Angelman Syndrome MedDRA version: 20.0 Level: PT Classification code 10049004 Term: Angelman's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: RO7248824/F02-01
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available
Current Sponsor code: RO7248824
Other descriptive name: RO7248824
Concentration unit: mg/m
Sponsors
F. Hoffmann-La Roche
Eligibility
Sex/Gender
All
Inclusion criteria
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 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. • Bodyweight of = 7 kg. • Participant must be = 1 to = 12 years ears 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: o UBE3A mutation of maternal allele o Deletion on the maternally inherited chromosome 15q11q13 that includes the UBE3A gene and is less than 7 Mb in size. • 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
Exclusion criteria: • Clinically-significant laboratory, vital sign or electrocardiography (ECG) abnormalities at Screening. • Molecular diagnosis of AS with genotypic classification of: o Paternal UPD of 15q11-13 o UBE3A ID o A 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 B virus (HBV) or hepatitis C virus (HCV) • 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 clinically significant 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. • History of hypersensitivity to the investigational medicinal product (IMP), antisense oligonucleotides, or any excipients. •Allowed sleep medications have not been stable for 4 weeks prior to screening and at the time of enrollment. •Allowed medications for treatment of epilepsy have not been stable for 12 weeks prior to screening and at the time of enrollment. • Use of antiplatelet or anticoagulant therapy for 2 weeks prior to screening and at the time of enrollment. • Concurrent psychotropic medications have not been stable for 4 weeks prior to screening and at the time of enrollment. • Received an investigational drug within 90 days or 5 times the half-life of the investigational drug (whichever is longer) or participation in a study testing an investigational medical device within 90 days prior to first dosing or if the device is still active. • 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 cellular therapy, or gene therapy or gene editing clinical study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability profile of RO7248824;Secondary Objective: To investigate the plasma pharmacokinetics (PK) of RO7248824;Primary end point(s): 1. Frequency and severity of adverse events, serious adverse events, treatment discontinuations due to adverse events. 2. Frequency of abnormal laboratory findings (blood and cerebrospinal fluid [CSF]). 3. Frequency of abnormal vital signs and ECG values. 4. Mean changes from baseline in vital signs (temperature, systolic and diastolic blood pressure, heartrate, respiratory rate) over time. ;Timepoint(s) of evaluation of this end point: 1-4. Up to Day 365 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to maximum concentration (Tmax) 2. Maximum plasma concentration observed (Cmax) 3. AUC from Time 0 to time of last sampling point or last quantifiable sample, whichever comes first (AUClast), AUC from Time 0 to infinity (AUCinf) ;Timepoint(s) of evaluation of this end point: 1-3. Up to Day 365 | — |
Countries
Canada, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed