A Phase III, Randomized, Multicenter, Open-label, Non-inferiority Study Evaluating the Efficacy, Safety and Tolerability of Switching to Dolutegravir/Lamivudine Fixed Dose Combination in HIV-1 Infected Adults Who Are Virologically Suppressed

ViiV Healthcare1 site in 1 country493 target enrollmentNovember 11, 2019

ConditionsHIV Infections

InterventionsDTG/3TC FDC CAR

DrugsDTG/3TC FDC CAR

Overview

Phase: Phase 3
Intervention: DTG/3TC FDC
Conditions: HIV Infections
Sponsor: ViiV Healthcare
Enrollment: 493
Locations: 1
Primary Endpoint: Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) >=50 Copies/Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Category at Week 48
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The aim of this study is to determine if virologically suppressed Human Immunodeficiency Virus (HIV) Type 1 infected adults on a current antiretroviral regimen (CAR) (including 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a third agent) remain suppressed upon switching to dolutegravir/lamivudine (DTG/3TC) fixed dose combination (FDC). The main objective of the study is to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks in virologically suppressed adults living with HIV-1. The study will also evaluate information regarding the safety and health related quality of life. The study will include Screening Phase (up to 28 days), a Randomization Phase (up to Week 52) and a Continuation Phase (post Week 52). The Continuation Phase is not applicable for participants in Sweden and Denmark. Approximately 490 participants will be randomized in 1:1 ratio to receive DTG/3TC FDC once daily for up to 52 weeks or continue their CAR for 52 weeks. Participants in the DTG/3TC FDC arm who successfully complete up to 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in Continuation Phase.

Registry

clinicaltrials.gov

Start Date

November 11, 2019

End Date

September 9, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

ViiV Healthcare

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Eligible participants must be able to understand and comply with protocol requirements, instructions, and restrictions; participant must be likely to complete the study as planned; participants should be considered appropriate candidates for participation in an investigative clinical trial with oral medication (example given \[e.g.\] no active problematic substance abuse, acute major organ disease, or potential long-term work assignments out of the country).
•Participant should be aged 18 years or older (or older, if required by local regulatory agencies), at the time of signing the informed consent.
•Participants living with HIV.
•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.
•Plasma HIV-1 RNA \<50 c/mL at Screening.
•Participant must be on uninterrupted current regimen (either the initial or second Combination antiretroviral therapy \[cART\] regimen) for at least 3 months prior to Screening.
•i) 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 and must not have been done for suspected or established treatment failure. The following switches, if they are the only switches, would not be considered a change in regimen. a) A switch from a PI boosted with ritonavir (RTV) to the same PI boosted with cobicistat is allowed (and vice versa). b) A switch from 3TC to emtricitabine (FTC) (and vice versa). c) A switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) (and vice versa).
•ii) Acceptable stable cART regimens prior to Screening include 2 NRTIs plus a) INI (either the initial or second cART regimen) b) NNRTI (either the initial or second cART regimen) c) Boosted PI (or atazanavir \[ATV\] unboosted) (either the initial or second PI-based cART regimen).
•A male or female participant.
•A female participant is eligible to participate if she is not pregnant \[as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at randomization (a local serum hCG test at randomization is allowed if it can be done, and results obtained, within 24 hours prior to randomization)\], not breastfeeding, and at least one of the following conditions applies; not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period from 28 days prior to the first dose of study medication and for at least 2 weeks after the last dose of study medication. All participants 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; The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

Exclusion Criteria

•Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
•Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease except cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells per cubic millimeter (mm\^3) are not exclusionary.
•Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
•Participants with unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
•Participants with the evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Participant's positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. Anti-HBc must be either total anti-HBc or anti-HBc immunoglobulin G (IgG), and not anti-HBc Immunoglobulin M (IgM). Participants with a documented history of chronic HBV and current undetectable HBV DNA while on a TAF/TDF regimen are excluded.
•Participants with anticipated need for any hepatitis C virus (HCV) therapy during the randomized phase of the study, or anticipated need for HCV therapy with a potential for adverse drug-drug interactions with DTG or 3TC.
•Participants with untreated syphilis infection (positive rapid plasma reagin \[RPR\] at Screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible.
•Participants with history or presence of allergy intolerance to the study interventions or their components or drugs of their class.
•Participants with ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.
•Participants who in the investigator's judgment, poses a significant suicidality risk.

Arms & Interventions

Participants receiving DTG/3TC FDC

Eligible participants will be randomized to receive 50 milligrams (mg)/300 mg DTG/3TC FDC therapy from Day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.

Intervention: DTG/3TC FDC

Participants receiving CAR

Eligible participants will continue to receive CAR from Day 1 up to 52 weeks.

Intervention: CAR

Outcomes

Primary Outcomes

Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) >=50 Copies/Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Category at Week 48

Time Frame: Week 48

Number of participants with plasma HIV 1 RNA \>=50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA \>=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

Secondary Outcomes

Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 48(Week 48)
Number of Participants With Plasma HIV-1 RNA >=50 c/mL as Per FDA Snapshot Category at Week 24(Week 24)
Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 24(Week 24)
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Week 24(Baseline (Day 1) and Week 24)
Change From Baseline in CD4+ Cell Count for Week 48(Baseline (Day 1) and Week 48)
Change From Baseline in CD4+/ Cluster of Differentiation 8 (CD8+) Cell Counts Ratio for Week 24(Baseline (Day 1) and Week 24)
Change From Baseline in CD4+/CD8+ Cell Counts Ratio for Week 48(Baseline (Day 1) and Week 48)
Number of Participants With Disease Progression Through Week 24(Up to Week 24)
Number of Participants With Disease Progression Through Week 48(Up to Week 48)
Number of Participants With Adverse Events (AEs) and AEs Leading to Discontinuation(Up to Week 52)
Number of Participants With AEs by Severity Grades(Up to 52 weeks)
Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks(Up to Week 52)
Number of Participants With Any AEs and AEs by Severity Grades for Those Participants With Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2(Up to 52 weeks)
Number of Participants With Any AEs and AEs by Severity Grades for Those Participants With Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2(Up to 52 weeks)
Number of Participants With Any AEs Leading to Discontinuation Based on Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2(Up to 52 weeks)
Number of Participants With Any AEs Leading to Discontinuation Based on Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2(Up to 52 weeks)
Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks Based on Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2(Up to Week 52)
Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks Based on Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2(Up to Week 52)
Change From Baseline in Fasting Lipids at Week 24(Baseline (Day 1) and Week 24)
Change From Baseline in Fasting Lipids at Week 48(Baseline (Day 1) and Week 48)
Number of Participants With Observed Genotypic and Phenotypic Resistance to Antiretrovirals (ARVs) for Participants Meeting Confirmed Virologic Withdrawal (CVW) Criteria(Up to week 48)
Change From Baseline in Health Status by HIV Treatment Satisfaction Questionnaire (TSQ) at Week 24(Baseline (Day 1) and Week 24)
Change From Baseline in Health Status by HIV TSQ at Week 48(Baseline (Day 1) and Week 48)
Change From Baseline in Health Status by Symptom Distress Module (SDM) at Week 24(Baseline (Day 1) and Week 24)
Change From Baseline in Health Status by SDM at Week 48(Baseline (Day 1) and Week 48)
Change From Baseline in Health Status by SDM in Continuation Phase(Baseline (Day 1) and Week 76, Week 100, and Week 132)