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)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by Nantes University Hospital
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT02067767
First received: February 18, 2014
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: Abacavir/Lamivudine/Dolutegravir
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • Percentage of patients with plasma HIV-1 RNA < 50 copies/mL at week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Percentage of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W36 [ Time Frame: Week 36 ] [ Designated as safety issue: No ]
  • Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Percentage of patients with adverse event of any Grade over 12 weeks [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
  • Percentage of patients with adverse event of Grade 3 or 4 over 48 weeks [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  • CD4 and CD8 measurement [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Changes in CD4 and CD8 counts over 48 weeks

  • Serum creatinine and GFR (MDRD) measurement [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Changes in serum creatinine, and GFR (MDRD) from W2 to W48

  • Urinary albumine:creatinine ratio measurement [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Change in urinary albumine:creatinine ratio over 48 weeks

  • Fasting lipids measurement [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Changes in fasting lipids over 48 weeks

  • Plasma concentration of NVP between Week 0 (W0) and Week 2 (W2) [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    The mean plasma concentration of nevirapine is measured between W0 and W2 (D0, W1, W2)

  • Plasma concentration of dolutegravir between W0 and W12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The mean plasma concentration of dolutegravir is measured between W0 and W12 (W1, W2, W4, W12)

  • CD14 and usCRP measurement over 48 weeks [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Changes in sCD14 and usCRP over 48 weeks (stored plasma)

  • Evaluation of patient's satisfaction with HIVTSQs and HIVTSQc questionnaires [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Patient's satisfaction, evaluated with self-administered questionnaires HIVTSQs and HIVTSQc

  • Plasma concentration of DTG on 24h at D0 and Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    24h PK parameters of DTG (D0, after 5 days of combination of ABC/3TC + NVP + DTG) with and without NVP (D14)


Estimated Enrollment: 53
Study Start Date: February 2014
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abacavir/Lamivudine/Dolutegravir
Patients switched from their ongoing treatment of ABC/3TC + NVP to ABC/3TC/DTG.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02067767

Contacts
Contact: François RAFFI, Pr 02 40 08 31 10 francois.raffi@chu-nantes.fr
Contact: Clotilde ALLAVENA, Dr 02 40 08 31 10 clotilde.allavena@chu-nantes.fr

Locations
France
La Roche-sur-Yon Hospital Not yet recruiting
La Roche-sur-Yon, France
Contact: Philippe PERRE, Dr    02 51 44 61 61      
Principal Investigator: Philippe PERRE, Dr         
Nantes University Hospital Not yet recruiting
Nantes, France
Contact: Clotilde ALLAVENA, Dr    02 40 08 31 10      
Principal Investigator: Clotilde ALLAVENA, Dr         
Sponsors and Collaborators
Nantes University Hospital
Investigators
Study Chair: François RAFFI, Pr Nantes University Hospital
  More Information

No publications provided

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02067767     History of Changes
Other Study ID Numbers: RC13_0230
Study First Received: February 18, 2014
Last Updated: February 19, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Nantes University Hospital:
HIV-1 infection
Nevirapine
Dolutegravir
Anti-retroviral agents

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Nevirapine
Lamivudine
Abacavir
Dolutegravir
Anti-Retroviral Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors

ClinicalTrials.gov processed this record on September 11, 2014