nnc0195-0092 and Growth-Disorders

Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD).. Evaluate the efficacy and tolerability of somapacitan in children with GHD after 2 years of treatment and after the switch from daily GH.. A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising a 52-week main phase and 3-year safety extension (NCT03811535).. Eighty-five sites across 20 countries.. A total of 200 treatment-naïve prepubertal patients were randomized and exposed; 194 completed the 2-year period.. Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (0.034 mg/kg/d) during the first year, after which all patients received somapacitan 0.16 mg/kg/wk.. Height velocity (HV; cm/year) at week 104. Additional assessments included HV SD score (SDS), height SDS, IGF-I SDS, and observer-reported outcomes.. HV was sustained in both groups between 52 and 104 weeks. At week 104, mean (SD) for HV between weeks 52 and 104 was 8.4 (1.5) cm/year after continuous somapacitan treatment and 8.7 (1.8) cm/year after 1 year of somapacitan treatment following switch from daily GH. Secondary height-related endpoints also supported sustained growth. Mean IGF-I SDS during year 2 was similar between groups and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or tolerability issues identified. GH patient preference questionnaire results show that most patients and their caregivers (90%) who switched treatment at year 2 preferred once-weekly somapacitan over daily GH treatment.. Somapacitan in children with GHD showed sustained efficacy and tolerability for 2 years, and after switching from daily GH. Patients/caregivers switching from daily GH expressed a preference for somapacitan.. NCT03811535.

Topics: Body Height; Child; Dwarfism, Pituitary; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I

Human growth hormone (hGH) replacement therapy currently requires daily sc injections for years/lifetime, which may be both inconvenient and distressing for patients. NNC0195-0092 is a novel hGH derivative intended for once-weekly treatment of GH deficiency. A noncovalent albumin binding moiety is attached to the hGH backbone. Clearance is reduced as a consequence of a reversible binding to circulating serum albumin, which prolongs the pharmacodynamic (PD) effect.. To evaluate safety, local tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose (SD) and multiple doses (MD) of NNC0195-0092.. Randomized, single-center, placebo-controlled, double-blind, SD/MD, dose-escalation trial of 105 healthy male subjects. NNC0195-0092 sc administration: Five cohorts of eight subjects received one dose of NNC0195-0092 (0.01-0.32 mg/kg) (n = 6) or placebo (n = 2). Sixteen subjects (equal numbers of Japanese and non-Asian) received once-weekly doses of NNC0195-0092 (0.02-0.24 mg/kg; n=12) or placebo (n=4) for 4 weeks. Blood samples were drawn for assessment of safety, PK, IGF-1, and IGF binding protein 3 profiles and anti-drug antibodies.. SD and MD of NNC0195-0092 were well tolerated at all dose levels. No safety concerns or local tolerability issues were identified. A dose-dependent IGF-1 response was observed. IGF-1 profiles suggest that NNC0195-0092 may be suitable for once-weekly dosing, with a clinically relevant dose ≤0.08 mg/kg/week. No differences in PK and PD were observed between Japanese and non-Asian subjects.. SD and MD of NNC0195-0092 administered to healthy Japanese and non-Asian male subjects were well tolerated at all doses. The present trial suggests that NNC0195-0092 has the potential for an efficacious, well-tolerated, once-weekly GH treatment.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Growth Disorders; Human Growth Hormone; Humans; Injections, Subcutaneous; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Lipopeptides; Male; Middle Aged; Placebos; Serum Albumin; Young Adult

Somapacitan is a long-acting growth hormone (GH) in development for once-weekly treatment of GH deficiency (GHD). Optimal monitoring of insulin-like growth factor-I (IGF-I) levels must account for weekly IGF-I fluctuations following somapacitan administration.. To develop and assess the reliability of linear models for predicting mean and peak IGF-I levels from samples taken on different days after dosing.. A pharmacokinetic/pharmacodynamic model was used to simulate IGF-I data in adults and children following weekly somapacitan treatment of GHD.. 39 200 IGF-I profiles were simulated with reference to data from 26 adults and 23 children with GHD.. The simulated dose range was 0.02 to 0.12 mg/kg for adults and 0.02 to 0.16 mg/kg for children. Simulated data with >4 average standard deviation score were excluded.. Linear models for predicting mean and peak IGF-I levels based on IGF-I samples from different days after somapacitan dose.. Robust linear relationships were found between IGF-I sampled on any day after somapacitan dose and the weekly mean (R2 > 0.94) and peak (R2 > 0.84). Prediction uncertainties were generally low when predicting mean from samples taken on any day (residual standard deviation [RSD] ≤ 0.36) and peak from samples taken on day 1 to 4 (RSD ≤ 0.34). IGF-I monitoring on day 4 and day 2 after dose provided the most accurate estimate of IGF-I mean (RSD < 0.2) and peak (RSD < 0.1), respectively.. Linear models provided a simple and reliable tool to aid optimal monitoring of IGF-I by predicting mean and peak IGF-I levels based on an IGF-I sample following dosing of somapacitan. A short visual summary of our work is available (1).

Topics: Adult; Child; Clinical Trials, Phase I as Topic; Drug Administration Schedule; Drug Monitoring; Follow-Up Studies; Growth Disorders; Histidine; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Mannitol; Phenol; Prognosis; Randomized Controlled Trials as Topic; Retrospective Studies; Tissue Distribution