Multicentric Open-label Study of Switch From Abacavir/Lamivudine Fixed Dose Combination Plus Nevirapine to Abacavir/Lamivudine/Dolutegravir in Virologically Suppressed HIV-1 Infected Adults (SWAD)

HIV-1 Infection Clinical Trial

— SWAD  

Official title:

Phase 2 Multicentric Open-label Study of Switch From Abacavir/Lamivudine Fixed Dose Combination Plus Nevirapine to Abacavir/Lamivudine/Dolutegravir in Virologically Suppressed HIV-1 Infected Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02067767
• Other study ID #: RC13_0230
• Status: Completed
• Phase: Phase 2
• First received: February 18, 2014
• Last updated: February 19, 2016
• Start date: February 2014
• Est. completion date: December 2015

Study information

• Verified date: February 2015
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

Abacavir/Lamivudine + Nevirapine (ABC/3TC + NVP) is a very effective and well tolerable regimen on the long-term. However this regimen comprises 2 pills per day. Abacavir/Lamivudine/Dolutegravir (ABC/3TC/DTG) offers simplification with a single pill per day with no food constraints, Dolutegravir (DTG) having the advantage over Nevirapine (NVP) of high potency, higher genetic barrier to resistance, with a very good safety profile. The objective of this study is to evaluate the virologic safety (maintenance of virologic suppression) after switching from ABC/3TC + NVP to ABC/3TC/DTG in 50 HIV-1 infected adults with prolonged HIV RNA suppression on ABC/3TC + NVP, as well as clinical and laboratory safety. Because nevirapine is a strong inducer of hepatic enzymes, pharmacocinetic (PK) assessment will be performed in all patients in the first weeks after switch and 24-hours PK in a subset of 10 patients after 5 days of DTG addition to current regimen, before switching to ABC/3TC/DTG.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with confirmed HIV-1 infection (HIV antibody positive confirmation prior to screening)

• Age = 18 years

• Written informed consent

• Male patient or non-pregnant, non-lactating female patient

• On antiretroviral treatment with nevirapine (400 mg per day) plus abacavir/lamivudine for more than 6 months; Nevirapine 400 mg/day being administered as either 1 x 200 mg IR x 2/day or 2 x 200 mg IR qd or 1 x 400 mg XR qd

• No history of prior virologic failure on antiretroviral therapy

• HIV-1 RNA < 50 copies/ml for more than 1 year,

• No major IAS-USA nucleoside reverse transcriptase inhibitors or integrase inhibitors resistance mutations on genotypic testing on last plasma sample with HIV-1 RNA > 500 c/mL (if available)

• HLA-B*5701 negative test

• Subjects covered by Health Insurance

Exclusion Criteria:

• Woman of child-bearing potential without effective contraception method. Pregnant or breastfeeding woman.

• Woman expecting to conceive during the study period

• HIV-2 co-infection

• Any prior exposure to integrase inhibitor(s)

• Plasma HIV-1 RNA > 50 c/mL in the past year

• Creatinine clearance < 60 ml/mn (estimated glomerular filtration rate according to the MDRD equation),

• Alkaline phosphatase, ASAT or ALAT = 5 times the upper limit of the norm (ULN)

• Patient with history of decompensated liver disease

• Any major IAS-USA mutation conferring resistance to one or more of reverse transcriptase or integrase inhibitors on any historical plasma genotype if available. Any previous genotype result is valid, with no time limit, as long as the original test result is documented.

• Mycobacteriosis under treatment

• Malignancy requiring chemotherapy or radiotherapy

• Positive HBs Ag

• HCV infection for which specific treatment is ongoing or planned during the study

• Known hypersensitivity to one of the trial drugs, the metabolites or formulation excipients

• Concomitant therapy with antacids or H2 antagonists

• Contraindicated concomitant treatment

• Anticipated non-compliance with the protocol

• Participation in another clinical trial with an on-going exclusion period at screening

• Subject under legal guardianship or incapacitation

• Subject, who in the opinion of the investigator, is unable to complete the study period

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Abacavir/Lamivudine/Dolutegravir
At Day 1 (D1): group 1 will switch their ongoing treatment of ABC/3TC + NVP to ABC/3TC/DTG ; group 2 will continue NVP and switch ABC/3TC to ABC/3TC/DTG for 6 days (D-5 to D0), then stop NVP from D1.

Locations

Country	Name	City	State
France	La Roche-sur-Yon Hospital	La Roche-sur-Yon
France	Nantes University Hospital	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with plasma HIV-1 RNA < 50 copies/mL at week 12		Week 12	No
Secondary	Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W24		Week 24	No
Secondary	Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W48		Week 48	No
Secondary	Percentage of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W12		Week 12	No
Secondary	Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W24		Week 24	No
Secondary	Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W36		Week 36	No
Secondary	Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W48		Week 48	No
Secondary	Percentage of patients with adverse event of any Grade over 12 weeks		Week 12	Yes
Secondary	Percentage of patients with adverse event of Grade 3 or 4 over 48 weeks		Week 48	Yes
Secondary	CD4 and CD8 measurement	Changes in CD4 and CD8 counts over 48 weeks	Week 48	No
Secondary	Serum creatinine and GFR (MDRD) measurement	Changes in serum creatinine, and GFR (MDRD) from W2 to W48	Week 48	No
Secondary	Urinary albumine:creatinine ratio measurement	Change in urinary albumine:creatinine ratio over 48 weeks	Week 48	No
Secondary	Fasting lipids measurement	Changes in fasting lipids over 48 weeks	Week 48	No
Secondary	Plasma concentration of NVP between Week 0 (W0) and Week 2 (W2)	The mean plasma concentration of nevirapine is measured between W0 and W2 (D0, W1, W2)	Week 2	No
Secondary	Plasma concentration of dolutegravir between W0 and W12	The mean plasma concentration of dolutegravir is measured between W0 and W12 (W1, W2, W4, W12)	Week 12	No
Secondary	CD14 and usCRP measurement over 48 weeks	Changes in sCD14 and usCRP over 48 weeks (stored plasma)	Week 48	No
Secondary	Evaluation of patient's satisfaction with HIVTSQs and HIVTSQc questionnaires	Patient's satisfaction, evaluated with self-administered questionnaires HIVTSQs and HIVTSQc	Week 48	No
Secondary	Plasma concentration of DTG on 24h at D0 and Week 2	24h PK parameters of DTG (D0, after 5 days of combination of ABC/3TC + NVP + DTG) with and without NVP (D14)	Week 2	No