Study of Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living With HIV-1, Two to Less Than 12 Years of Age

Parent or legal guardian is willing and able to provide written permission for child's study participation and, when applicable per institutional review board/ethics committee (IRB/EC) policies and procedures, child is willing and able to provide written assent for study participation.

Note: All sites must follow all applicable IRB/EC policies and procedures; for US sites, this includes single IRB (sIRB) policies and procedures.

Age two years old to less than 12 years old at entry

Body weight ≥10 kg and \<40 kg at entry

At entry, willing and able to comply with the study visit schedule and other study requirements, as determined by the site investigator or designee.

Confirmed HIV-1-infection based on documented testing of two samples collected from two separate blood collection tubes per Sample #1 and Sample #2 requirements. Test results may be obtained from medical records or from testing performed during the study screening period

Has been on a stable unchanged ART regimen consisting of two or more drugs from two or more antiretroviral drug classes for at least six consecutive months (defined as 180 consecutive days) prior to entry.

Has no prior history of switching ART regimens for reasons related to treatment failure based on parent/guardian report and/or available medical records.

Note: Participants undergoing dose modifications for growth or who have switched to a new formulation due to toxicity, tolerability, or changes in national treatment guidelines are considered eligible per this inclusion criterion. Treatment failure should be defined by local guidelines.

From a specimen collected less than six months (defined as within 179 days) prior to entry, has at least one of the following documented plasma HIV-1 RNA results:

* \<50 copies/mL, or

* less than the lower limit of detection of the assay

From a specimen collected in the 6-18 months (defined as 180 to 545 days) prior to entry, has at least one of the following documented plasma HIV-1 RNA results:

* \<50 copies/mL, or

* less than the lower limit of detection of the assay

At screening, a documented plasma HIV-1 RNA \<50 copies/mL.

Note: HIV-1 RNA test results at screening cannot be used to satisfy previously listed inclusion criterion. If participant does not have a documented HIV-1 RNA test result at screening that satisfies previously listed criteria, they should be referred for standard of care testing and return at a later date for screening.

Has normal, Grade 1, or Grade 2 results for all the following laboratory tests at screening (i.e., within 28 days prior to entry) based on grading per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events:

* AST (\<5.0 x ULN)

* ALT (\<5.0 x ULN)

* Total bilirubin (\<2.6 x ULN)

* Lipase (\<3 x ULN)

* Estimated glomerular filtration rate (eGFR; ≥60 ml/min/1.73 m2)

* Platelets (≥50,000 cells/mm3 or ≥50.00 x 109 cells/L)

* Hemoglobin (≥8.5 g/dL or ≥5.25 mmol/L)

* Neutrophils (≥600 cells/mm3)

Note: Laboratory tests may be repeated during the study screening period (i.e., within 28 days prior to entry), with the latest result used for eligibility determination. ALT and total bilirubin should also be assessed

Has no evidence of chronic hepatitis B infection based on hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) testing at screening; any of the following three combinations of test results are acceptable for inclusion:

* HBsAg negative, HBcAb negative, HBsAb negative

* HBsAg negative, HBcAb negative, HBsAb positive

* HBsAg negative, HBcAb positive, HBsAb positive

At screening, has a mean QTc interval (based upon a triplicate reading) less than or equal to 450 msec based on an electrocardiogram (ECG) automated machine readout or calculated using the Fridericia formula.

For female participants of childbearing potential, not pregnant based upon negative blood or urine pregnancy test at entry. Childbearing potential is defined as nine years of age or older and:

* Having reached menarche or

* Engaging in sexual activity (self-reported) that could lead to pregnancy

For female participants of childbearing potential who are engaging in sexual activity (self-reported) that could lead to pregnancy, at entry, currently using at least one allowable highly effective method of contraception and agrees to use at least one allowable highly effective method of contraception throughout study participation and for at least 30 days after last oral product use and 48 weeks after last injectable study product use.

Highly effective methods of contraception include:

Surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy)

Contraceptive intrauterine device or intrauterine system

Subdermal contraceptive implant

Progestogen injections

Combined estrogen and progestogen oral contraceptive pills

Percutaneous contraceptive patch

Contraceptive vaginal ring

All participants enrolled in Cohort 1 or Cohort 2a will be assessed for eligibility to progress from the oral lead-in phase (Step 1) to the injection phase (Step 2), primarily based on the safety assessments from the Step 1 Week 4a study visit. Clinical assessments conducted prior to administering the first injection at the Week 4b visit will also be used to confirm eligibility to receive the injectable study product.

All of the following criteria must be met in order for a participant enrolled in Cohort 1 or Cohort 2a to be included in Step 2

Currently enrolled as a participant in Step 1.

Has normal, Grade 1, or Grade 2 results from all of the following laboratory test results based upon specimens collected at the Week 4a study visit or from confirmatory repeat testing of Week 4a study visit laboratory tests:

* AST (\<5.0 x ULN)

* ALT (\<5.0 x ULN)

* Lipase (\< 3 x ULN)

* Estimated glomerular filtration rate (eGFR; ≥60 ml/min/1.73 m2))

* Platelets (≥50,000 cells/mm3 or ≥50.00 x 109 cells/L)

* Hemoglobin (≥8.5 g/dL or ≥5.25 mmol/L)

* CK (\<10 x ULN)

Note: For a Grade 2 ALT test result from this visit, refer to protocol for required participant management.

For female participants of childbearing potential not pregnant based upon negative blood or urine pregnancy test at the Week 4b study visit.

Assessed by the IoR or designee as sufficiently adherent to study products in Step 1 to permit an adequate evaluation of safety and tolerability as part of the oral lead in phase prior to entry into the injection phase.

Parents/caregivers of participants will be considered for enrollment to complete quantitative behavioral surveys and/or qualitative in-depth interviews (IDIs), as indicated in the SoE. One parent/caregiver per participant should be enrolled to complete all behavioral assessments, including the IDI, when applicable. Informed consent for parent/caregiver enrollment should be obtained at the entry visit, after the child participant's eligibility has been confirmed, and may be completed at a later date, if necessary. However, parent/caregiver consent must occur prior to any study assessments being conducted. The enrolled caregiver may be the different than the parent or legal guardian who provided written permission for the child to participate. If, at any point the enrolled parent/caregiver for a given participant withdraws from the study or is unable to complete remaining study assessments for any reason, they may be replaced.

Caregivers must meet the following criteria to be eligible to enroll in IMPAACT 2036:

18 years of age or older

Able and willing to provide written informed consent consistent with site IRB/EC policies and procedures

Caregiver, defined as a biological parent, legal guardian, or other person who provides significant emotional, psychological, and/or physical care to a child enrolled in IMPAACT 2036, based on self-report

What this study is about