MVX-220 gene therapy for Angelman syndrome

A Multi-Center, Open-label, Phase 1/2 Trial of the Safety and Efficacy of MVX-220 Gene Therapy Administered by Intra-Cisterna Magna Injection to Participants With Angelman Syndrome

This study will try a single dose of MVX-220 gene therapy injected into the cisterna magna for children and adults with Angelman syndrome caused by UBE3A deletion, uniparental disomy, or imprinting center defects.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 4 Years to 50 Years
• Sex: All
• Sponsor: MavriX Bio, LLC (industry)
• Locations: 3 sites (Los Angeles, California and 2 other locations)
• Trial ID: NCT07181837 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 trial gives a single intracisternal dose of MVX-220, an AAV-based UBE3A gene replacement, to cohorts of adults followed by children with confirmed deletion, uniparental disomy, or imprinting center defects. There is no control group; all participants receive the gene therapy and an independent data safety monitoring board reviews adult safety before pediatric enrollment. Participants receive short-course steroids to reduce immune reactions and must be ambulatory and on stable antiepileptic medication at enrollment. Safety and effectiveness are monitored closely for two years after dosing and then with less frequent visits for a total five-year follow-up.

Who should consider this trial

Good fit: Ideal candidates are ambulatory children aged 4–8 or adults aged 18–50 with genetically confirmed Angelman syndrome due to maternal UBE3A deletion, uniparental disomy, or an imprinting center defect who are on stable antiepileptic therapy.

Not a fit: Patients with other AS genotypes (such as point mutations), significant unrelated medical problems, non-ambulatory status, or who fall outside the specified age ranges are unlikely to be eligible or to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, MVX-220 could restore functional UBE3A protein and lead to meaningful improvements in development, behavior, and seizure control for people with Angelman syndrome.

How similar studies have performed: AAV-based gene replacement targeting UBE3A has shown promising results in animal models and AAV CNS gene therapies have demonstrated benefit in other pediatric neurogenetic disorders, but human data for UBE3A replacement remain very limited.

Eligibility criteria

Key Inclusion Criteria:

1. The participant's parent/legal guardian must provide written informed consent.
2. Symptoms consistent with AS and documented genetic confirmation of one of the following genotypes resulting in a diagnosis of AS:

   1. Full maternal UBE3A gene deletion causing AS in the region of 15q11.2-q13
   2. Uniparental disomy
   3. Imprinting center defect
3. 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.
4. The participant must have the ability to ambulate independently.
5. 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:

1. Clinically significant medical finding other than AS, that, in the judgment of the Investigator would make the participant unsuitable for participation.
2. Laboratory abnormalities including but not limited to:

   1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> upper limit of normal (ULN)
   2. Total and/or fractionated bilirubin (direct and/or indirect) \> ULN
   3. Gamma-glutamyl transferase (GGT) \> ULN
   4. Estimated glomerular filtration rate (eGFR) below the lower limit of normal (LLN) for age
   5. Hemoglobin \< 8 g/dL
   6. White blood cell (WBC) count outside the normal range for age
   7. Platelet count \< LLN
   8. Partial thromboplastin time (PTT) outside the reference range
   9. PT/International normalized ratio (INR) outside the reference range
3. Any known history and/or family history of hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) or multisystem inflammatory syndrome (MIS).
4. Any known history and/or family history of disordered complement function and/or complement gene mutation(s).
5. History of systemic lupus erythematous, Still's disease, rheumatoid arthritis, and/or other severe autoimmune conditions per judgment of the Investigator.
6. 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.
7. Current therapy with high dose immunosuppressants.
8. Prior or current treatment with an investigational drug within 6 months or 5-half-lives of the hospital admission whichever is longer.
9. Prior treatment with an antisense oligonucleotide within 1 year of hospital admission.
10. A history of gene therapy administration.
11. 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.
12. Any contraindication to glucocorticoid use

Where this trial is running

Los Angeles, California and 2 other locations

• Cedars-Sinai Medical Center — Los Angeles, California, United States (RECRUITING)
• Rush University Medical Center — Chicago, Illinois, United States (RECRUITING)
• Boston Children's Hospital — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Study coordinator: MavriX Bio, LLC

Conditions: Angelman Syndrome, Angelman syndrome, gene therapy, AAV, cisterna magna