An Open-label, Single Arm Study to Evaluate the Week 48 Efficacy and Safety of a Two-drug Regimen of Dolutegravir/Lamivudine (DTG/3TC) as a Fixed Dose Combination (FDC), in Antiretroviral Therapy (ART)-Naive HIV-1-infected Adolescents, ≥12 to <18 Years of Age Who Weigh at Least 25 kg

ViiV Healthcare1 site in 1 country32 target enrollmentMay 6, 2019

ConditionsHIV Infections

InterventionsDTG + 3TC FDC

DrugsDTG + 3TC FDC

Overview

Phase: Phase 3
Intervention: DTG + 3TC FDC
Conditions: HIV Infections
Sponsor: ViiV Healthcare
Enrollment: 32
Locations: 1
Primary Endpoint: Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Less Than 50 Copies Per Milliliter (c/mL) at Week 48
Status: Completed
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

First-line antiretroviral regimens are highly efficacious and generally well tolerated. However, as these regimens need to be taken life-long, there is growing concern about long-term toxicities associated with these regimens. Thus, there is great interest from participants and clinicians in unique regimens that might avoid such toxicities by minimizing the number of antiretrovirals without sacrificing long-term antiviral efficacy. DTG plus 3TC is a novel, well-tolerated first-line regimen for HIV-infected treatment- naive participants, limiting the risk of many common adverse reactions associated with other antiretroviral drugs. This study was designed to evaluate the efficacy and safety of DTG/3TC as an FDC in ART-naive HIV-1-infected adolescents who weighed at least 25 kilograms (kg).

The study consisted of a Screening Phase (up to 28 days prior to the first dose of drug), followed by a Treatment Phase (up to 48 weeks). Participants who successfully completed 48 weeks of therapy and continued to receive benefit from DTG/3TC FDC were eligible to enter a 96-week Extension Phase. Study participants who successfully completed both the Treatment Phase through 48 weeks and the Extension Phase through 144 weeks and continued to receive benefit from this two-drug regimen were to continue receiving DTG/3TC FDC in a Continuation Phase (after Week 144) until DTG and 3TC were both locally approved for use as part of a dual regimen and the single entities of DTG and 3TC were available to participants (e.g., through public health services), or the DTG/3TC FDC tablet, if required by local regulations, was locally approved and available (e.g., commercially or through public health services), or the participant no longer derived clinical benefit, or the participant met a protocol-defined reason for discontinuation.

All participants received the FDC of DTG/3TC (50/300 milligrams) once daily.

Registry

clinicaltrials.gov

Start Date

May 6, 2019

End Date

May 22, 2025

Last Updated

4 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

ViiV Healthcare

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•HIV-1-infected adolescents were 12 to \<18 years of age at the time of signing the informed consent form.
•Weight was \>25 kg at the time of signing the informed consent form.
•Screening plasma HIV-1 RNA was between 1,000 and =500,000 c/mL.
•Participants were antiretroviral-naive (defined as having had no prior therapy with any antiretroviral agent for the treatment of HIV following a diagnosis of HIV-1 infection). Participants who had received ART for prevention of mother-to-child transmission of HIV in the first 3 months of life were allowed. Participants who had received HIV post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) in the past were allowed as long as the last PEP/PrEP dose was = 6 months before HIV diagnosis or there was documented HIV seronegativity at least 2 months after the last prophylactic dose and prior to the date of HIV diagnosis.
•Male and female participants were included. A female participant was eligible to participate if she was not pregnant (as confirmed by a negative serum human chorionic gonadotropin \[hCG\] test at Screening and a negative urine hCG test before Enrollment) and not lactating. Female participants of child-bearing potential who were engaging in sexual activity that could have led to pregnancy had to agree to use one birth-control method from 28 days prior to the first dose of study medication until 4 weeks after the last dose of study medication (and completion of the follow-up visit). Condoms were additionally recommended, as appropriate use was the only contraceptive method effective in preventing HIV-1 transmission. The investigator was responsible for ensuring that participants understood how to properly use these contraceptive methods. All participants in the study were also counseled on safer sexual practices, including the use and benefit/risk of effective barrier methods (e.g., male condoms), as well as on the risk of HIV transmission to an uninfected partner.
•The participant's parent(s) or legal guardian, or the participant, was capable of giving signed informed consent.

Exclusion Criteria

•Females who were breastfeeding or who planned to become pregnant or breastfeed during the study were excluded.
•Any evidence of active Centers for Disease Control and Prevention (CDC) Stage 3 and/or Category C or World Health Organization (WHO) Stage 4 disease-except cutaneous Kaposi's sarcoma not requiring systemic therapy-and historical or current CD4 cell counts \<200 cells/mm³ or CD4 percent \<15 percent resulted in exclusion.
•Participants with severe hepatic impairment (Class C) as determined by the Child-Pugh classification were excluded.
•Participants with unstable liver disease (defined by ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, or known biliary abnormalities (except Gilbert's syndrome or asymptomatic gallstones) were excluded.
•Evidence of hepatitis B virus (HBV) infection at Screening led to exclusion as follows: participants positive for HBsAg were excluded; participants negative for anti-HBs but positive for anti-HBc (negative HBsAg) and positive for HBV DNA were excluded. Participants positive for anti-HBc (negative HBsAg) and anti-HBs (past and/or current evidence) were immune to HBV and were not excluded.
•Participants with an anticipated need for any HCV therapy during the first 48 weeks of the study-and for any HCV therapy based on interferon or drugs with potential adverse drug-drug interactions with study treatment throughout the entire study period-were excluded.
•Untreated syphilis infection (positive rapid plasma reagin \[RPR\] at Screening without clear documentation of treatment) resulted in exclusion. Participants who were at least 24 hours post-completed treatment were eligible.
•Participants with a history of sensitivity to any study medication or its components, or to drugs of the same class, or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicated participation, were excluded.
•Participants with ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, resected non-invasive cutaneous squamous cell carcinoma, or cervical, anal, or penile intraepithelial neoplasia were excluded. Other localized malignancies required agreement between the investigator and Study Medical Monitor for inclusion.
•Participants who, in the investigator's judgment, posed a significant suicide risk were excluded. A recent history of suicidal behavior and/or suicidal ideation could have been considered evidence of serious suicide risk.

Arms & Interventions

DTG/3TC FDC

Participants received dolutegravir/lamivudine (DTG/3TC) (50/300 mg) Fixed Dose Combination (FDC) tablets orally once daily.

Intervention: DTG + 3TC FDC

Outcomes

Primary Outcomes

Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Less Than 50 Copies Per Milliliter (c/mL) at Week 48

Time Frame: Week 48

Percentage of participants with plasma HIV-1 RNA \<50 c/mL was assessed at Week 48 according to the Food and Drug Administration (FDA) snapshot algorithm.

Secondary Outcomes

Percentage of Participants With Plasma HIV-1 RNA <200 c/mL at Week 24(Week 24)
Percentage of Participants With Plasma HIV-1 RNA <200 c/mL at Week 96(Week 96)
Percentage of Participants With Plasma HIV-1 RNA <200 c/mL at Week 144(Week 144)
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24(Week 24)
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96(Week 96)
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 144(Week 144)
Percentage of Participants With Plasma HIV-1 RNA <200 c/mL at Week 48(Week 48)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Through 144 Weeks(Up to 144 weeks)
Number of Participants With AEs Through 144 Weeks by Severity(Up to 144 weeks)
Number of Participants With Abnormal Findings for Hematology Parameters Through 144 Weeks(Up to 144 weeks)
Number of Participants With Abnormal Findings for Clinical Chemistry Parameters Through 144 Weeks(Up to 144 weeks)
Number of Participants With Abnormal Findings for Fasting Lipids Through 144 Weeks(Up to 144 weeks)
Number of Participants With Abnormal Findings for Urinalysis Parameters Through 144 Weeks(Up to 144 weeks)
Number of Participants Who Discontinue Treatment Due to Adverse Events Through 144 Weeks(Up to 144 weeks)
Number of Participants With Adverse Events and Serious Adverse Events Through 96 Weeks(Up to 96 weeks)
Number of Participants With Severity of Adverse Events Through 96 Weeks(Up to 96 weeks)
Number of Participants With Abnormal Findings for Hematology Parameters Through 96 Weeks(Up to 96 weeks)
Number of Participants With Abnormal Findings for Clinical Chemistry Parameters Through 96 Weeks(Up to 96 weeks)
Number of Participants With Abnormal Findings for Fasting Lipids Through 96 Weeks(Up to 96 weeks)
Number of Participants With Abnormal Findings for Urinalysis Parameters Through 96 Weeks(Up to 96 weeks)
Number of Participants Undergoing Viral Load Monitoring From Week 48 Through 144 Weeks(Weeks 48, 60, 72, 84, 96, 108, 120, 132, and 144)
Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count at Weeks 24 and 48(Baseline (Day 1) and Weeks 24 and 48)
Change From Baseline in CD8+ Cell Count at Weeks 24 and 48(Baseline (Day 1) and Weeks 24 and 48)
Change From Baseline in Ratio of CD4+ and CD8+ at Weeks 24 and 48(Baseline (Day 1) and Weeks 24 and 48)
Number of Participants With Disease Progression From Week 24 Through Week 48(Week 24 and up to Week 48)
Number of Participants With Any Adverse Events and Serious Adverse Events From Week 24 Through Week 48(Week 24 and up to Week 48)
Number of Participants With Severity of Adverse Events From Week 24 Through Week 48(Week 24 and up to Week 48)
Number of Participants With Abnormal Findings for Hematology Parameters From Week 24 Through Week 48(Week 24 and up to Week 48)
Number of Participants With Abnormal Findings for Clinical Chemistry Parameters From Week 24 Through Week 48(Week 24 and up to Week 48)
Number of Participants With Abnormal Findings for Fasting Lipids From Week 24 Through Week 48(Week 24 and up to Week 48)
Number of Participants With Abnormal Findings for Urinalysis Parameters From Week 24 Through Week 48(Week 24 and up to Week 48)
Number of Participants Who Discontinued Treatment Due to Adverse Events From Week 24 Through Week 48(Week 24 and up to Week 48)
Maximum Observed Plasma Concentration (Cmax) Following Dosing With DTG and 3TC(Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1)
Time of Maximum Observed Plasma Concentration (Tmax) Following Dosing With DTG and 3TC(Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1)
Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) Following Dosing With DTG and 3TC(Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1)
Area Under the Curve (AUC) Over the Dosing Interval (AUC[0-tau]) Following Dosing With DTG and 3TC(Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1)
Apparent Terminal Half-life (t1/2) Following Dosing With DTG and 3TC(Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1)
Observed Pre-dose Plasma Concentration Following Dosing With DTG and 3TC(Pre-dose at Week 1)
Observed Plasma Concentration at 24 Hours Following Dosing With DTG and 3TC(24 hours post-dose at Week 1)
Number of Participants With Observed Genotypic Resistance to DTG and 3TC(Up to 144 weeks)
Number of Participants With Observed Phenotypic Resistance to DTG and 3TC(Up to 144 weeks)