Safety and Efficacy of Dolutegravir/Lamivudine (DTG/3TC) in Therapy-naive Human Immunodeficiency Virus-1 (HIV-1) Infected Adolescents

ViiV Healthcare

Status and phase

Completed

Phase 3

Conditions

HIV Infections

Treatments

Drug: DTG + 3TC FDC

Study type

Interventional

Funder types

Industry

Identifiers

NCT03682848

205861

Details and patient eligibility

About

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.

Enrollment

32 patients

Sex

All

Ages

12 to 17 years old

Volunteers

No Healthy Volunteers

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.
Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening resulted in exclusion.
Treatment with radiation therapy, cytotoxic chemotherapeutic agents, or any systemic immune suppressant within 28 days of Screening resulted in exclusion.
Treatment with any agent with documented activity against HIV-1 in vitro within 28 days of the first study dose resulted in exclusion.
Receipt of any prohibited medication, and inability or unwillingness to switch to an alternative medication, resulted in exclusion.
Exposure to an experimental drug or vaccine within 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent (whichever was longer) prior to the first study dose resulted in exclusion.
Any evidence of pre-existing viral resistance based on any major resistance-associated mutation in Screening or historical results led to exclusion.
Any verified Grade 4 laboratory abnormality led to exclusion. A single repeat test during Screening was allowed to verify results.
Any acute laboratory abnormality at Screening that, in the Investigator's opinion, would have precluded participation in the study of an investigational compound resulted in exclusion.
ALT >5× the upper limit of normal (ULN), or ALT >5× ULN with bilirubin >1.5× ULN (with >35 percent direct bilirubin), resulted in exclusion.
Creatinine clearance <50 mL/min/1.73 m² using the Schwartz equation resulted in exclusion.
Children who were wards of the state or government were excluded.