For Healthcare Professionals

A Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of RO7248824 In Participants With Angelman Syndrome


About the study

This is a Phase I, multicenter, non-randomized, adaptive, open label, multiple ascending, intra-participant, dose-escalation study with an LTE part. The objective of the study is to investigate the safety, tolerability, PK and PD of RO7248824 in participants administered IT 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 A4 (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-A4 preceding and gating the linked cohort B1-B5 (e.g., A1 precedes B1).

Who can take part

You may be eligible to participate in the study if you meet the following criteria:


  1. 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.
  2. A caregiver must be able to consent for the participant according to International Council on Harmonisation (ICH) and local regulations.
  3. Ability to comply with all study requirements.
  4. Have adequate supportive psychosocial circumstances.
  5. Able to tolerate blood draws.
  6. Able to undergo LP and IT injection, under sedation or anesthesia if needed and as determined appropriate by the Investigator.
  7. Stable medical status for at least 4 weeks prior to Screening and at the time of enrollment.
  8. Body weight of ≥ 7 kg
  9. Participant must be ≥ 1 to ≤ 12 years of age at the time of signing of the informed consent by the caregiver.
  10. Clinical diagnosis of AS confirmed by a molecular diagnosis with genotypic classification of either UBE3A mutation of the maternal allele or deletion on the maternally inherited chromosome 15q11q13 that includes the UBE3A gene and is less than 7 Mb in size. Reproductive Status: Some of the provisions that follow may have limited applicability based on the age range of study participants (i.e., up to the age of 12) and the nature of the disease understudy. These provisions are nonetheless included for purposes of completeness in order: 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:
  11. Women of non-childbearing potential.
  12. 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 (RG6091). The following are acceptable contraceptive methods: bilateral tubal occlusion/ ligation, male sexual partner who is sterilized, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices, male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide. Male Participants During the treatment period and for at least 6 months after the final dose of RO7248824 (RG6091), consent has to be provided to:
  13. Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom, with a female partner of childbearing potential, or pregnant female partner, to avoid exposing the embryo. The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure.


Diagnostic Assessments

  1. Clinically-significant laboratory, vital sign or electrocardiography (ECG) abnormalities at Screening Type of Participants and Disease Characteristics
  2. Molecular diagnosis of AS with genotypic classification: UBE3A missense mutation of maternal allele Paternal Uniparental Disomy (UPD) of 15q11-13 UBE3A Imprinting center defect (ID) A partial molecular diagnosis of AS, that cannot exclude UPD or ID despite appropriate genetic testing. Medical history and concurrent disease
  3. 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.
  4. Any concomitant condition that might interfere with the clinical evaluation of AS and that is not related to AS.
  5. Known history of human immunodeficiency virus (HIV) or hepatitis B virus (HBV) or hepatitis C virus (HCV).
  6. Any condition that increases risk of meningitis.
  7. History of bleeding diathesis or coagulopathy.
  8. A medical history of brain or spinal disease that would interfere with the LP process, cerebrospinal fluid (CSF) circulation or safety assessment
  9. History of clinically significant post-lumbar-puncture headache of moderate or severe intensity and/or blood patch
  10. Malignancy within 5 years of Screening
  11. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study
  12. 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.
  13. Premature birth with gestational age at birth below 34 weeks.
  14. History of hypersensitivity to the investigational medicinal product (IMP), antisense oligonucleotides, or any excipients. Prior Therapy
  15. Allowed sleep medications have not been stable for 4 weeks prior to screening and at the time of enrollement.
  16. Allowed medications for treatment of epilepsy have not been stable for 12 weeks prior to screening and at the time of enrollment.
  17. Use of antiplatelet or anticoagulant therapy for 2 weeks prior to screening and at the time of enrollment.
  18. Concurrent psychotropic medications have not been stable for 4 weeks prior to screening and at the time of enrollment. Other
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Study Locations

Enter your ZIP code/Postal code/PIN code to locate study sites near you:

How to Apply

Contact the study center to learn if this study is a good match for you.
Phone iconCall 888-662-6728 (U.S. and Canada)Email iconEmail Study Center

Study’s details


Angelman Syndrome

Age (in years)

1 - 12


Phase 1

Participants needed


Est. Completion Date

Aug 2024

Treatment type



Hoffmann-La Roche identifier


Study number


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