FP20-3 SAFETY RESULTS FROM A PHASE II, RANDOMIZED, OPEN-LABEL, ACTIVE-CONTROLLED TRIAL OF RHGH/RHIGF-1 CO-ADMINISTRATION THERAPY IN CHILDREN WITH SHORT STATURE, LOW IGF-1 AND GH SUFFICIENCY

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP20-Growth: Clinical Trials & Observational Studies
Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:55 AM
Room 122 (Moscone Center)

Poster Board SUN-624
Bradley Scott Miller*1, Philippe Ferdinand Backeljauw2, Pascale Dutailly3, Aude Sicsic3, Elizabeth Lawson4, Daniel Esten Hale5, Barry J Reiner6 and Mark A Sperling7
1University of Minnesota Amplatz Children's Hospital, Minneapolis, MN, 2Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 3Ipsen Innovation, Les Ulis, France, 4Ipsen US, Brisbane, CA, 5UT Health Science Center, San Antonio, TX, 6Baltimore, MD, 7Children's Hospital of Pittsburgh, Pittsburgh, PA
Introduction: Growth disorders resulting from defects in the GH–IGF-1 axis form a continuum from GHD to GH resistance, with varying response to rhGH therapy (1,2). In contrast to children with GHD, children with short stature, low IGF-1 concentrations and GH sufficiency may require high doses of rhGH to reach IGF-1 titration targets (3). In these patients, rhGH/rhIGF-1 co-administration may provide a superior growth response vs rhGH alone.

Methods: This randomized, open-label trial in 27 US pediatric endocrinology centers investigated safety and efficacy of treatment with rhGH alone (45µg/kg QD) compared with rhGH/rhIGF-1 co-administration (three co-admin groups: rhGH 45µg/kg QD plus separate injections of rhIGF-1 of 50, 100 or 150µg/kg QD) in treatment-naïve, prepubertal children (baseline height SDS ≤−2, IGF-1 SDS ≤−1 and maximum stimulated GH ≥10ng/mL). A total of 106 patients were randomized: 26 to rhGH alone and 80 to rhGH/rhIGF-1 co-administration.

Results: Safety data were available for the 106 patients (299 patient-years’ exposure). At baseline, overall mean±SD age was 8.8±2.1 years and height SDS was −2.5±0.4. Treatment emergent adverse events (TEAEs) of special interest included headache (rhGH: 54% vs co-admin: 61%), vomiting (35% vs 29%), otitis media (15% vs 21%), hypoglycemia (8% vs 9%), lipohypertrophy (0% vs 20%) and intracranial hypertension/papilledema (0% vs 3%). The most common TEAEs, in addition to headache, were upper respiratory tract infection (39% vs 40%) and pyrexia (35% vs 40%). Two single cases of serious TEAEs were reported: papilledema (150µg/kg co-admin group) and intracranial hypertension (100µg/kg co-admin group). Both events resolved after discontinuation of treatment and therapy was restarted thereafter. Treatment effects were not evident for C-peptide or fasting venous glucose. Mean glycosylated hemoglobin did not change significantly. At each rhIGF-1 dose, co-admin therapy resulted in greater first-year height velocity vs rhGH alone; rhGH mean±SD: 9.3±1.7cm/year vs co-admin 50, 100 and 150µg/kg dose groups: 10.1±1.3, 9.7±2.5 and 11.2±2.1cm/year, respectively (modified Intention-to-Treat population [n=105]; p<0.001, rhGH alone vs co-admin 150µg/kg).

Conclusion: Additional safety concerns were not evident with co-administration of rhGH/rhIGF-1 therapy in this trial compared with previously reported rhGH and rhIGF-1 safety profiles. rhGH/rhIGF-1 therapy resulted in a first-year height velocity exceeding that of rhGH alone.

(1) Cohen P, et al., J Clin Endocrinol Metab 2007; 92:2480–2486. (2) Savage MO, et al., Clin Endocrinol 2010; 72:721–728. (3) Bang P, et al., Clin Endocrinol 2012; 77:169–181.

Disclosure: BSM: Consultant, Ipsen, Consultant, Genentech, Inc., Consultant, Pfizer, Inc., Consultant, Novo Nordisk, Consultant, Eli Lilly & Company, Consultant, Sandoz, Consultant, Teva, Consultant, Endo Pharmaceuticals, Researcher, Ipsen, Researcher, Genentech, Inc., Researcher, Pfizer, Inc., Researcher, Novo Nordisk, Researcher, Eli Lilly & Company, Researcher, Endo Pharmaceuticals, Researcher, Abbott Laboratories. PFB: Investigator, Ipsen, Member of advisory committees or review panels, Ipsen. PD: Employee, Ipsen. AS: Independent Contractor (including contracted research), Ipsen. EL: Employee, Ipsen. BJR: Principal Investigator, Ipsen, Independent Contractor (including contracted research), Ipsen. Nothing to Disclose: DEH, MAS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The MS316 study was supported by Ipsen