Safety of and Immune Response to Dolutegravir in HIV-1 Infected Infants, Children, and Adolescents

Completed · Phase 1/Phase 2

Conditions studied: HIV Infections

In brief

Dolutegravir (DTG) is an HIV drug in the integrase inhibitor drug class. This study evaluated the pharmacokinetics (PK), safety, tolerability of and immune response to DTG when used concurrently with optimized background therapy (OBT) in HIV-1 infected infants, children, and adolescents.

Key facts

Study ID

NCT01302847

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

181

Starts

2011-04-20

Expected to finish

2023-10-18

Last updated by the study team

2024-12-12

Who can join

Age: 0 and older, up to 17. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Confirmed HIV-1 infection, defined as positive results from two samples collected at different time points (see protocol for more information)
• Participant belonged to one of the ARV exposure groups below:
• ARV-treatment experienced (not including receipt of ARVs as prophylaxis or for prevention of perinatal transmission)
• Previously took ARVs for treatment, but not taking ARVs at study screening.
• Had been off treatment for greater than or equal to 4 weeks prior to screening, OR
• At screening, taking ARVs for treatment but failing.
• Was on an unchanged, failing therapeutic regimen within the 4 to 12 weeks prior to screening (less than or equal to 1 log drop in HIV-1 RNA within the 4 to 12 weeks prior to screening). OR
• For participants less than 2 years of age, initiated ARVs for treatment less than 4 weeks prior to screening.
• ARV treatment naive (no exposure to ARVs for treatment; could have received ARVs for prophylaxis or prevention of perinatal transmission)
• If an infant had received nevirapine (NVP) as prophylaxis to prevent perinatal transmission, he or she did not receive NVP for at least 14 days prior to enrollment into Stage I or II.
• HIV-1 RNA viral load greater than 1,000 copies/mL of plasma at screening.
• Demonstrated ability or willingness to swallow assigned study medications.
• Parent or legal guardian were able and willing to provide signed informed consent.
• Female participants of reproductive potential, defined as having reached menarche, and who were engaging in sexual activity that could lead to pregnancy, agreed to use two contraceptive methods while on study and for two weeks after stopping study drug.
• Males engaging in sexual activity that could lead to HIV-1 transmission agreed to use a condom.
• Agreed to stay on optimized background therapy (OBT) while on study:
• Participants who at screening were greater than or equal to 2 years of age and ARV-treatment experienced, had at screening at least one fully active drug for the OBT.
• Participants who were greater than or equal to 2 years of age and ARV-treatment naïve, had genotype testing at screening/entry even with results pending.
• Participants less than 2 years of age (either ARV-treatment experienced or ARV treatment naïve), had genotype testing at screening/entry even with results pending.

You may not qualify if…

• Presence of any active AIDS-defining opportunistic infection
• At enrollment, participant less than 3.0 kg
• Known Grade 3 or greater of any of the following laboratory toxicities within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), alanine transaminase (ALT), lipase, serum creatinine and total bilirubin. A single repeat within the 30 days is allowed for eligibility determination. NOTE: Grade 3 total bilirubin was allowable, if the participant was on atazanavir (ATV).
• ANY known Grade 4 laboratory toxicities within 30 days prior to study entry. NOTE: Grade 4 total bilirubin was allowable, if the participant was on ATV.
• The following liver toxicities within 30 days prior to study entry: ALT greater than 3x the upper limit of normal (ULN) AND direct bilirubin was greater than 2x ULN
• Any prior history of malignancy, with the exception of localized malignancies such as squamous cell or basal cell carcinoma of the skin
• Clinical or symptomatic evidence of pancreatitis, as determined by the clinician
• Use of any disallowed medications at time of screening (see the protocol for a complete list of disallowed medications)
• Known history of exposure to integrase inhibitor treatment by the participant or participant's mother prior to delivery/cessation of breastfeeding
• Known resistance to an integrase inhibitor
• Women who were pregnant or breastfeeding
• At screening/entry, participating in or had participated in a study with a compound or device that was not commercially available within 30 days of signing informed consent, unless permission from both Protocol Teams was granted
• Participant was unlikely to adhere to the study procedures, keep appointments, or was planning to relocate during the study to a non-IMPAACT study site
• Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study
• At screening/entry had used, or anticipated using, chronic systemic immunosuppressive agents or systemic interferon (e.g., for treatment of hepatitis C virus [HCV] infection) within 30 days prior to beginning DTG study treatment. Systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg/day) for replacement therapy or short courses (less than or equal to 30 days) were permitted. (See protocol for more information on disallowed medications.)
• Any condition that in the opinion of the site investigator, placed the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.
• Active tuberculosis (TB) disease and/or requirement for treatment that included rifampin at the time of the screening visit. However, participants who needed rifampin treatment while on DTG were allowed to continue in P1093 provided the DTG dose was adjusted according to the protocol.

Where it is running

• University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program (Site ID: 4601) — La Jolla, California, United States
• Miller Children's Hosp. Long Beach CA NICHD CRS (Site ID: 5093) — Long Beach, California, United States
• David Geffen School of Medicine at UCLA NICHD CRS (Site ID: 5112) — Los Angeles, California, United States
• Univ. of California San Francisco NICHD CRS (Site ID: 5091) — San Francisco, California, United States
• Univ. of Colorado Denver NICHD CRS (Site ID: 5052) — Aurora, Colorado, United States
• Howard Univ. Washington DC NICHD CRS (Site ID: 5044) — Washington D.C., District of Columbia, United States
• South Florida CDTC Ft Lauderdale NICHD CRS (Site ID: 5055) — Fort Lauderdale, Florida, United States
• USF - Tampa NICHD CRS (Site ID: 5018) — Tampa, Florida, United States
• Rush Univ. Cook County Hosp. Chicago NICHD CRS (Site ID: 5083) — Chicago, Illinois, United States
• Lurie Children's Hospital of Chicago (LCH) CRS (Site ID: 4001) — Chicago, Illinois, United States
• Children's Hosp. of Boston NICHD CRS (Site ID: 5009) — Boston, Massachusetts, United States
• Boston Medical Center Ped. HIV Program NICHD CRS (Site ID: 5011) — Boston, Massachusetts, United States
• Metropolitan Hosp. NICHD CRS (Site ID: 5003) — New York, New York, United States
• Bronx-Lebanon Hospital Center NICHD CRS (Site ID: 5114) — The Bronx, New York, United States
• Jacobi Med. Ctr. Bronx NICHD CRS (Site ID: 5013) — The Bronx, New York, United States
• DUMC Ped. CRS (Site ID: 4701) — Durham, North Carolina, United States
• Seattle Children's Research Institute CRS (Site ID: 5017) — Seattle, Washington, United States
• Gaborone CRS (Site ID: 12701) — Gaborone, South-East District, Botswana
• Molepolole CRS (Site ID: 12702) — Gaborone, Botswana
• SOM Federal University Minas Gerais Brazil NICHD CRS (Site ID: 5073) — Belo Horizonte, Minas Gerais, Brazil
• Hospital Federal dos Servidores do Estado NICHD CRS (Site ID: 5072) — Rio de Janeiro, Brazil
• Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS (Site ID: 5071) — Rio de Janeiro, Brazil
• Hosp. Geral De Nova Igaucu Brazil NICHD CRS (Site ID: 5097) — Rio de Janeiro, Brazil
• Univ. of Sao Paulo Brazil NICHD CRS (Site ID: 5074) — São Paulo, Brazil
• Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS (Site ID: 5121) — Kericho, Kenya

Full record on ClinicalTrials.gov

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