Preliminary results from first paediatric raltegravir study
Polly Clayden, HIV i-Base
Adrew Wiznia and coworkers from IMPAACT P1066 showed preliminary results from the first paediatric study of raltegravir (RAL).
This is an ongoing prospective, non-randomised, open label, dose-finding trial of RAL plus optimised background regimen (OBR) in treatment-experienced children.
Children aged >12 to <19 years (cohort 1) and >6 to to <12 years (cohort IIA). The children are enrolled sequentially older to younger.
Children in stage I received RAL poloxamer film tablets that were added to a stable, failing ART regimen. Pharmacokinetics (PK) was done on day 7 to 12 and then OBR started.
The study had enrolled 36 patients (22 in cohort I and 14 in cohort IIA. They initially received a 6 or 8mg/kg dose bid with a maximum dose of 600mg bid.
The study demographics included: 47% male, 67% black, and 25% white. Median baseline viral load was 4.4 log (range 3.1 to 5.9) copies/mL and were similar between the cohorts. Median CD4 percentage was 22 (range 0 to 42%).
Six children had grade 3/4 adverse events: 5 had neutropenia, 1 increased lipids, and 1 increased creatinine associated with aminoglycoside use. One grade 4 neutropenia and one elevated GGT was possibly associated with RAL.
There were no deaths. Four children were withdrawn from the study, 3 because of poor adherence (cohort 1) and one at the request of the doctor (cohort IIA).
In an intent-to-treat analysis of those treated at 8 mg/kg 23/30 (77%) and 24 of 14/30 (86%) were <400 copies/mL (50% and 63% <50 copies/mL) at weeks 8 and 12 respectively. Median CD4 percentage was 24% at both timepoints.
The investigators wrote: Preliminary, short-term and partial data from IMPAACT P1066 suggests that RAL + OBR in children ages 6 to 18 was generally safe, well tolerated and effective. Enrollment into these cohorts, as well as use of a chewable formulation for children <12 years of age, is continuing.
For cohort IIA, repeat PK and safety evaluations at a uniform dose of 400 mg bid regardless of weight is ongoing.
Merck will continue this paediatric programme with sequential age strata down to 4 weeks of age.
In addition to the chewable formulation, oral granules for suspension are planned for children less than two years old.
Wiznia A et al. Safety and efficacy of raltegravir in pediatric HIV infection. Preliminary analysis from the International Maternal Pediatric Adolescent AIDS Clinical Trials group, P1066. 16th CROI, February 2009, Montreal, Canada. Poster abstract 874.