ontwikkelingsstoornis door een chromosoomdeletie Angelman syndrome developmental disorder
Conditions
Interventions
RO7248824 is a selective synthetic 20-mer oligonucleotide (see RO7248824
Investigator*s Brochure). IT injection of RO7248824 is considered to be a
potential disease modifying approach for AS.
It i
however, administration of two injections 8 weeks apart may be
implemented at a lower dose level than 120 mg based on emerging data.
There is currently no clinical experience with RO7248824. The ev
Sponsors
Roche Nederland B.V.
Eligibility
Age
No minimum to 11 Years
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 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. • Bodyweight of >= 7 kg. • Participant must be >= 1 and
Exclusion criteria
Exclusion criteria: • Clinically-significant laboratory, vital sign or electrocardiography (ECG) abnormalities at Screening. • Molecular diagnosis of AS with genotypic classification of: o UBE3A missense mutation of maternal allele 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, renal disease event or laboratory abnormality, in the judgement of the Investigator. • 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 lumbar puncture 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. • 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 halflife 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, non-drug and non-interventional studies) without a signed data sharing agreement covering the participant in place between other clinical study and the Sponsor. • Previous participation in a cellular therapy, or gene therapy or gene editing, or any other gene expression modulating clinical study. Exclusion Criteria for Optional Open-label Extension Part: 22. The participants re-entering the study to participate in the OOE must continue to comply with exclusion criteria 1 to 21 as stated in the protocol at the time of enrollment in the OOE. a. ECG will be waived for participants who are re-entering the study. 23. Participants who never enrolled in Study BP41674, or who discontinued participation due to safety reasons, are not eligible for the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Frequency and severity of adverse events, serious adverse events, treatment discontinuations due to adverse events. - Frequency of abnormal laboratory findings (blood and cerebrospinal fluid [CSF]). - Frequency of abnormal vital signs and ECG values. - Mean changes from baseline in vital signs (temperature, systolic and diastolic blood pressure, heartrate, respiratory rate) over time. Endpoints measured in OOE part: • Frequency and severity of adverse events, serious adverse events, treatment discontinuations due to adverse events. • Frequency of abnormal laboratory findings (blood and cerebrospinal fluid [CSF]). | — |
Secondary
| Measure | Time frame |
|---|---|
| - Time to maximum concentration (Tmax) - Maximum plasma concentration observed (Cmax) - 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) | — |
Countries
Netherlands
Outcome results
None listed