Multi-Centre Phase IV Trial to Investigate the Immunogenicity of a New Liquid Formulation of Recombinant Human Growth Hormone in Adults with Growth Hormone Deficiency
Presentation Number: SAT 432
Date of Presentation: April 1st, 2017
Gudmundur Johannsson*1, Kirsten Nespithal2, Ursula Ploeckinger3, Veronica Alam2 and Mark McLean4
1Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and The Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden, 2Merck Serono, 3Charité-Universitaetsmedizin Berlin, Berlin, Germany, 4University of Western Sydney, Sydney NSW, AUSTRALIA
Background: During drug development, biological products require assessment of their immunological profile. In this case a new liquid formulation for Saizen® was tested as part of a post-approval commitment to the Australian Regulatory Agency (TGA).
Objectives: The primary objective of this open-label, single arm study was to determine whether Saizen solution for injection induces binding antibodies (BAbs) in patients with congenital or adult-onset adult growth hormone deficiency (AGHD). Secondary objectives were: to determine the proportion of subjects with BAbs who also developed neutralising antibodies (NAbs); to assess the overall pharmacodynamic profile in subjects with or without antibodies; to assess the safety of Saizen solution for injection; and to measure treatment adherence.
Methods: Subjects were males or females aged 18–65 years with documented AGHD who were either r-hGH-treatment-naïve or had stopped≥1 month prior to screening. The primary endpoint was the percentage of subjects developing BAbs to Saizen solution at any time during the 39-week treatment course, identified with a bridging electrochemiluminescence assay and confirmed in Saizen-spiked samples. Secondary endpoints were: the proportion of subjects with BAbs who became positive for NAbs (assayed by inhibition of GH receptor transfected cell lines); the effects of Saizen on the GH biomarkers IGF-1, IGFBP-3 and IGF-1 SDS; safety as assessed through the evaluation of treatment emergent adverse events (TEAEs), physical examination, weight, BP, HR changes, and changes in laboratory parameters; and adherence to treatment as documented using easypod™ connect software.
Results: Overall, 78 subjects (61.5% males) started treatment and 68 completed the 39-week treatment period. Mean age was 44.5 years (range 21–65) and the majority (91%) were white. On study entry the majority (82.1%) were treatment-naïve and no subject had BAbs to r-hGH. The median (Q1; Q3) duration of treatment in the study was 273.0 days (267.0 to 277.0), consistent with the study duration and recorded adherence. Overall mean treatment adherence was 89.3%, and 84.6% of subjects had >80% adherence. The proportion of subjects who developed BAbs during the study was 0% (95% CI 0.00 to 4.68); no NAbs were detected. IGF profiles reflected exposure to r-hGH, and IGF-1 SDS increased slightly (range 0.17 to 0.26). 92% of patients reported ≥1 TEAE (mostly mild or moderate); no TEAEs were deemed related to the study drug.
Conclusions: This study confirms the low immunogenicity potential of the liquid formulation for Saizen in adults, in line with immunogenicity data on the Saizen freeze-dried formulation. The IGF-1 profiles confirmed exposure to active r-hGH. The overall safety profile of Saizen liquid formulation appears to be in line with the known profile of Saizen freeze-dried formulation, and no new safety concerns were detected.
Disclosure: KN: Employee, Merck & Co.. UP: , Merck & Co.. VA: Employee, Merck & Co.. Nothing to Disclose: GJ, MM