Angelman syndrome is a complex genetic disorder that primarily affects the nervous system.

Phase 1

• Conditions: Angelman Syndrome; MedDRA version: 20.0Level: PTClassification code 10049004Term: Angelman's syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2019-003787-48-NL
• Lead Sponsor: F. Hoffmann-La Roche

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-08
• Last Update Posted: 13 October 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

•The participant has a parent, caregiver or legal representative (hereinafter caregiver”) who is reliable, competent and at least 18 years of age. The caregiver is willing and able to accompany the participant to clinic visits and to be available to the Investigational Site by phone or email if needed and who (in the opinion of the investigator) is and will remain sufficiently knowledgeable of participant’s ongoing condition to respond to any inquiries about the participant from personnel from the Study Site.
•A caregiver must be able to consent for the participant according to International Council on Harmonisation (ICH) and local regulations.
•Ability to comply with all study requirements.
•Have adequate supportive psychosocial circumstances.
•Able to undergo MRI scans (e.g., no metal implants including MRI incompatible intrauterine devices (IUDs), or any condition that renders testing intolerable for the participant), under sedation or anesthesia if needed and as determined appropriate by the Investigator.
•Able to tolerate blood draws.
•Able to undergo LP and IT injection, under sedation or anesthesia if needed and as determined appropriate by the Investigator.
•Stable medical status for at least 4 weeks prior to Screening and at the time of enrollment.
•Participant must be ? 1 to ? 12 years of age at the time of signing of the informed
consent by the caregiver.
•Clinical diagnosis of AS confirmed by a molecular diagnosis with genotypic classification of either:
oUBE3A truncation mutation of maternal allele
o15q11-15 deletion of maternal allele
•Female Participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Women of non-childbearing potential or Women of childbearing potential who agree to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 6 months after the final dose of RO7248824
•Male Participants: During the treatment period and for at least 6 months after the final dose of RO7248824, consent has to be provided to remain abstinent

Are the trial subjects under 18? yes
Number of subjects for this age range: 66
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Clinically-significant laboratory, vital sign or electrocardiography (ECG) abnormalities at Screening.
•Molecular diagnosis of AS with genotypic classification of:
oUBE3A missense mutation of maternal allele
oPaternal UPD of 15q11-13
oUBE3A ID
oA partial molecular diagnosis of AS that cannot exclude UPD or ID despite appropriate genetic testing.
•Clinically relevant hematological, hepatic, cardiac or renal disease or event, in the judgement of the investigator. Pre-existing abnormal hepatic, renal or hematology lab tests must be discussed with the Sponsor Medical Monitor.
•Any concomitant condition that might interfere with the clinical evaluation of AS and that is not related to AS.
•Known history of human immunodeficiency virus (HIV) or hepatitis C.
•Any condition that increases risk of meningitis.
•History of bleeding diathesis or coagulopathy.
•A medical history of brain or spinal disease that would interfere with the LP process, CSF circulation or safety assessment.
•History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch.
•Malignancy within 5 years of Screening.
•Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.
•Have any other conditions which, in the opinion of the Investigator, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study, including any contraindication to administration of intrathecal therapy.
•Premature birth with gestational age at birth below 34 weeks.
•Concurrent or planned concurrent participation in any clinical study (including observational and non-interventional studies) without approval of the Sponsor Medical Monitor. At the discretion of the Sponsor, participants may enroll into non-drug observational studies.
•Previous participation in a gene therapy or gene editing clinical study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified