Angelman SyndromePhase 1/2ASCEND-ASNCT07181837
A Phase 1/2 Study of the Safety and Efficacy of MVX-220 in Angelman Syndrome
A Phase 1/2 study testing MVX-220 in people with Angelman Syndrome, run by MavriX Bio, LLC at 3 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of MVX-220 gene therapy in children and adults with Angelman syndrome with UBE3A gene deletion, uniparental disomy, or imprinting center defect genotypes. Read more about this study
- Who is it for?
- Ages 4 to 50 years
- Conditions the study is for
- Angelman Syndrome
- What is being tested?
- MVX-220
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesUnited States
- Study dates
- 29 Oct 2025to 31 May 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Abigail Ryan, 617-355-6000, Abigail.Ryan@childrens.harvard.edu
- Recruiting
Rush University Medical Center
Chicago, Illinois, 60612
Milana Milic, 888-352-7874, Milana_Milic@rush.edu
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Alejandra Gonzalez, 310-423-7779, Alejandra.Gonzalez2@cshs.org
About this study
Official title: 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
The purpose of this study is to evaluate the safety and efficacy of MVX-220 gene therapy in children and adults with Angelman syndrome with UBE3A gene deletion, uniparental disomy, or imprinting center defect genotypes.
Read the detailed description
MVX-220 is an investigational gene replacement therapy intended to provide a functional copy of the UBE3A gene to individuals with Angelman syndrome. This study is designed to evaluate the safety, tolerability and efficacy of MVX-220 in participants with Angelman syndrome who have deletion, uniparental disomy, or imprinting center disorder genotypes. The study has 2 primary cohorts: Cohort 1 that includes adults followed by Cohort 2 that includes children. All patients will receive a single dose of MVX-220 administered by injection into the cisterna magna. There is no control group and all individuals will receive the gene therapy. An independent data safety monitoring board will review the safety information from Cohort 1 before individuals can be enrolled in Cohort 2. An optional cohort of adults and/or children (Cohort 3) may be enrolled based on a review of data from Cohorts 1 and 2. All patients will be required to take steroids before and for a brief period during the study to help mitigate the risk of immune response to the gene therapy. Patients will be followed for safety and efficacy for an initial 2-year period post-treatment and then transition to less frequent monitoring schedule for an additional 3 years. The total duration of follow up in the study is 5 years.
- Conditions
- Angelman Syndrome
- Being tested
- MVX-220
- Keywords
- Angelman syndrome, gene therapy, AAV, cisterna magna
- Medical subject headings
- Angelman Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MVX-220Genetic
AAVhu68 viral vector
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Adults ages 18-50 | Experimental | MVX-220, single dose intra cisterna magna injection Receives: Genetic: MVX-220 |
| Cohort 2: Children ages 4-8 | Experimental | MVX-220, single dose intra cisterna magna injection Receives: Genetic: MVX-220 |
| Cohort 3: Optional cohort, adults and children ages 4-50 | Experimental | MVX-220, single dose intra cisterna magna injection Receives: Genetic: MVX-220 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest as assessed through clinical safety, laboratory tests, ECG, vital sign measurements, and physical examinations
Measured: Up to Week 104
Secondary outcomes (11)
Change in communication ability as assessed by the Observer Reported Communication Ability (ORCA) measure
The ORCA measure is a caregiver reporter assessment of communication ability that was developed specifically for Angelman syndrome. The ORCA measure produces a single score that is an estimate of an individual's overall level of communication ability, with higher T-scores reflecting greater communication ability.
Measured: From Baseline to Week 104
Change in developmental milestones as assessed by the Bayley Scale of Infant and Toddler Development, Fourth Edition (Bayley-4)
The Bayley-4 is a performance-based assessment of developmental functioning across communication, cognition, and motor skills. The total raw score reflects the sum of all the item scores within a subdomain, with higher scores reflecting greater ability.
Measured: From Baseline to Week 104
Change in adaptive behaviors as assessed by Vineland Adaptive Behavior Scale (VABS-3)
The VABS-3 assesses adaptive behaviors across multiple domains through a clinician-directed interview of a caregiver of an individual with AS. The total raw score reflects the sum of all the item scores within a subdomain, with higher scores reflecting greater ability.
Measured: From Baseline to Week 104
Change in Symptoms by the Angelman Severity Assessment (ASA)
The ASA is a clinician-reported outcome measure for Angelman syndrome. The clinicians rate their overall impression of the improvement in disease-related symptoms utilizing a 7-point scale, ranging from "very much improved" to "very much worse".
Measured: From Baseline to Week 104
Change in behaviors as assessed by the Aberrant Behavior Checklist-Community (ABC-C)
The ABC-C is a caregiver-rated questionnaire that evaluates key domains in behavior. Items are assessed on a 4 point scale ranging from "not at all a problem" to "the behavior is a severe problem".
Measured: From Baseline to Week 104
Change in ambulatory ability as assessed by the wearable device (Syde®)
The Syde is a wearable device that collects continuous data on the ambulatory ability of participants with AS.
Measured: From Baseline to Week 104
Change in sleep parameters as assessed by a sleep diary
The sleep diary is a caregiver-reported measure of sleep in individuals with AS.
Measured: From Baseline to Week 104
Change in health-related quality of life as assessed by Quality of Life Inventory-Disability (QI-Disability)
The QI-Disability is a caregiver-reported outcome assessment of the health-related quality of life for children and adolescents with intellectual disabilities. Item are rated on a 5-point scale, ranging from "never" to "always ".
Measured: Baseline to Week 104
Change in viral deoxyribonucleic acid (vDNA) levels in CSF and blood
Measured: Baseline to Week 104
Change in viral DNA levels in urine and feces
Measured: From Baseline to Week 104
Change in relevant Electroencephalogram (EEG) parameters (delta power, epileptiform activity)
Measured: From Baselien through Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2025
- Study start29 Oct 2025
- Primary completion31 Mar 2028 (estimated)
- Study completion31 May 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MavriX Bio, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07181837
- Sponsor's protocol ID
- MVX-AAV-101
- Acronym
- ASCEND-AS
- Status last verified
- Jul 2026
- First submitted
- 6 Sep 2025
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07181837
- Acronym / sponsor ID
- ASCEND-AS / MVX-AAV-101
- Conditions
- Angelman Syndrome
- Keywords
- Angelman syndrome, gene therapy, AAV, cisterna magna
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- MavriX Bio, LLCIndustry (pharma, biotech, devices)
- Study start
- 29 Oct 2025 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 May 2031 (estimated)
- First posted
- 18 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and efficacy of MVX-220 gene therapy in children and adults with Angelman syndrome with UBE3A gene deletion, uniparental disomy, or imprinting center defect genotypes.
Detailed description
MVX-220 is an investigational gene replacement therapy intended to provide a functional copy of the UBE3A gene to individuals with Angelman syndrome. This study is designed to evaluate the safety, tolerability and efficacy of MVX-220 in participants with Angelman syndrome who have deletion, uniparental disomy, or imprinting center disorder genotypes. The study has 2 primary cohorts: Cohort 1 that includes adults followed by Cohort 2 that includes children. All patients will receive a single dose of MVX-220 administered by injection into the cisterna magna. There is no control group and all individuals will receive the gene therapy. An independent data safety monitoring board will review the safety information from Cohort 1 before individuals can be enrolled in Cohort 2. An optional cohort of adults and/or children (Cohort 3) may be enrolled based on a review of data from Cohorts 1 and 2. All patients will be required to take steroids before and for a brief period during the study to help mitigate the risk of immune response to the gene therapy. Patients will be followed for safety and efficacy for an initial 2-year period post-treatment and then transition to less frequent monitoring schedule for an additional 3 years. The total duration of follow up in the study is 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Adults ages 18-50 | Experimental | Genetic: MVX-220MVX-220, single dose intra cisterna magna injection |
| Cohort 2: Children ages 4-8 | Experimental | Genetic: MVX-220MVX-220, single dose intra cisterna magna injection |
| Cohort 3: Optional cohort, adults and children ages 4-50 | Experimental | Genetic: MVX-220MVX-220, single dose intra cisterna magna injection |
Who may qualify
- Ages
- 4 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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:
- 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 (21 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MVX-220AAVhu68 viral vector | Genetic | Cohort 1: Adults ages 18-50, Cohort 2: Children ages 4-8, Cohort 3: Optional cohort, adults and children ages 4-50 |
Primary outcome
Incidence of Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest as assessed through clinical safety, laboratory tests, ECG, vital sign measurements, and physical examinations
Time frame: Up to Week 104
11 secondary outcomes
Change in communication ability as assessed by the Observer Reported Communication Ability (ORCA) measure
Time frame: From Baseline to Week 104
Change in developmental milestones as assessed by the Bayley Scale of Infant and Toddler Development, Fourth Edition (Bayley-4)
Time frame: From Baseline to Week 104
Change in adaptive behaviors as assessed by Vineland Adaptive Behavior Scale (VABS-3)
Time frame: From Baseline to Week 104
Change in Symptoms by the Angelman Severity Assessment (ASA)
Time frame: From Baseline to Week 104
Change in behaviors as assessed by the Aberrant Behavior Checklist-Community (ABC-C)
Time frame: From Baseline to Week 104
Change in ambulatory ability as assessed by the wearable device (Syde®)
Time frame: From Baseline to Week 104
Change in sleep parameters as assessed by a sleep diary
Time frame: From Baseline to Week 104
Change in health-related quality of life as assessed by Quality of Life Inventory-Disability (QI-Disability)
Time frame: Baseline to Week 104
Change in viral deoxyribonucleic acid (vDNA) levels in CSF and blood
Time frame: Baseline to Week 104
Change in viral DNA levels in urine and feces
Time frame: From Baseline to Week 104
Change in relevant Electroencephalogram (EEG) parameters (delta power, epileptiform activity)
Time frame: From Baselien through Week 104
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MVX-220 in people with Angelman Syndrome, run by MavriX Bio, LLC at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact MavriX Bio, LLC (978-538-8554, info@mvxbio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest as assessed through clinical safety, laboratory tests, ECG, vital sign measurements, and physical examinations (time frame: Up to Week 104). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.