A Phase III, randomized, multicenter, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravirplus rilpivirine from current integrase inhibitor, NNRTI, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed
- Conditions
- Human immunodeficiency virus type 1 (HIV-1)MedDRA version: 20.1Level: LLTClassification code 10003582Term: Asymptomatic human immunodeficiency virus type I infectionSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2014-005148-16-IT
- Lead Sponsor
- VIIV HEALTHCARE UK LIMITED
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 518
Eligible subjects must:
- be able to understand and comply with protocol requirements, instructions, and restrictions;
- be likely to complete the study as planned;
- be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g., no active substance abuse, acute major organ disease, or planned long-term work
assignments out of the country, etc.).
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. HIV-1 infected men or women =18 years of age;
2. Must be on uninterrupted current regimen (either the initial or second cART regimen) for at least 6 months prior to Screening Any prior switch
, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns or access to medications, or convenience/simplification.
Acceptable stable cART regimens prior to Screening include 2 NRTIs plus:
•INI (either the initial or second cART regimen)
•NNRTI (either the initial or second cART regimen)
•Boosted PI (or atazanavir [ATV] unboosted)(either the initial or second PI-based cART regimen);
3. Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to
Screening;
4. Plasma HIV-1 RNA <50 c/mL at Screening;
5. A female, may be eligible to enter and participate in the study if she:
a. is of non-child-bearing potential either defined as post-menopausal (12 months of spontaneous amenorrhea and =45 years of age) or
physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
b. is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of
contraception to avoid pregnancy:
- Complete abstinence from intercourse from 2 weeks prior to administration of study drug, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
- Male condom/spermicide, male condom/diaphragm,
diaphragm/spermicide;
- Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see the SPM for a listing describing criteria of approved IUDs);
- Male partner sterilization prior to the female subject's entry into the study and this male is the sole partner for that subject;
- Approved hormonal contraception for subjects randomly assigned to DTG + RPV arm or approved hormonal contraception plus a barrier method for subjects assigned to CAR (see the SPM for a listing of examples of approved hormonal contraception);
- Any other method with published data showing that the expected failure rate is <1% per year.
Any contraception method must be used consistently, in accordance with the approved product label during treatment with study drug and for at least 2 weeks after discontinuation of study drug.
All subjects participating in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier
methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner.
6. Subject is willing and able to understand requirements of study participation and provide signed and dated written informed consent prior to Screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18
A subject will not be eligible for inclusion in this study if any of the
following criteria apply:
Exclusionary Criteria prior to Screening or Day 1
1. Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement >=50 c/mL;
2. Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL;
3. Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, 2 or more plasma HIV-1 RNA measurements >=50 c/mL;
4. Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening, except for brief periods (less than 1
month) where all ART was stopped due to tolerability and/or safety concerns;
5. Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy
(defined as a confirmed plasma HIV-1 RNA measurement > or = 400 c/mL after initial suppression to <50 c/mL while on first line HIV
therapy regimen);
Exclusionary medical conditions
6. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study;
7. Any evidence of an active Centers for Disease Control and Prevention (CDC) Category C disease. Exceptions include cutaneous Kaposi's sarcoma not requiring systemic therapy and historic CD4+ lymphocyte counts of <200 cells/mm3;
8. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh Classification C Appendix 2 of study Protocol, p98);
13. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell
carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study Medical Monitor
for inclusion of the subject prior to randomization;
14. Subjects who in the investigator's judgment pose a significant suicidality risk. Subject's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk;
Exclusionary Treatments prior to Screening or Day 1
18. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;
19. Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any
immunomodulators that alter immune responses (a list of examples is provided in the SPM);
20. Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the
biological effect of the test agent, whichever is longer, prior to Day 1 of the study;
**Please refer to study Protocol 201637, for continuing list of the Exclusion Criteria*
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method