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) (SWAD)

February 19, 2016 updated by: Nantes University Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
53

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • La Roche-sur-Yon, France
        • La Roche-sur-Yon Hospital
      • Nantes, France
        • Nantes University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of patients with plasma HIV-1 RNA < 50 copies/mL at week 12
Time Frame: Week 12
Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W24
Time Frame: Week 24
Week 24
Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W48
Time Frame: Week 48
Week 48
Percentage of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W12
Time Frame: Week 12
Week 12
Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W24
Time Frame: Week 24
Week 24
Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W36
Time Frame: Week 36
Week 36
Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W48
Time Frame: Week 48
Week 48
Percentage of patients with adverse event of any Grade over 12 weeks
Time Frame: Week 12
Week 12
Percentage of patients with adverse event of Grade 3 or 4 over 48 weeks
Time Frame: Week 48
Week 48
CD4 and CD8 measurement
Time Frame: Week 48
Changes in CD4 and CD8 counts over 48 weeks
Week 48
Serum creatinine and GFR (MDRD) measurement
Time Frame: Week 48
Changes in serum creatinine, and GFR (MDRD) from W2 to W48
Week 48
Urinary albumine:creatinine ratio measurement
Time Frame: Week 48
Change in urinary albumine:creatinine ratio over 48 weeks
Week 48
Fasting lipids measurement
Time Frame: Week 48
Changes in fasting lipids over 48 weeks
Week 48
Plasma concentration of NVP between Week 0 (W0) and Week 2 (W2)
Time Frame: Week 2
The mean plasma concentration of nevirapine is measured between W0 and W2 (D0, W1, W2)
Week 2
Plasma concentration of dolutegravir between W0 and W12
Time Frame: Week 12
The mean plasma concentration of dolutegravir is measured between W0 and W12 (W1, W2, W4, W12)
Week 12
CD14 and usCRP measurement over 48 weeks
Time Frame: Week 48
Changes in sCD14 and usCRP over 48 weeks (stored plasma)
Week 48
Evaluation of patient's satisfaction with HIVTSQs and HIVTSQc questionnaires
Time Frame: Week 48
Patient's satisfaction, evaluated with self-administered questionnaires HIVTSQs and HIVTSQc
Week 48
Plasma concentration of DTG on 24h at D0 and Week 2
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nantes University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: François RAFFI, Pr, Nantes University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 18, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 20, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 22, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RC13_0230

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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