Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: A randomized dose-escalation trial

Tadej Battelino, Michael Højby Rasmussen, Jean De Schepper, Nehama Zuckerman-Levin, Zoran Gucev, Lars Sävendahl, NN8640-4042 Study Group

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

OBJECTIVE: To evaluate the safety, local tolerability, pharmacodynamics and pharmacokinetics of escalating single doses of once-weekly somapacitan, a reversible, albumin-binding GH derivative, vs once-daily GH in children with GH deficiency (GHD).

DESIGN: Phase 1, randomized, open-label, active-controlled, dose-escalation trial (NCT01973244).

PATIENTS: Thirty-two prepubertal GH-treated children with GHD were sequentially randomized 3:1 within each of four cohorts to a single dose of somapacitan (0.02, 0.04, 0.08 and 0.16 mg/kg; n=6 each), or once-daily Norditropin(®) SimpleXx(®) (0.03 mg/kg; n=2 each) for 7 days.

MEASUREMENTS: Pharmacokinetic and pharmacodynamic profiles were assessed.

RESULTS: Adverse events were all mild, and there were no apparent treatment-dependent patterns in type or frequency. Four mild transient injection site reactions were reported in three of 24 children treated with somapacitan. No antisomapacitan/anti-human growth hormone (hGH) antibodies were detected. Mean serum concentrations of somapacitan increased in a dose-dependent but nonlinear manner: maximum concentration ranged from 21.8 ng/mL (0.02 mg/kg dose) to 458.4 ng/mL (0.16 mg/kg dose). IGF-I and IGFBP-3, and change from baseline in IGF-I standard deviation score (SDS) and IGFBP-3 SDS, increased dose dependently; greatest changes in SDS values were seen for 0.16 mg/kg. IGF-I SDS values were between -2 and +2 SDS, except for peak IGF-I SDS with 0.08 mg/kg somapacitan. Postdosing, IGF-I SDS remained above baseline levels for at least 1 week.

CONCLUSIONS: Single doses of once-weekly somapacitan (0.02-0.16 mg/kg) were well tolerated in children with GHD, with IGF-I profiles supporting a once-weekly treatment profile. No clinically significant safety/tolerability signals or immunogenicity concerns were identified.

Original languageEnglish
Pages (from-to)350-358
Number of pages9
JournalClinical Endocrinology
Volume87
Issue number4
DOIs
Publication statusPublished - Oct 2017

Keywords

  • growth hormone
  • growth hormone deficiency
  • IGF-I
  • long-acting growth hormone

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