THINK’s first paediatric study, sponsored by Janssen Pharmaceuticals, started in May 2015 headed by Dr Ronelle Moodliar at the King Dinuzulu clinical trial site. The study was supported by Seshni Moorgas as the trial coordinator together with Nokuthula Ngcobo and Lungile Phakatias the research nurses. The study contributed towards more than 50% of the total recruited patients globally for cohorts 1 and 2 (>5 to <18 years) and is currently enrolling children into the >2 to <5-year cohort. Through the successful achievements of this study thus far, the paediatric dosage and formulation for the age groups of 5-18-years have now been FDA approved, incorporated internationally into treatment guidelines and published in a leading journal for lung health. Having a paediatric formulation and dosage for bedaquiline has been a huge stride for paediatric clinical practice towards making an all-oral, shortened DR-TB regimen available for children.
Date: 1 September 2021
BACKGROUND: TMC207-C211 (NCT02354014) is a Phase 2, open-label, multicentre, single-arm study to evaluate pharmacokinetics, safety/tolerability, antimycobacterial activity and dose selection of bedaquiline (BDQ) in children (birth to <18 years) with multidrug-resistant-TB (MDR-TB).
METHODS: Patients received 24 weeks’ BDQ with an anti-MDR-TB background regimen (BR), followed by 96 weeks of safety follow-up. Results of the primary analysis are presented based on data up to 24 weeks for Cohort 1 (≥12–<18 years; approved adult tablet at the adult dosage) and Cohort 2 (≥5–<12 years; age-appropriate 20 mg tablet at half the adult dosage).
RESULTS: Both cohorts had 15 patients, of whom respectively 53% and 40% of Cohort 1 and Cohort 2 children had confirmed/probable pulmonary MDR-TB. Most patients completed 24 weeks´ BDQ/BR treatment (Cohort 1: 93%; Cohort 2: 67%). Geometric mean BDQ area under the curve 168h values of 119,000 ng.h/mL (Cohort 1) and 118,000 ng.h/mL (Cohort 2) at Week 12 were within 60–140% (86,200–201,000 ng.h/mL) of adult target values. Few adverse event (AE) related discontinuations or serious AEs, and no QTcF >460 ms during BDQ/BR treatment or deaths occurred. Of MGIT-evaluable patients, 6/8 (75%) Cohort 1 and 3/3 (100%) Cohort 2 culture converted.
CONCLUSION: In children and adolescents aged ≥5–<18 years with MDR-TB, including pre-extensively drug-resistant-TB (pre-XDR-TB) or XDR-TB, 24 weeks of BDQ provided a comparable pharmacokinetic and safety profile to adults.
Keywords: BDQ/TMC207; MDR-TB; children/adolescents; pharmacokinetics; safety/
Affiliations: 1: Tuberculosis and HIV Investigative Network, King Dinuzulu Hospital, Sydenham, Durban, South Africa 2: National Medical Research Center for Phthisiopulmonology and Infectious Diseases, Moscow, Russian Federation 3: De La Salle Health Sciences Institute, Dasmariñas City, Cavite, the Philippines 4: Janssen Research & Development, Leiden, The Netherlands 5: Janssen Pharmaceutica, Beerse, Belgium 6: Janssen Research & Development, Raritan, NJ 7: Janssen Research & Development, Titusville, NJ, IQVIA, NC 8: Janssen Research & Development, Titusville, NJ 9: Johnson & Johnson Global Public Health, New Brunswick, NJ, USA