IMPAACT 2017

Phase I/II Study of the Safety, Acceptability, Tolerability, and Pharmacokinetics of Oral and Long-Acting Injectable Cabotegravir and Long-Acting Injectable Rilpivirine in Virologically Suppressed HIV-Infected Children and Adolescents

Rationale

The IMPAACT 2017 is a Phase I/II study being conducted to establish if adolescents (and later younger children), infected with HIV-1 who are currently virologically suppressed on ART, remain suppressed upon switching to a two-drug intramuscular (IM) long-acting (LA) regimen of CAB LA plus RPV LA. The initial age group studied will be adolescents aged 12 to < 18 years and results from this initial age cohort may inform the study details in a protocol amendment at a later date for a younger population.

Primary Objectives

Cohort 1 (continuing a background cART regimen)

• To confirm the doses for oral CAB followed by injectable CAB LA in HIV-infected, virologically suppressed adolescents by evaluating:

1. Safety and multiple dose PK of oral CAB through Week 4;

2. 2.1.1.2 Safety and multiple dose PK of CAB LA through Week 16.

• To confirm doses for injectable RPV LA in HIV-infected, virologically suppressed adolescents by evaluating safety and multiple dose PK of RPV LA through Week 16

Cohort 2 (discontinuing a background cART regimen)

• To assess the safety of CAB LA + RPV LA through Week 24 in HIV-infected, virologically suppressed adolescents.

Primary Endpoint/Outcome

Safety through Week 4 for oral CAB, through Week 16 (CAB LA or RPV LA) for Cohort 1

Safety Outcome: All adverse events, regardless of grade

• Number of participants who:

1. Had Grade 3 or higher adverse events

2. Had Grade 3 or higher adverse events assessed as related to study product/s

3. Had serious adverse events meeting ICH criteria assessed as related to study product/s

4. Permanently discontinued study product due to adverse events assessed as related to study product/s

5. Died due to adverse events assessed as related to study product/s Safety through Week 24 for CAB LA+RPV LA for Cohort 2

Safety Outcome: All adverse events, regardless of grade

• Number of participants who:

1. Had Grade 3 or higher adverse events

2. Had Grade 3 or higher adverse events assessed as related to study product/s

3. Had serious adverse events meeting ICH criteria assessed as related to study product/s

4. Permanently discontinued study product due to adverse events assessed as related to study product/s

5. Died due to adverse events assessed as related to study product/s

Study Design

This is a Phase I/II, multi‐center, open‐label, non‐comparative study to confirm the dose and evaluate the safety, tolerability, acceptability, and PK of oral CAB, long-acting injectable CAB (CAB LA), and long-acting injectable RPV (RPV LA) among up to 155 virologically suppressed HIV‐1 infected children and adolescents aged 12 to < 18 years.

Up to 60 parents/caregivers of adolescent participants will also be enrolled to take part in in-depth qualitative interviews.

The study design includes two cohorts of participants and two steps of study participation in each cohort.

Cohort 1, Step 1 and Cohort 2, Step 3 are both a lead-in phase in which participants will receive oral formulations of the study products for at least 4 weeks, and up to 6 weeks (maximum). In Cohort 1, Step 2 and Cohort 2, Step 4, participants will receive injectable formulations of the study products. In each cohort, participants will enter the study in the oral lead-in phase (Step 1, or Step 3) and then transition to the injectable phase (Step 2, or Step 4) if eligibility criteria for the injectable phase are met. Cohort 1 Step 2 and Cohort 2 Step 4 participants, including those who prematurely permanently discontinue injectable study product, will continue on-study for an additional 48 weeks after their last study product injection, per the long-term safety and washout PK follow-up (LSFU) schedule.

Study Population

HIV‐1 infected children and adolescents, 12 to < 18 years

Investigators

• Dr Faeezah Patel, Principal Investigator

• Prof Lee Fairlie, Sub Investigator

• Dr Masebole Masenya, Sub Investigator

• Dr Elizea Horne, Sub Investigator

Sponsors/Donors

The National Institute of Allergy and Infectious Diseases (NIAID)

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Latest Update: 23 August 2021

For more about IMPAACT 2017 please email rhicomms@wrhi.ac.za