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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

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).


Condition or disease Intervention/treatment Phase
HIV Drug: dolutegravir 50mg +abacavir 600mg +lamivudine 300mg Drug: dolutegravir Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 158 participants
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
Actual Study Start Date : December 23, 2015
Actual Primary Completion Date : June 23, 2017
Actual Study Completion Date : June 23, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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 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




Primary Outcome Measures :
  1. 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 :
  1. 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

  2. Delta CD 4 [ Time Frame: until Week 48 ]
    delta CD4 in each arms from Baseline to W48, comparison between arms

  3. Residual activation measures (sub study) [ Time Frame: Week 24 ]
    CD4+CD38+DR+, CD8+CD38+DR+

  4. Residual activation marker measures (sub study) [ Time Frame: Week 24 ]
    sCD14, sCD163,

  5. Pro-inflammatory cytokins measures (sub study) [ Time Frame: Week 24 ]
    TNFα, IFNγ, IL6, IP-10

  6. Inflammatory marker measures (sub study) [ Time Frame: Week 24 ]
    CRPus

  7. virus genotype [ Time Frame: Until Week 48 ]
    Evolution of viruses genotype profiles of patients who present a virologic failure

  8. 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

  9. HIV DNA evolution [ Time Frame: between day 0 and week 48 ]
    HIV DNA evolution in each arm from baseline to W48; comparison between arms

  10. Virological failure predictive factors [ Time Frame: 48 weeks ]
    Determination of virological failure predictive factors

  11. 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

  12. Proportion of patients with an adverse event [ Time Frame: 48 weeks ]
  13. Proportion of patients with a severe adverse event [ Time Frame: 48 weeks ]
  14. Creatinine clearance change [ Time Frame: 48 weeks ]
    Biological parameters evolution in each arm

  15. Lipidic profiles [ Time Frame: 48 weeks ]
    Biological parameters evolution in each arm

  16. 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.



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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 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

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): NCT02596334


Locations
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France
CHD de VENDEE
La Roche sur Yon, France, 85925
CH de LA ROCHELLE
La Rochelle, France, 17019
CHRU de NANTES
Nantes, France, 44093
CH de NIORT
Niort, France, 79021
CHR d'ORLEANS
Orleans, France, 45032
CHRU de POITIERS
Poitiers, France, 86021
CHU de STRASBOURG
Strasbourg, France, 67000
CHRU de TOURS
Tours, France, 37044
CHU de NANCY
Vandoeuvre Les Nancy, France, 54511
Sponsors and Collaborators
Centre Hospitalier Régional d'Orléans
Investigators
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Study Director: HOCQUELOUX Laurent CHR d'ORLEANS

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Centre Hospitalier Régional d'Orléans
ClinicalTrials.gov Identifier: NCT02596334     History of Changes
Other Study ID Numbers: CHRO 2015-03
First Posted: November 4, 2015    Key Record Dates
Last Update Posted: November 12, 2018
Last Verified: November 2018
Keywords provided by Centre Hospitalier Régional d'Orléans:
HIV-1 infected patient
monotherapy
dolutegravir
Additional relevant MeSH terms:
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Lamivudine
Abacavir
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