A Phase 1/2 Study of the Safety and Efficacy of MVX-220 in Angelman Syndrome

Inclusion criteria

• The participant's parent/legal guardian must provide written informed consent.
• Symptoms consistent with AS and documented genetic confirmation of one of the following genotypes resulting in a diagnosis of AS:
• Full maternal UBE3A gene deletion causing AS in the region of 15q11.2-q13
• Uniparental disomy
• Imprinting center defect
• The participant must be 18 to 50 years of age, inclusive (for adult participants), or 4 to 8 years of age, inclusive (for pediatric participants), at Screening.
• The participant must have the ability to ambulate independently.
• The participant must be on stable antiepileptic medications (with no changes within 1 month prior to the Screening visit, except for weight associated dose adjustments). Key

Exclusion criteria

• Clinically significant medical finding other than AS, that, in the judgment of the Investigator would make the participant unsuitable for participation.
• Laboratory abnormalities including but not limited to:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> upper limit of normal (ULN)
• Total and/or fractionated bilirubin (direct and/or indirect) \> ULN
• Gamma-glutamyl transferase (GGT) \> ULN
• Estimated glomerular filtration rate (eGFR) below the lower limit of normal (LLN) for age
• Hemoglobin \< 8 g/dL
• White blood cell (WBC) count outside the normal range for age
• Platelet count \< LLN
• Partial thromboplastin time (PTT) outside the reference range
• PT/International normalized ratio (INR) outside the reference range
• Any known history and/or family history of hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) or multisystem inflammatory syndrome (MIS).
• Any known history and/or family history of disordered complement function and/or complement gene mutation(s).
• History of systemic lupus erythematous, Still's disease, rheumatoid arthritis, and/or other severe autoimmune conditions per judgment of the Investigator.
• Any known history of thrombotic microangiopathy (TMA)/microangiopathic hemolytic anemia, or hypercoagulable conditions including, but not limited to, disseminated intravascular coagulation (DIC), deep venous thrombosis, and pulmonary embolism.
• Current therapy with high dose immunosuppressants.
• Prior or current treatment with an investigational drug within 6 months or 5-half-lives of the hospital admission whichever is longer.
• Prior treatment with an antisense oligonucleotide within 1 year of hospital admission.
• A history of gene therapy administration.
• Any contraindication to ICM administration procedure, including contraindications to imaging, contrast use, anesthesia, or any condition that would increase the risk of adverse outcomes from the ICM procedure.
• Any contraindication to glucocorticoid use