ESPE2023 Free Communications Fetal, neonatal endocrinology and metabolism (to include hypoglycaemia) & Multisystem endocrine disorders (6 abstracts)
Dasiglucagon safety in paediatric participants with CHI
Thomas Meissner 1 , Diva D. De León 2 , Paul Thornton 3 , David Zangen 4 , Klaus Mohnike 5 , Marie Andersen 6 , Eva Bøge 6 , Sune Birch 6 , Jelena Ivkovic 6 & Indi Banerjee 7
1Department of General Paediatrics, Neonatology and Paediatric Cardiology, Medical Faculty, University Children's Hospital Düsseldorf, Düsseldorf, Germany. 2Congenital Hyperinsulinism Center, Department of Pediatrics, The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA. 3Congenital Hyperinsulinism Center, Cook Children’s Medical Center, Fort Worth, USA. 4Division of Pediatric Endocrinology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. 5Department of Pediatrics, Children’s Hospital, Otto-von-Guericke-University, Magdeburg, Germany. 6Zealand Pharma A/S, Søborg, Denmark. 7Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, United Kingdom
Background: Congenital hyperinsulinism (CHI) is a rare disorder, which causes persistent and severe hypoglycaemia in infants and children. CHI can be treated with glucagon, but long-term use is challenging owing to its instability in aqueous solution. Dasiglucagon, a stable glucagon analogue designed for long-term use as a subcutaneous continuous infusion, is in clinical development. Here, we present dasiglucagon safety results in participants treated for up to 8 weeks from 2 completed trials.
Methods: Trial 17103 (NCT04172441) included neonates and infants with CHI aged 7–364 days. In Part 1 (P1), participants were randomized to receive dasiglucagon or placebo (48 hours each) in a double-blind, crossover design. In open-label Part 2 (P2), all participants received dasiglucagon for 21 days. Open-label trial 17109 (NCT03777176) included children with CHI aged 3 months to 12 years. In P1 participants were randomized to receive standard of care (SOC) or dasiglucagon+SOC for 4 weeks. In P2 all participants received dasiglucagon+SOC for 4 weeks. Safety analysis comprised treated participants.
Results: In trials 17103 (n=12) and 17109 (n=32) respectively, participants’ median age was 1.3 months and 4.3 years; 83.3% and 50.0% were male. Most participants had not had a pancreatectomy (17103: 91.7%; 17109: 65.6%). The table summarizes safety results. In both trials, most treatment-emergent adverse events (TEAEs) were mild. Hemodynamic events were infrequent; no clinically relevant abnormalities were observed for blood pressure and heart rate. Necrolytic migratory erythema (NME) was confirmed in 2 participants.
| 17103 (n=12) | 17109 (n=32) | |
| Participants completing trial, n (%) | 12 (100.0) | 32 (100.0) |
| Participants with TEAEs, n (%) | ||
| P1 | Dasiglucagon (n=12): 3 (25.0) Placebo (n=12): 7 (58.3) | Dasiglucagon+SOC (n=16): 14 (87.5) SOC (n=16): 8 (50.0) |
| P2 | 10 (83.3) | 24 (75.0) |
| Most common TEAEs, n (%) | ||
| Vomiting | 3 (25.0) | 7 (21.9) |
| Eczema | 0 | 6 (18.9) |
| Papular rash | 3 (25.0) | 0 |
| Anaemia | 3 (25.0) | 0 |
| Serious TEAEs, n (%) | ||
| P1 | 0 | Dasiglucagon+SOC (n=16): 2 (12.5)b SOC (n=16): 1 (6.3)c |
| P2 | 1 (8.3)a | 2 (6.3)d |
| Discontinuation due to TEAEs, n (%) | ||
| P1 | 0 | 0 |
| P2 | 0 | 1 (3.1)e |
| NME, n (%) | ||
| P1 | 0 | 0 |
| P2 | 0 | 2 (6.3) |
| aAcute respiratory failure; bvascular device infection, localised infection; chypoglycemia; dfolliculitis, H1N1 influenza, hyperglycemia; ehyperglycemia | ||
Conclusions: Dasiglucagon was well tolerated over 8 weeks, with a good and expected safety profile, confirming known class effects; no new safety concerns were identified. A trial investigating dasiglucagon’s long-term safety profile is ongoing.
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