Human immunodeficiency virus type 1 (HIV-1) MedDRA version: 17.1 Level: LLT Classification code 10003582 Term: Asymptomatic human immunodeficiency virus type I infection System Organ Class: 100000004862
Conditions
Sponsors
ViiV Healthcare, S.L.
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 200 c/mL; 3. Within the 6 to 12 month window prior to Screening and after confirmed suppression to 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the non-inferior antiviral activity of switching to dolutegravir (DTG) plus rilpivirine (RPV) once daily compared to continuation of current antiretroviral regimen (CAR) over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced subjects.;Secondary Objective: - To evaluate the immunological activity of DTG + RPV once daily compared to continuation of CAR. - To evaluate the antiviral activity of DTG + RPV once daily compared to continuation of CAR. - To evaluate the safety and tolerability of DTG + RPV once daily compared to continuation of CAR over time. - To evaluate renal (in urine and blood), bone (in blood), and cardiovascular biomarkers (in blood) in subjects treated with DTG + RPV compared to continuation of CAR. - To evaluate the effects of DTG + RPV once daily on fasting lipids over time compared to continuation of CAR. - To assess viral resistance in subjects meeting Virologic Withdrawal Criteria. - To evaluate DTG and RPV trough concentrations. - To evaluate the DTG and RPV trough concentrations over time during the initial post-switch period in the first 20 subjects in the NNRTI Subset who switch from EFV or NVP to DTG + RPV. REFER TO PROTOCOL (page 18, section3) FOR COMPLETE LIST SECONDARY OBJECTIVES.;Primary end point(s): Proportion of subjects with plasma HIV-1 RNA <50 copies per milliliter (c/mL) at Week 48 using the Snapshot algorithm for the Intent-to-treat exposed (ITT-E) population.;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from Baseline in CD4+ lymphocyte count at Weeks 24 and 48; Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 24, using the Snapshot algorithm for the ITT-E Population; Incidence and severity of adverse events (AEs) and laboratory abnormalities over 48 weeks; Proportion of subjects who discontinue treatment due to AEs over 48 weeks; Change from Baseline in renal, bone, and cardiovascular biomarkers at Week 48; Change from Baseline in fasting lipids at Weeks 24 and 48; Incidence of observed genotypic and resistance to CAR and to DTG or RPV for subjects meeting Virologic Withdrawal Criteria; Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76, 100, or Withdrawal in subjects switching to DTG + RPV Pre-dose concentrations of DTG and RPV at Weeks 2, 4 and 8 in the first 20 subjects in the NNRTI Subset who switch from EFV or NVP to DTG +RPV By Baseline third agent treatment class: Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 using the Snapshot algorithm for the ITT-E Population; Changes from Baseline in CD4+ lymphocyte counts at Week 48; Incidence and severity of AEs and laboratory abnormalities over 48 weeks; Proportion of subjects who discontinue treatment due to AEs over 48 weeks; Incidence of observed genotypic and phenotypic resistance to current antiretroviral regimen and to DTG or RPV for subjects meeting Virologic Withdrawal Criteria; Change from Baseline in fasting lipids at Weeks 24 and 48; Between and within treatment group comparisons will be assessed on change from Baseline in pre-specified treatment symptoms (using the HIV Symptom Index) at Weeks 4, 24, 48, 56, 76, 100 and 148 (or Withdrawal from the study); Between and within treatment group comparisons will be assessed on change from Baseline treatment satisfaction (using the HIV TSQ) at Weeks 4, 24, 48, 56, 76, 100 and 148 (or Withdrawal from the study);Timepoint(s) of evaluation of this end point: Please see field E.5.2 above for | — |
Countries
Argentina, Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactCentro de Información
GlaxoSmithKline
Outcome results
None listed