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MainTitle

Study to Evaluate the Efficacy of MONotherapy of TiviCAY® Versus a Triple Therapy in HIV-1-infected Patients (MONCAY)

This study is currently recruiting participants. (see Contacts and Locations)

Verified March 2017 by Centre Hospitalier Régional d'Orléans

Sponsor
Centre Hospitalier Régional d'Orléans


Information provided by (Responsible Party)
Centre Hospitalier Régional d'Orléans
ClinicalTrials.gov Identifier
NCT02596334

First received: October 16, 2015
Last updated: March 24, 2017
Last Verified: March 2017
History of Changes
Purpose

Purpose

Triple antiretroviral regimens have greatly improved the prognosis of patients living with HIV (PLHIV). Patients virologically controlled and having a good immune restoration can have a life expectancy close or equal to that of people not infected with HIV.[1] However, this is under the condition of a "lifetime" maintenance of an undetectable plasma viral load (pVL) (<50 cp/ml). On the other hand it is well established that aging increases comorbidities among PLHIV and the burden of co-medications.[2] This also has the consequence of frequent drug-drug interactions. In this context it is important to decrease pills burden, side-effects and drug-drug interactions, while maintaining undetectability.

Currently, there is a strong interest for medical research to validate lightened regimens (i.e. bithérapies [3-7] and monothérapies [8,9], particularly in a maintenance strategy, with the primary objective of reducing burden of pills and side effects. Several monotherapy trials using a boosted protease inhibitor (PI/r) showed high level of viral suppression, even if this proportion was not always non-inferior to maintaining a triple therapy. [8,9] Fortunately, when virological failure occurred under monotherapy virologic suppression was easily restored by the addition of two NRTI. Patients who are most likely to maintain viral suppression under a reduced scheme are those that have a high nadir (> 100 CD4 / mm3), no previous AIDS event and a sustained virologic suppression (>12 months).

Monotherapy is the option that best reduces the burden of pills and the risk of side effects or drug-drug interactions. It must be considered using very powerful molecule that harbor a strong binding to its ligand in order to minimize the risk of selecting resistant mutants in the case of virologic failure. To be as simple as possible in its use, it must be a single agent administered as a single dose once a day and not boosted if possible. The molecule must have very good tolerance. Finally, to be effective in viral sanctuaries this molecule should have a good (or sufficient) diffusion to ensure effective Cmin on wild viral strains. Dolutegravir meets all these exigences.[10] In addition, our team recently presented results of a pilot study showing that the switch of a successful combined antiretroviral regimen to dolutegravir monotherapy maintained undetectable viral load (<20 cp/ml) after a median of 7 months (range 6.5-10 months).

Condition Intervention Phase
HIV

Drug : dolutegravir 50mg +abacavir 600mg +lamivudine 300mg
Drug : dolutegravir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial to Evaluate the Efficacy of a Dolutegravir Monotherapy (Tivicay®) Versus the Maintenance of a Successful Triple Therapy Using Abacavir + Lamivudine + Dolutegravir (Triumeq®) in HIV-1- Infected Patients

Further study details as provided by Centre Hospitalier Régional d'Orléans:

Primary Outcome Measures

  • Viral Load [ Time Frame: Week 24 ]
    Percentage of patients having a viral load <50 copies/ml in each arm at week 24
Secondary Outcome Measures:
  • Viral load [ Time Frame: between Week 4 and Week 48 ]
    Percentage of patients having a confirmed viral load > 50 copies/ml between week 4 and week 48
  • Delta CD 4 [ Time Frame: until Week 48 ]
    delta CD4 in each arms from Baseline to W48, comparison between arms
  • Residual activation measures (sub study) [ Time Frame: Week 24 ]
    CD4+CD38+DR+, CD8+CD38+DR+
  • Residual activation marker measures (sub study) [ Time Frame: Week 24 ]
    sCD14, sCD163,
  • Pro-inflammatory cytokins measures (sub study) [ Time Frame: Week 24 ]
    TNFα, IFNγ, IL6, IP-10
  • Inflammatory marker measures (sub study) [ Time Frame: Week 24 ]
    CRPus
  • virus genotype [ Time Frame: Until Week 48 ]
    Evolution of viruses genotype profiles of patients who present a virologic failure
  • RNA viral load (sub study) [ Time Frame: Week 24 ]
    RNA viral load in the genital tract (cervico-vaginal secretions or sperm): comparison between arms
  • HIV DNA evolution [ Time Frame: between day 0 and week 48 ]
    HIV DNA evolution in each arm from baseline to W48; comparison between arms
  • Virological failure predictive factors [ Time Frame: 48 weeks ]
    Determination of virological failure predictive factors
  • Impact of the strategy on the acceptability and quality of life [ Time Frame: 48 weeks ]
    determination of quality of life with questionnary, comparison between arms
  • Proportion of patients with an adverse event [ Time Frame: 48 weeks ]
  • Proportion of patients with a severe adverse event [ Time Frame: 48 weeks ]
  • Creatinine clearance change [ Time Frame: 48 weeks ]
    Biological parameters evolution in each arm
  • Lipidic profiles [ Time Frame: 48 weeks ]
    Biological parameters evolution in each arm
  • Clinical events [ Time Frame: 48 weeks ]
    Clinical events with progression to AIDS or death. Proportion of individuals developing a new CDC-event (as defined by cdc 1993 classification) from baseline to week 48.

Estimated Enrollment: 160
Study Start Date: December 23, 2015
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: triple therapy
dolutegravir + abacavir + lamivudine (TRIUMEQ) : oral administration, one tablet daily during 48 weeks.
Drug: dolutegravir 50mg +abacavir 600mg +lamivudine 300mg
Other Name: Triumeq, EU/1/14/940/001
Experimental: monotherapy
dolutegravir (TIVICAY) : 50 mg, oral administration, one tablet daily during 48 weeks.
Drug: dolutegravir
Other Name: Tivicay , EU/1/13/892/001
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 patients with no previous AIDS event (excluding a healed tuberculosis);
  • Current antiretroviral treatment associating dolutegravir + abacavir + lamivudine for at least 1 month;
  • Nadir CD4 ≥ 100/mm3;
  • Plasma RNA viral load < 50 copies/ml for at least 12 months;
  • Plasma RNA viral load <20 or 40 copies/ml (according to the threshold of the method used by local laboratory) at the screening visit;
  • No documented virologic failure or known resistance to any integrase inhibitor,
  • Patient having provided a written consent;
  • Patients follow-up possible in ambulatory;
  • Patient age > 18 years;
  • Covered by health insurance


Exclusion Criteria:
  • Non-compliant patient
    • Subject is pregnant, or lactating, or of childbearing potential and without contraception;
    • Active opportunistic infections (defining AIDS);
    • Known hypersensibility to abacavir or lamivudine or dolutegravir;
    • Patients harboring HLA B*5701;
    • Major overweight (BMI ≥ 40);
    • Weight <40 kg;
    • Creatinine clearance < 50ml/min;
    • Cirrhosis or severe liver failure (factor V < 50%);
    • Life Prognosis threatened within 6 months;
    • Circumstances that may impair judgment or understanding of the information given to the patient;
    • Co-medication with carbamazepin, oxcarbamazepin, fosphenytoïn, phenobarbital, phenytoïn, primidon, St John's wort or dofetilid;
    • Malabsorption syndromes;
    • The following laboratory criteria:
      • Serum AST,ALT > 5 x upper limit of normal (ULN)
      • Thrombocytopenia with platelet count < 50.000/ml
      • Anemia with hemoglobin < 8g/dl
      • Polynuclear neutrophil count < 500/mm3

      contacts and locations

      Contacts and Locations

      Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

      Please refer to this study by its ClinicalTrials.gov identifier: NCT02596334

      Contacts

      Contact:   DESPUJOLS Aurélie 33 2 38 74 40 71 aurelie.despujols@chr-orleans.fr
      Contact:   THOMAS Gaëlle 33 2 38 61 34 49 gaêlle.thomas@chr-orleans.fr

      Locations

      France
      CHD de VENDEE Not yet recruiting
      La Roche sur Yon, France, 85925
      Principal Investigator: ESNAULT Jean Luc
      CH de LA ROCHELLE Recruiting
      La Rochelle, France, 17019
      Principal Investigator: RONCATO-SABERAN Mariam
      CHRU de NANTES Recruiting
      Nantes, France, 44093
      Principal Investigator: RAFFI François
      CH de NIORT Recruiting
      Niort, France, 79021
      Principal Investigator: DOS SANTOS Anabele
      CHR d'ORLEANS Recruiting
      Orleans, France, 45032
      Principal Investigator: PRAZUCK Thierry
      Sub-Investigator: HOCQUELOUX Laurent
      CHRU de POITIERS Recruiting
      Poitiers, France, 86021
      Principal Investigator: LE MOAL Gwenaël
      CHU de STRASBOURG Recruiting
      Strasbourg, France, 67000
      Principal Investigator: REY David
      CHRU de TOURS Recruiting
      Tours, France, 37044
      Principal Investigator: BERNARD Louis
      CHU de NANCY Not yet recruiting
      Vandoeuvre Les Nancy, France, 54511
      Principal Investigator: MAY Thierry

      Sponsors and Collaborators

      Centre Hospitalier Régional d'Orléans

      Investigators

      Study Director: HOCQUELOUX Laurent CHR d'ORLEANS
      More Information

      More Information


      Responsible Party: Centre Hospitalier Régional d'Orléans  
      ClinicalTrials.gov Identifier: NCT02596334   History of Changes  
      Other Study ID Numbers: CHRO 2015-03  
      Study First Received: October 16, 2015  
      Last Updated: March 24, 2017  

      Keywords provided by Centre Hospitalier Régional d'Orléans:

      HIV-1 infected patient
      monotherapy
      dolutegravir

      Additional relevant MeSH terms:
      Lamivudine
      Abacavir
      Dolutegravir

      ClinicalTrials.gov processed this data on October 23, 2017
      This information is provided by ClinicalTrials.gov.