Background
Long-acting cabotegravir (CAB-LA) plus long-acting rilpivirine (RPV-LA) are approved for maintenance of viral suppression in adults and adolescents at least 12 years and 35kgs with HIV-1 infection. IMPAACT 2036 (CRAYON) is a Phase I/II study evaluating oral (PO) and intramuscular (IM) CAB-LA+RPV-LA in virologically suppressed children 2-<12 years, with HIV-1. Here, we present all available data at the interim safety and pharmacokinetic (PK) evaluation, including the first data from children <20kg.
Methods
Children were enrolled into five weight bands (WBs): WB1 (35-<40kg), WB2 (25-<35kg), WB3 (20-<25kg), WB4 (14-<20kg) and WB5 (10-<14kg). After discontinuing all current cART, participants received PO CAB+RPV through W4, followed by IM CAB-LA+RPV-LA injections every 4 weeks (Q4W). PK samples were drawn at W2 (to assess PO dosing), before every injection and at W5, 6, 9 (to assess LA dosing).
Results
61 participants enrolled (8 in WB1, 18 in WB2, 13 in WB3, 9 in WB4 and 13 in WB5). The median (min, max) age and weight at entry were 8 years (2, 11) and 22 kg (10.8, 39.3); 54% were female; 23% were Asian, 62% were Black. Three prematurely discontinued due to withdrawal of consent (n=2) and virological failure on oral CAB+RPV with a peak viral load of 573 copies/ml (n=1). Median (Q1, Q3) time on study was 57 weeks (28, 70).
While on study, 6 (10%) children experienced >Grade 3 adverse event (AE), all of which resolved. One >Grade 3 AE was drug-related (Grade 3 injection-related reaction). Two additional children had Grade 2 injection-related reactions. Injection site pain in 28 children (46%) was the most frequent AE; all were Grade 1 or 2. No AEs led to treatment discontinuation.
51 participants contributed to the PK analysis (Figure 1). WB1-3 PK have been previously reported (M Archary, CROI 2025). In 18 WB4-5 participants, the median (Q1, Q3) AUCs during oral lead-in were 166.0 (133.5, 219.6) mcg*h/mL for CAB-PO and 3856 (2533, 4407) ng*h/mL for RPV-PO. Median (Q1, Q3) pre-dose concentrations at W12 (n=13) were 3.49 (2.67, 4.72) mcg/mL for CAB-LA and 61.3 (49.4, 68.5) ng/mL for RPV-LA. These values met protocol-defined targets for both drugs by PO and IM routes.
Conclusions
Administration of PO CAB+RPV for 4 weeks, followed by IM CAB-LA+RPV-LA Q4W in children weighing 10-<40 kg, achieved plasma concentrations similar to adolescents and adults. No new or unanticipated safety concerns were identified. Grade 1 or 2 injection site pain was the most common AE.
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