M A Czepielewski1, Q Garret2, S A C Vencio3, N Rassi4, J S Felicio5, M S Faria6, C C P Senn7, M D Bronstein8, M J A G Cerqueira9, A C L Neves10, J A Sgarbi11, A M Spinola-Castro12, M P R Cunha13, F Bandeira14, O Toffoletto15, J Afiune15, R Baradelli15, D G Rodrigues15, M Scharf7. 1. Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, UFRGS, Porto Alegre, RS, Brazil. Electronic address: mczepielewski@hcpa.edu.br. 2. CEDOES, Vitória, ES, Brazil. 3. ICF - Instituto de Ciências Farmacêuticas de Estudos e Pesquisas Ltda, Aparecida de Goiânia, GO, Brazil. 4. Hospital Alberto Rassi - HGG, Goiânia, GO, Brazil. 5. Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil. 6. Hospital Universitário da Universidade Federal do Maranhão/HU/UFMA, São Luis, MA, Brazil. 7. Centro de Diabetes de Curitiba, Curitiba, PR, Brazil. 8. CPQUALI Pesquisa Clínica Ltda, São Paulo, SP, Brazil. 9. Instituto de Ensino e Pesquisa Clínica do Ceará, Fortaleza, CE, Brazil. 10. Instituto de Medicina Integral Professor Fernando Figueira - IMIP, Recife, PE, Brazil. 11. Unidade de Pesquisa Clínica de Marília Ltda (UpCliM), Marília, SP, Brazil. 12. Universidade Federal de São Paulo - UNIFESP/EPM, São Paulo, SP, Brazil. 13. CAEP - Centro Avançado de Estudos e Pesquisas Ltda, Campinas, SP, Brazil. 14. Centro de Pesquisas Médicas Básica e Clínica Ltda, Recife, PE, Brazil. 15. Cristália Produtos Químicos Farmacêuticos Ltda, Itapira, SP, Brazil.
Abstract
OBJECTIVE: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DESIGN: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received eitherr-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. RESULTS: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. CONCLUSIONS: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.
RCT Entities:
OBJECTIVE: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant humangrowth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DESIGN: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. RESULTS: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. CONCLUSIONS: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.