Safety and Efficacy of Dolutegravir/Lamivudine (DTG/3TC) in Therapy-naive Human Immunodeficiency Virus-1 (HIV-1) Infected Adolescents
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: DTG + 3TC FDC
Intervention description: DTG + 3TC FDC will be available as 50/300 milligrams tablet to be given orally once daily.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: All participants will receive the FDC of DTG/3TC (50/300 milligrams) for once daily dosing in this single arm study.
Masking: None (Open Label)
Masking description: This will be an open-label study. Hence, there will be no masking.
Enrollment: 32.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Viral load; Dolutegravir; Lamivudine; HIV-1; Fixed dose combination; DOVATO

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. Thus, this study is designed to evaluate the efficacy and safety of DTG/3TC as a FDC,
      in ART-naive HIV-1-infected adolescents, who weigh at least 25 kilograms (kg). The study will
      consists of Screening Phase (up to 28 days prior to the first dose of drug) followed by
      Treatment Phase (up to 48 weeks). Participants who successfully complete 48 weeks of therapy
      and who continue to receive benefit from DTG/3TC FDC may enter a 96 weeks study Extension
      Phase. Study participants who have successfully completed both the Treatment Phase through 48
      weeks and the Extension Phase through 144 weeks and continue to receive benefit from this
      two-drug regimen will continue to receive DTG/3TC FDC in a Continuation Phase (after Week
      144) until: DTG and 3TC are both locally approved for use as part of a dual regimen and the
      single entities of DTG and 3TC are available to participants (e.g. through public health
      services), or the DTG/3TC FDC tablet, if required by local regulations, is locally approved
      and available (e.g. commercially or through public health services), or the participant no
      longer derives clinical benefit or the participant meets a protocol-defined reason for
      discontinuation. All participants will receive the FDC of DTG/3TC (50/300 milligrams) for
      once daily. Approximately 30 participants will be enrolled in the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infected adolescents >=12 to <18 years of age at the time of signing the
             informed consent form.

          -  Weight >=25 kg at the time of signing the informed consent form.

          -  Screening plasma HIV-1 RNA between 1,000 and <=500,000 c/mL.

          -  Antiretroviral-naive (defined as no prior therapy with any antiretroviral agent for
             the treatment of HIV following a diagnosis of HIV-1 infection). Participants who
             received ART for prevention of mother to child transmission of HIV in the first 3
             months of life are allowed. Participants who received HIV post-exposure prophylaxis
             (PEP) or pre-exposure prophylaxis (PrEP) in the past are allowed as long as the last
             PEP/PrEP dose was >6 months from HIV diagnosis or there is documented HIV
             seronegativity at least 2 months after the last prophylactic dose and prior to the
             date of HIV diagnosis.

          -  Male and female participants will be included. A female participant is eligible to
             participate if she is not pregnant (as confirmed by a negative serum human chorionic
             gonadotrophin [hCG] test at Screening and negative urine hCG test before Enrollment)
             and not lactating. Female participants who are of child bearing potential and who are
             engaging in sexual activity that could lead to pregnancy, must agree to use one of the
             birth control method from 28 days prior to the first dose of study medication, and
             until 4 weeks after the last dose of study medication (and completion of the follow-up
             visit). Condoms are recommended in addition, because their appropriate use is the only
             contraception method effective for preventing HIV-1 transmission. The investigator is
             responsible for ensuring that participants understand how to properly use these
             methods of contraception. All participants participating in the study should also be
             counselled on safer sexual practices, including the use and benefit/risk of effective
             barrier methods (example given [e.g.] male condom), and on the risk of HIV
             transmission to an uninfected partner.

          -  The participant's parent(s) or legal guardian or the participant is capable of giving
             signed informed consent.

        Exclusion Criteria:

          -  Females who are 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
             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 less than 200 cells per cubic millimeter (cells/mm^3) or CD4 percent <15
             percent.

          -  Participants with severe hepatic impairment (Class C) as determined by Child-Pugh
             classification.

          -  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).

          -  Evidence of hepatitis B virus (HBV) infection based on the results of testing at
             Screening for HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface
             antibody (anti-HBs or HBsAb), 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.

          -  Anticipated need for any HCV therapy during the first 48 weeks of the study and for
             HCV therapy based on interferon or any drugs that have a potential for adverse drug:
             drug interactions with study treatment throughout the entire study period.

          -  Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without
             clear documentation of treatment). Participants who are at least 24 hours post
             completed treatment are eligible.

          -  History or sensitivity to any of the study medications or their components or drugs of
             their class, or a history of drug or other allergy that in the opinion of the
             Investigator or Medical Monitor contraindicates participation.

          -  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; other localized malignancies require agreement between the
             investigator and the Study Medical Monitor for inclusion of the participant.

          -  Participants who in the investigator's judgment, poses a significant suicidality risk.
             Recent history of suicidal behavior and/or suicidal ideation may be considered as
             evidence of serious suicide risk.

          -  Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

          -  Treatment with any of the following agents within 28 days of Screening, radiation
             therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.

          -  Treatment with any agent with documented activity against HIV-1 in vitro within 28
             days of first dose of study treatment.

          -  Receipt of any prohibited medication and inability or unwillingness to switch to an
             alternative medication.

          -  Exposure to an experimental drug or experimental vaccine within either 28 days, 5
             half-lives of the test agent, or twice the duration of the biological effect of the
             test agent, whichever is longer, prior to the first dose of study treatment.

          -  Any evidence of pre-existing viral resistance based on the presence of any major
             resistance-associated mutation in the Screening result or, if known, in any historical
             resistance test result.

          -  Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during
             the Screening period to verify a result.

          -  Any acute laboratory abnormality at Screening, which, in the opinion of the
             Investigator, would preclude the participant's participation in the study of an
             investigational compound.

          -  ALT >=5 times the upper limit of normal (ULN) or ALT >=3 times ULN and bilirubin >=1.5
             times ULN (with >35 percent direct bilirubin).

          -  Creatinine clearance of <50 milliliters per minute per 1.73 square meter (mL/min/1.73
             m^2) using the Schwartz equation method.

          -  Children who are wards of the state or government.