trial (analysis)

  Virological failure is defined by plasma HIV RNA \> 50 cp/mL on 2 following samples at 2 to 4 weeks apart.

  from week 8 to week 56 (± 4 weeks)

Secondary Outcomes (10)

• Evolution of CD4 and CD8 lymphocytes count (analysis)

  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)

  week 56

• Profile of resistance mutations in plasma in case of virological failure

  week 56

• Percentage of participants with plasma HIV RNA < 1 cp/mL

  Day 0, week 8, week 32 and week 56

• Influence of total DNA on the occurrence of virological failure or blip

  from Day 0 to week 56

Study Arms (1)

dolutegravir(Tivicay®) and lamivudine(Epivir®)

EXPERIMENTAL

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

Interventions

dolutegravir (Tivicay®) - Phase 1 DRUG

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

dolutegravir(Tivicay®) and lamivudine(Epivir®)

lamivudine (Epivir®) - Phase 2 DRUG

• 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®) and lamivudine(Epivir®)

dolutegravir (Tivicay®) - Phase 2 DRUG

• 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®) and lamivudine(Epivir®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• HIV-2 infection
• Positive HBc Ac isolated
• 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 under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties) or under legal guardianship.

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• ViiV Healthcare: collaborator

Study Sites (18)

Hôpital Avicenne

Bobigny, 93009, France

Location

Hôpital Saint-André

Bordeaux, 33000, France

Location

Hôpital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

Hôpital du Bocage

Dijon, 21079, France

Location

Hôpital Pierre Zobda-Quitman

Fort de France, 97261, France

Location

Hôpial Bicêtre

Le Kremelin Bicêtre, 94270, France

Location

Hôpital Gui de Chaudiac

Montpellier, 34295, France

Location

Hôpital de l'Hotel Dieu

Nantes, 44093, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

Hôpital Saint-Antoine

Paris, 75012, France

Location

Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location

Hôpital Necker

Paris, 75015, France

Location

Hôpital Bichat

Paris, 75018, France

Location

Centre hospitalier de Pernignan

Perpignan, 66046, France

Location

Hôpital Pontchaillou

Rennes, 35033, France

Location

Hôpital Purpan

Toulouse, 31059, France

Location

Hôpital Gustave Dron

Tourcoing, 59208, France

Location

Hôpital Bretonneau

Tours, 37044, France

Location

Related Links

• Related Info

MeSH Terms

Interventions

dolutegravir; Clinical Trials, Phase I as Topic; Lamivudine; Clinical Trials, Phase II as Topic

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Véronique JOLY, MD

  Service des Maladies Infectieuses, Hôpital Bichat-Claude Bernard, Paris

  PRINCIPAL INVESTIGATOR

• Yazdan YAZDANPANAH, MD

  Service des Maladies Infectieuses, Hôpital Bichat-Claude Bernard

  STUDY CHAIR

• Roland LANDMAN, MD

  Institut de Médecine et Epidémiologie Appliquée (IMEA), Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 18, 2015
• Study Start: September 17, 2015
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

FR (18)