Two-Year Data from a Long-Term Phase IV Study of Recombinant Human Growth Hormone in Short Children Born Small for Gestational Age

Abstract

IntroductionThis ongoing, prospective, open-label, non-comparative, multicenter phase IV study is evaluating the safety and efficacy of recombinant human growth hormone (rhGH; Omnitrope®, Sandoz GmbH) in short children born small for gestational age (SGA). Here we report data from patients who have completed 2 years’ treatment.MethodsEligibility criteria included prepubertal children born SGA with growth disturbances defined as current height standard deviation score (HSDS) <−2.5 and parental adjusted SDS <−1; birth weight and/or length <−2 SDS; and failure of catch-up growth [height velocity (HV) SDS <0 during the last year] by 4 years of age or later. The primary study objective is to assess the long-term effect of Omnitrope treatment on the development of diabetes in short children born SGA. Secondary objectives include evaluation of efficacy, incidence and severity of adverse events (AEs), occurrence of malignancies during treatment, and detection of anti-rhGH antibodies during treatment.ResultsIn total, 278 children have been enrolled and received study medication; 249 have completed 2 years of treatment. No child has developed diabetes mellitus during the first 2 years; no fasting glucose or 2-h oral glucose tolerance test value exceeded the pre-defined limits of >126 or >200 mg/dL, respectively. No adverse alterations in body mass were noted. Treatment-emergent AEs were experienced by 211 (76.2%) children; most of these were of mild-to-moderate intensity (99.3%) and considered unrelated to study medication (97.6%). Treatment with Omnitrope was effective; mean HSDS was −3.39 at baseline, −2.57 at 1 year and −2.15 at 2 years of treatment. Mean HVSDS (peak-centered) also improved, from −2.13 at baseline to +4.16 at 1 year and +2.23 at 2 years.ConclusionIn this second interim analysis, short children born SGA were safely and effectively treated with rhGH (Omnitrope), and 2 years’ treatment had no major adverse impact on carbohydrate metabolism or body mass.FundingSandoz.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0301-1) contains supplementary material, which is available to authorized users.

What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature

“…However, the compensatory increase in AIR was found to be insufficient, resulting in a reduction in the DI, although not leading to T2D [105]. Increases in glucose and insulin levels during GH treatment were reported in studies of up to 3 years' duration [102,104,106]. Fasting insulin and glucose levels increased significantly during 6 years' GH treatment but were not significantly different from baseline, 6 months after stopping GH; at 6.5 years after stopping GH, they were higher than baseline, but similar to untreated SGA controls [107].…”

Ten years of clinical experience with biosimilar human growth hormone: a review of safety data

“…Twenty-four drug-related AEs occurred in 17 (6.1%) patients (hypothyroidism, n=7; headache, n=3; impaired fasting plasma glucose, n=3; IGF-I/IGFBP-3 increased, n=2; thyroid-stimulating hormone increased, n=1; puncture site hematoma, n=1; scoliosis, n=1; upper respiratory tract infection, n=1; bronchitis, n=1; impaired glucose tolerance, n=1; pharyngitis, n=1; viral infection, n=1; scarlet fever, n=1). All were considered mild in severity, except one case of headache, and none required permanent discontinuation of study medication 13. Serious AEs were reported in 22 patients (7.9%), with only one (severe headache) suspected to be related to study treatment.…”

“…This is the largest prospective clinical study so far conducted on rhGH in SGA patients. In total, 278 children have been enrolled and received study medication; 249 have completed 2 years of treatment 13. No child has developed diabetes mellitus during the first 2 years; no fasting glucose or 2-hour oral glucose tolerance test value exceeded the pre-defined limits (>126 or >200 mg/dL, respectively).…”

“…In the phase IV SGA study, anti-rhGH antibody levels above the cutoff value were measured in 7 patients (2.7%) at year 1 and in 3 patients (1.2%) at year 2 13. Positive test results were transient, with only 2 (0.8%) patients having antibodies above the cutoff value on two separate visits.…”

Ten years&#39; clinical experience with biosimilar human growth hormone: a review of efficacy data

“…This Phase IV study began in 2007 and has enrolled 278 children, with 249 children completing 2 years of treatment 12. Treatment with biosimilar rhGH was effective; mean HSDS was −3.39 at baseline, −2.57 at 1 year, and −2.15 at 2 years of treatment.…”