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

November 8, 2018 updated by: Centre Hospitalier Régional d'Orléans

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

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

158

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • La Roche sur Yon, France, 85925
        • CHD de Vendée
      • La Rochelle, France, 17019
        • CH de la Rochelle
      • Nantes, France, 44093
        • CHRU de Nantes
      • Niort, France, 79021
        • CH de Niort
      • Orleans, France, 45032
        • CHR d'Orléans
      • Poitiers, France, 86021
        • CHRU de Poitiers
      • Strasbourg, France, 67000
        • CHU de Strasbourg
      • Tours, France, 37044
        • Chru De Tours
      • Vandoeuvre Les Nancy, France, 54511
        • CHU de Nancy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: triple therapy
dolutegravir + abacavir + lamivudine (TRIUMEQ) : oral administration, one tablet daily during 48 weeks.
Drug: dolutegravir 50mg +abacavir 600mg +lamivudine 300mg
Other Names:
  • Triumeq, EU/1/14/940/001
Experimental: monotherapy
dolutegravir (TIVICAY) : 50 mg, oral administration, one tablet daily during 48 weeks.
Drug: dolutegravir
Other Names:
  • Tivicay , EU/1/13/892/001

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Viral Load
Time Frame: Week 24
Percentage of patients having a viral load <50 copies/ml in each arm at week 24
Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
until Week 48
Residual activation measures (sub study)
Time Frame: Week 24
CD4+CD38+DR+, CD8+CD38+DR+
Week 24
Residual activation marker measures (sub study)
Time Frame: Week 24
sCD14, sCD163,
Week 24
Pro-inflammatory cytokins measures (sub study)
Time Frame: Week 24
TNFα, IFNγ, IL6, IP-10
Week 24
Inflammatory marker measures (sub study)
Time Frame: Week 24
CRPus
Week 24
virus genotype
Time Frame: Until Week 48
Evolution of viruses genotype profiles of patients who present a virologic failure
Until Week 48
RNA and DNA viral load (sub study)
Time Frame: Week 24 to week 48
RNA and DNA viral load in the genital tract (cervico-vaginal secretions or sperm): comparison between arms
Week 24 to week 48
HIV DNA evolution
Time Frame: between day 0 and week 48
HIV DNA evolution in each arm from baseline to W48; comparison between arms
between day 0 and week 48
Virological failure predictive factors
Time Frame: 48 weeks
Determination of virological failure predictive factors
48 weeks
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
48 weeks
Proportion of patients with an adverse event
Time Frame: 48 weeks
48 weeks
Proportion of patients with a severe adverse event
Time Frame: 48 weeks
48 weeks
Creatinine clearance change
Time Frame: 48 weeks
Biological parameters evolution in each arm
48 weeks
Lipidic profiles
Time Frame: 48 weeks
Biological parameters evolution in each arm
48 weeks
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.
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Régional d'Orléans

Investigators

  • Study Director: HOCQUELOUX Laurent, CHR d'Orléans

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 23, 2015

Primary Completion (Actual)

June 23, 2017

Study Completion (Actual)

June 23, 2018

Study Registration Dates

First Submitted

October 16, 2015

First Submitted That Met QC Criteria

November 2, 2015

First Posted (Estimate)

November 4, 2015

Study Record Updates

Last Update Posted (Actual)

November 13, 2018

Last Update Submitted That Met QC Criteria

November 8, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHRO 2015-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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