Ensayos clínicos

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 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: 
  • UBE3A truncation mutation of maternal allele;
  • Deletion on the maternally inherited chromosome 15q11q13 that includes the UBE3A gene and is less than 7 Mb in size.
• 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 under study. These provisions are nonetheless included for purposes of completeness in order to make clear that individuals who are pregnant, or are engaging in actions that may cause them to become pregnant, should not participate in this study.
• Consent must be provided by the legal representative for all 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;
  • 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.
  • 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.
• During the treatment period and for at least 6 months after the final dose of RO7248824, consent has to be provided to:
  • 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.

Exclusion Criteria:

• Clinically-significant laboratory, vital sign or electrocardiography (ECG) abnormalities at Screening, including clinically significant abnormalities in:
  • Coagulation: abnormal coagulation profile demonstrated by platelet count at or below lower limit of normal (140 x 10^9 /L) or by abnormal INR, and/or PT, or aPTT;
  • Renal function: estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m^2 (Schwartz and Work 2009).
• Molecular diagnosis of AS with genotypic classification of:
  • Paternal UPD of 15q11-13;
  • UBE3A ID;
  • 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, including:
  • tumors or abnormalities detected by MRI or CT;
  • subarachnoid hemorrhage;
  • clinical suggestion of raised intracranial pressure confirmed on MRI or ophthalmic examination;
  • spinal stenosis or curvature (considered by investigator sufficient to prohibit LP);
  • Chiari malformation;
  • hydrocephalus;
  • syringomyelia;
  • tethered spinal cord syndrome and connective tissue disorders such as EhlersDanlos syndrome and Marfan syndrome.
• 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.
• Concurrent or planned concurrent participation in any clinical study (including observational, non-drug and non-interventional studies) without a signed data sharing agreement in place between the 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.

Eligibility last updated 6/27/22. Questions regarding updates should be directed to the study team contact.