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

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ClinicalTrials.gov Identifier: NCT02596334
Recruitment Status : Terminated (5 patients on tivicay had virological failure)
First Posted : November 4, 2015
Last Update Posted : November 12, 2018
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Régional d'Orléans

Tracking Information
First Submitted Date  ICMJE October 16, 2015
First Posted Date  ICMJE November 4, 2015
Last Update Posted Date November 12, 2018
Actual Study Start Date  ICMJE December 23, 2015
Actual Primary Completion Date June 23, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 2, 2015)
Viral Load [ Time Frame: Week 24 ]
Percentage of patients having a viral load <50 copies/ml in each arm at week 24
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02596334 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2018)
  • 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 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2015)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Efficacy of MONotherapy of TiviCAY® Versus a Triple Therapy in HIV-1-infected Patients
Official Title  ICMJE 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
Brief Summary

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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE
  • Drug: dolutegravir 50mg +abacavir 600mg +lamivudine 300mg
    Other Name: Triumeq, EU/1/14/940/001
  • Drug: dolutegravir
    Other Name: Tivicay , EU/1/13/892/001
Study Arms  ICMJE
  • Active Comparator: triple therapy
    dolutegravir + abacavir + lamivudine (TRIUMEQ) : oral administration, one tablet daily during 48 weeks.
    Intervention: Drug: dolutegravir 50mg +abacavir 600mg +lamivudine 300mg
  • Experimental: monotherapy
    dolutegravir (TIVICAY) : 50 mg, oral administration, one tablet daily during 48 weeks.
    Intervention: Drug: dolutegravir
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 21, 2018)
158
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2015)
160
Actual Study Completion Date  ICMJE June 23, 2018
Actual Primary Completion Date June 23, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02596334
Other Study ID Numbers  ICMJE CHRO 2015-03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Centre Hospitalier Régional d'Orléans
Study Sponsor  ICMJE Centre Hospitalier Régional d'Orléans
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: HOCQUELOUX Laurent CHR d'ORLEANS
PRS Account Centre Hospitalier Régional d'Orléans
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP