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

NCT ID: NCT02596334

Last Updated: 2018-11-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-23
• Study Completion Date: 2018-06-23

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).

Conditions

HIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

triple therapy

dolutegravir + abacavir + lamivudine (TRIUMEQ) : oral administration, one tablet daily during 48 weeks.

Group Type: ACTIVE_COMPARATOR

dolutegravir 50mg +abacavir 600mg +lamivudine 300mg

Intervention Type: DRUG

monotherapy

dolutegravir (TIVICAY) : 50 mg, oral administration, one tablet daily during 48 weeks.

Group Type: EXPERIMENTAL

dolutegravir

Intervention Type: DRUG

Interventions

dolutegravir 50mg +abacavir 600mg +lamivudine 300mg

Intervention Type: DRUG

dolutegravir

Intervention Type: DRUG

Other Intervention Names

Triumeq, EU/1/14/940/001; Tivicay , EU/1/13/892/001

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Régional d'Orléans

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

HOCQUELOUX Laurent

Role: STUDY_DIRECTOR

CHR d'ORLEANS

Locations

CHD de VENDEE

La Roche-sur-Yon, , France

CH de LA ROCHELLE

La Rochelle, , France

CHRU de NANTES

Nantes, , France

CH de NIORT

Niort, , France

CHR d'ORLEANS

Orléans, , France

CHRU de POITIERS

Poitiers, , France

CHU de STRASBOURG

Strasbourg, , France

CHRU de TOURS

Tours, , France

CHU de NANCY

Vandœuvre-lès-Nancy, , France

Countries

France

References

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Other Identifiers

CHRO 2015-03

Identifier Type: -

Identifier Source: org_study_id