A Phase III, randomized, multicenter, parallel-group, noninferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current INI-, 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: 17.1Level: LLTClassification code 10003582Term: Asymptomatic human immunodeficiency virus type I infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2014-005148-16-ES
• Lead Sponsor: ViiV Healthcare, S.L.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04-14
• Last Update Posted: 24 August 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 476

Inclusion Criteria

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
to a second cART regimen, 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) (must be initial cART
regimen; one within class switch permitted for tolerability);
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 IP, 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 IP 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.
7. For subjects enrolled in France: a subject will be

Exclusion Criteria

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);
9. Unstable liver disease (as defined by the presence of any of the
following: ascites, encephalopathy, coagulopathy, hypoalbuminaemia,
oesophageal or gastric varices, or persistent jaundice), cirrhosis, known
biliary abnormalities (with the exception of Gilbert's syndrome or
asymptomatic gallstones);
10. Evidence of Hepatitis B virus (HBV) infection based on the results of
testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core
antibody (anti-HBc), and antibodies against Hepatitis B surface antigen
(anti-HBsAg) as follows:
- Subjects positive for HBsAg are excluded;
- Subjects positive for anti-HBc (negative HBsAg status) and negative for
anti-HBsAg are excluded.
11. Subjects with an anticipated need for any Hepatitis C virus (HCV)
therapy during the Early Switch Phase and for interferon-based therapy
for HCV throughout the entire study period;
A subject will not be eligible for inclusion in this study if any of the
following criteria apply:
12. History or presence of allergy to the study drugs or their components
or drugs of their class;
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
Studymedical 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;
15. Any pre-existing physical or mental condition (including substance
abuse disorder) which, in the opinion of the Investigator, may interfere
with the subject's ability to comply with the dosing schedule and/or
protocol evaluations or which may compromise the safety of the subject;
16. Any c

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified