Overview

This is a two-part, Phase IIa, multicenter, 12-week, open-label study. Up to 56 participants with deletion Angelman Syndrome (AS) aged 5-17 years (inclusive) will be enrolled in the study.

Eligibility

Inclusion Criteria:

• Clinical diagnosis of AS and a genetic subtype of deletion on the maternally inherited chromosome 15q11q13 confirmed by a historical molecular diagnosis. The deletion must include UBE3A, GABRB3, GABRA5, and GABRG3 genes, and be less than 7 Mb in size.
• Body mass index (BMI) below the 97th percentile and above the 3rd percentile for the same age and sex
• 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.
• Female participants:

        A female participant is eligible to participate if she is not pregnant, not breastfeeding,
        and non-childbearing or remain abstinent and/or Hormonal contraceptive methods must be
        supplemented
        -Male participants: Male contraception is not required in this study because of the minimal
        seminal dose transmitted through sexual intercourse
        Exclusion Criteria:
          -  A molecular diagnosis of AS with genotypic classification of any type besides the
             molecular diagnosis as specified in Inclusion Criterion
          -  Concurrent cardiovascular disease considered not well controlled by drug treatment,
             including participants with clinically significant hypertension, bradycardia and
             arrhythmias, myocardial infarction within 12 months of screening or uncompensated
             heart failure
          -  Confirmed clinically significant abnormality on 12-lead ECG, including:
          -  a QTcF of >/= 450 ms (based on the average of 3 consecutive measurements) for
             participants older than 10 years old
          -  a QTcB of >/= 450 ms (based on the average of 3 consecutive measurements) for
             participants up to, and including, the age of 10 years old
          -  Congenital heart diseases not treated and congenital QTc prolongation or family
             history of Long QT Syndrome
          -  Medical history of malignancy if not considered cured or if occurred within the last 5
             years with the exception of fully excised non-melanoma skin cancers or in-situ
             carcinoma of the cervix that has been successfully treated
          -  Concomitant disease, condition, or treatment that would either interfere with the
             conduct of the study or pose an unacceptable risk to the participant in the opinion of
             the Investigator.
          -  Known active or uncontrolled bacterial, viral, or other infection (excluding fungal
             infections of nail beds) or any major episode of infection or hospitalization
             (relating to the completion of the course of antibiotics) within 6 weeks prior to the
             start of drug administration. Rescreening is allowed once the infection is cured and
             if the rescreening criteria are met.
          -  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)
          -  Hospitalization for any major medical or surgical procedure involving general
             anesthesia within 12 weeks of Screening or planned during the study. Rescreening is
             allowed not earlier than 12 weeks after the surgery and if the rescreening criteria
             are met.
          -  Use of prohibited medications within 6 weeks or 5 half-lives (t1/2) prior to start of
             study medication on Day 1 (whichever is longer)
          -  Clinically significant loss of blood within 3 months prior to screening defined by
             participant age and weight per recommendations from Duke University (2012)
          -  Any prior or current treatment with an investigational study drug within 6 weeks or 5
             times the t1/2 of the investigational molecule (whichever is longer) prior to baseline
             or prior or current use of an investigational medical device within 6 weeks prior to
             baseline 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 Investigator.
          -  Previous participation in a cellular therapy, gene therapy, or gene editing clinical
             study
          -  Clinically significant vital sign or ECG abnormalities at Screening
          -  Confirmed clinically significant abnormality in hematological, chemistry or
             coagulation laboratory parameters
          -  Uncorrected hypokalemia or hypomagnesaemia
          -  Positive test result at screening for hepatitis B surface antigen (HBsAg), HCV
             (untreated), or HIV-1/2. Participants with HCV who have been successfully treated and
             who test negative for HCV RNA may be considered eligible for entry into the study.