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

• Published in: Journal of endocrinological investigation Vol. 41; no. 8; pp. 919 - 927
• Main Authors: Johannsson, G., Nespithal, K., Plöckinger, U., Alam, V., McLean, M.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2018; Springer Nature B.V
• Subjects: 1989; acta endocrinologica; adherence; Adult; Adults; Aged; Antibodies; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - immunology; Binding antibodies; Biological Availability; Biomarkers; Biomarkers - analysis; body-composition; children; Endocrinology; Endocrinology & Metabolism; Endocrinology and Diabetes; Endokrinologi och diabetes; Female; Follow-Up Studies; gh replacement therapy; Growth Disorders - drug therapy; Growth Disorders - immunology; Growth Disorders - metabolism; Growth hormones; hgh; Human Growth Hormone - administration & dosage; Human Growth Hormone - immunology; Humans; Immunogenicity; kano k; Lipids - chemistry; Liquid; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Neutralising antibodies; Original; Original Article; p559; Patients; Physical growth; Prognosis; Recombinant human growth hormone; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Safety; v120; Young Adult; Adult growth hormone deficiency; Binding antibodies; Recombinant human growth hormone; Neutralising antibodies; Liquid formulation
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-017-0818-4

Purpose To investigate whether a new liquid formulation of recombinant human growth hormone (r-hGH) induces the production of binding antibodies (BAbs) in adults with congenital or adult-onset growth hormone deficiency (GHD). Methods Men or women aged 19–65 years with adult growth hormone deficiency who were r-hGH-naïve or had stopped treatment ≥ 1 month before screening were treated with between 0.15 and 0.30 mg/day r-hGH liquid formulation for 39 weeks. The primary endpoint was the proportion of patients who developed BAbs at any time. Secondary endpoints were the proportion of patients with BAbs who became positive for neutralising antibodies, the effects on biomarkers of r-hGH exposure, safety, and adherence to treatment downloaded from the easypod™ connect software. Results Seventy-eight patients (61.5% men) with mean age 44.5 years (range 21–65) started and 68 (87.2%) completed the 39-week treatment period. 82.1% were treatment naïve; all were negative for BAbs to r-hGH at baseline. The median (interquartile range) duration of treatment [273 (267.0–277.0) days] was consistent with patients receiving the required doses, and mean treatment adherence measured using easypod™ connect was 89.3%. The proportion of patients who developed BAbs was 0% (95% confidence interval 0–4.68%) and biomarker profiles were consistent with exposure to r-hGH. 92.3% of patients reported ≥ 1 adverse event during treatment. Most events were mild or moderate and no new safety concerns were detected. Conclusions The low immunogenicity profile of the liquid formulation was consistent with that for the freeze-dried formulation, and no new safety concerns were reported.