More Options for Children and Adolescents (MOCHA): Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in HIV-Infected Children and Adolescents

Exclusion Criteria

• •Adolescents will be excluded from the study if any of the following are identified during the screening period:
• •Within 6 months (defined as within 179 days) prior to entry, two consecutive documented HIV-1 RNA values greater than the lower limit of detection of the assay
• •* Note: Unconfirmed virologic HIV-1 RNA value of greater than the lower limit of detection of the assay (transient detectable viremia, or "blip") prior to screening is not exclusionary.
• •For Cohort 1 participants enrolling to Cohort 2, Step 3, occurrence of any Grade 3 or higher adverse event assessed as related to study product or permanent discontinuation of study product due to an adverse event of any grade assessed as related to study product during participation in Cohort 1 (including any long-term safety and washout PK follow-up visits).
• •For participants enrolling to Cohort 1 Step 1, based on available medical records, currently on either a cART regimen containing both a protease inhibitor (PI) and an integrase strand transfer inhibitor (INSTI), or a cART regimen containing both an INSTI and a non-nucleoside reverse transcriptase inhibitor (NNRTI).
• •As determined by the IoR or designee, and based on available medical records, known or suspected resistance to RPV
• •As determined by the IoR or designee based on available medical records, known or suspected resistance to INSTIs
• •History of congestive heart failure, symptomatic arrhythmia, or any clinically significant cardiac disease, as determined by the IoR or designee based on available medical records
• •At entry, known active tuberculosis infection, requiring anti-tuberculosis treatment, as determined by the IoR or designee based on available medical records
• •Known hepatitis B or hepatitis C infection, as determined by the IoR or designee based on available medical records
• •Clinically significant hepatic disease, as determined by the IoR or designee based on available medical records
• •Current or anticipated need for chronic anti-coagulation, as determined by the IoR or designee, based on available medical records
• •History of sensitivity to heparin or heparin-induced thrombocytopenia, as determined by the IoR or designee, based on available medical records
• •History of known or suspected bleeding disorder including history of prolonged bleeding, as determined by the IoR or designee, based on available medical records
• •Known or suspected allergy to study product components
• •More than one seizure within one year (defined as within 365 days) prior to entry, or unstable or poorly controlled seizure disorder, as determined by the IoR or designee, based on available medical records.
• •At entry, participant is receiving (or has received in the last 7 days) any disallowed medication listed in the study protocol.
• •Current inflammatory skin condition that compromises the safety of intramuscular injections as determined by the IoR or designee.
• •Has a tattoo or other dermatological condition overlying the buttock region which, in the opinion of the IoR or designee, may interfere with interpretation of injection site reactions
• •Surgically-placed, or planned, buttock implants, per self-report
• •For females, lactating (per self-report and/or parent/guardian report) at entry
• •Enrolled in another clinical trial of an investigational agent, device, or vaccine
• •Any other condition or social circumstance situation that, in the opinion of the IoR or designee, would make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
• •Cohort 1 Step 1 participants 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 Cohort 1 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. See the study protocol for Week 4a and Week 4b visit scheduling, order of procedures, and visit windows, respectively.
• •All of the following criteria must be met in order for participants to be included in Cohort 1 Step 2:
• •Currently enrolled in Cohort 1, Step 1
• •At Cohort 1 Step 1 Week 4a study visit, or from confirmatory repeat testing of Cohort 1 Step 1 Week 4a study visit laboratory tests, has Grade 2 or lower of all the following laboratory test results:
• •* ALT (u/l)
• •* Lipase (u/l)
• •* Estimated creatinine clearance (CrCl; Schwartz formula mL/min/1.73m\^2)
• •* Platelets (cells/mm\^3)
• •* Hemoglobin (g/dL)
• •* AST (u/l)
• •* Absolute Neutrophil Count (cells/mm3)
• •* Note: For a Grade 2 ALT test result from this visit, refer to the study protocol for required participant management. Abnormal laboratory test result values from the Week 4a visit may be repeated within the target visit window, and if confirmatory testing results in Grade 2 or lower, the participant may be eligible to continue onto the injection phase, should all other eligibility criteria be met.
• •For females, at Cohort 1 Step 1 Week 4b study visit, has a negative hCG laboratory test result
• •Assessed by the IoR or designee as sufficiently adherent 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
• •Participants who meet any of the following criteria will be excluded from Cohort 1 Step 2:
• •* Has permanently discontinued oral study product
• •* Occurrence of any grade 3 or higher adverse event assessed as related to study product during participation in Step 1
• •* Any other condition or social circumstance that, in the opinion of the IoR or designee, would make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
• •Cohort 2 Step 3 participants will be assessed for eligibility to progress from the oral lead-in phase (Step 3) to the injection phase (Step 4) primarily based on the safety assessments from the Cohort 2 Step 3 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. See the study protocol for Week 4a and Week 4b visit scheduling, order of procedures, and target visit windows, respectively.
• •All of the following criteria must be met in order for participants to be included in Cohort 2 Step 4:
• •Currently enrolled in Cohort 2, Step 3
• •At Cohort 2 Step 3 Week 4a study visit, or from confirmatory repeat testing of Cohort 2 Step 3 Week 4a study visit laboratory tests, has Grade 2 or lower of the following laboratory test results:
• •* ALT (u/l)
• •* Lipase (u/l)
• •* Estimated creatinine clearance (CrCl; Schwartz formula mL/min/1.73m\^2)
• •* Platelets (cells/mm\^3)
• •* Hemoglobin (g/dL)
• •* AST (u/l)
• •* Absolute Neutrophil Count (cells/mm3)
• •* Note: For a Grade 2 ALT test result from this visit, refer to the study protocol for required participant management. Abnormal laboratory test result values from the Week 4a visit may be repeated, within the target visit window, and if confirmatory testing results in Grade 2 or lower, the participant may be eligible to continue onto the injection phase, should all other eligibility criteria be met.
• •For females, at Cohort 2 Step 3 Week 4b study visit, has a negative hCG laboratory test result
• •Assessed by the IoR or designee as sufficiently adherent in Step 3 to permit an adequate evaluation of safety and tolerability as part of the oral lead-in phase prior to entry into the injection phase
• •Participants who meet any of the following criteria will be excluded from Cohort 2 Step 4:
• •* Has permanently discontinued oral study products
• •* Occurrence of any grade 3 or higher adverse event assessed as related to study product during participation in Cohort 2, Step 3
• •* Any other condition or social circumstance that, in the opinion of the IoR or designee, would make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
• •Selected parents or caregivers of adolescents may be enrolled to complete qualitative phone interviews. See the study protocol for more information regarding the selection process, and coordination of scheduling the interviews. All of the following criteria must be met for the parent/caregiver to be enrolled:
• •Selected by the protocol team for participation in the study
• •Willing and able to provide informed (verbal or written) consent for study participation
• •Per the adolescent participant, has knowledge of how the adolescent participant tolerated the study product, and lives with or has regular supportive contact with the adolescent participant
• •Per parent/caregiver self-report, has knowledge of how the participant tolerated the study product, and lives with or has regular supportive contact with the adolescent participant
• •Willing and able to complete interview in English by phone
• •Parents and/or caregivers of participants who meet the following criterion will be excluded from study participation:
• •* Any condition or social circumstance that, in the opinion of the IoR or designee, would make study participation unsafe for either the parent/caregiver or the adolescent participant, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.