A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7248824 in Participants With Angelman Syndrome (AS)

Summary

This is a phase I, multicenter, non-randomized, adaptive, open-label, multiple ascending, intra-participant, dose-escalation study with a long-term extension (LTE) part and an optional open-label extension (OOE) part. The objective of the study is to investigate the safety, tolerability, PK and PD of RO7248824 administered intrathecally (IT) in participants with AS. Two linked sets of dose escalation cohorts are planned based on two different age groups, namely participants with AS aged ≥ 5 to ≤ 12 years in cohorts A1 to A5 (with at least 2 participants ≤ 8 years old in each cohort) and AS participants aged ≥ 1 to ≤ 4 years in cohorts B1 to B5. The two sets of cohorts will be run in parallel, with each cohort A1 to A5 preceding and gating the linked cohort B1 to B5 (e.g., A1 precedes B1).

Timeline

Start

2020-08-19

Primary completion

2025-07-31

Completion

2025-07-31

Outcome

Met primary endpoint

paper The primary endpoint was met; rugonersen had an acceptable safety and tolerability profile. PMID 40646322 ↗

Publications

• Hipp JF, Bacino CA, Bird LM, Bruenig-Traebert I, Chan D, de Wit MC, Fontoura P, Hooper G, Jagasia R, Krishnan ML, Murtagh L, Noci A, Martinez AR, Schwab D, Serrano M, Shen MD, Tillmann J, Tjeertes J, Vincenzi B, Berry-Kravis E, Bonni A; Rugonersen Study Group; all TANGELO investigators. The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a phase 1 trial. Nat Med. 2025 Sep;31(9):2936-2945. doi: 10.1038/s41591-025-03784-7. Epub 2025 Jul 11.

Drugs

Indications