ESPE Abstracts (2019) 92 P1-156

Prospective, Open-Label, Long-Term Follow-Up of Neonates and Young Children with Adrenal Insufficiency Treated with Hydrocortisone Granules

Uta Neumann1, Katarina Braune1, Martin Whitaker2, Susanna Wiegand1, Heiko Krude1, John Porter2, Dena Digweed2, Bernard Voet2, Richard Ross3, Oliver Blankenstein1

1Charité Universitätsmedizin Berlin, Berlin, Germany. 2Diurnal Ltd., Cardiff, United Kingdom. 3University of Sheffield, Sheffield, United Kingdom

Introduction: Children with congenital adrenal hyperplasia (CAH) and adrenal insufficiency (AI) rely on lifelong hormone replacement with hydrocortisone (HC). Alkindi® is the first HC licensed for children from birth to 18 years with AI, available in small doses of 0.5, 1, 2 and 5mg required for the needs of neonates, infants and children.

Objectives: Primary: long-term safety of Alkindi®; Secondary: long-term disease control in children aged 0-6 years.

Methods: Of the 24 patients who completed the initial Phase 3 trial, 18 patients, aged 0-5 years, were enrolled in this long-term study (CAH, n=17; hypopituitarism, n=1). Median ages at entry were 3.6 years in cohort 1 (2- < 6 years in the initial trial, n=9), 2 years in cohort 2 (1 month- < 2 years in the initial trial, n=6) and 46 days in cohort 3 (<28 days in the initial trial, n=3). Ten subjects were male, all were white (Caucasian). Children were observed by two visits every month, followed up by 3 monthly visits thereafter. Therapy was controlled by routinely taken 17-OHP saliva sampling every three months starting from 3-6 months of age.

Results: Children were observed over >2 years (median 795 days (1-872 days)). Six, mainly older children, withdrew their consent due to personal reasons. All other children were compliant with treatment. Hydrocortisone granules (Alkindi®) were prescribed every 8 hours with a mean daily dose per BSA between 10.98 – 12.85 mg/m² in cohort 1, 9.17 – 10.64 mg/m² in cohort 2 and 10.46 – 17.52 mg/m² in cohort 3. All but one patient with panhypopituitarism received additional fludrocortisone therapy.

Safety: No cases of adrenal crisis and no AEs of choking. A total of 193 treatment-emergent adverse events (TEAEs) were reported by 14 subjects (77.8%) with the primary diagnosis being fever and viral upper respiratory tract infection. No deaths, severe TEAEs, TEAEs leading to withdrawal from the study and no TEAEs with a suspected causal relationship to Alkindi®. Nine serious adverse events (SAEs) were reported in three patients (gastroenteritis, vomiting, urinary tract infection, erysipelas), all of them considered not related to Alkindi®.

Efficacy: Standard deviation scores for height and weight showed no trends for accelerated or reduced growth.

Conclusions: During >2-year follow up of children aged 0-7 years, no AEs related to Alkindi® treatment and no adrenal crisis occurred. All children grew along their expected percentiles. Mean daily HC-dose controlled by routine saliva sampling was at the lower recommended dose-range.