Phase 1/2 Study of MZ-1866, an AAV-9 Gene Therapy Delivered by Intracerebroventricular Injection to Participants With Pitt Hopkins Syndrome

Mahzi Therapeutics

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Pitt Hopkins Syndrome

Treatments: Genetic: MZ-1866

Study type: Interventional

Funder types: Industry

Identifiers

NCT07135050

MZ1866-CL101

Details and patient eligibility

About

The goal of this clinical trial is to learn if MZ-1866 is a safe and tolerable treatment for children and adults with Pitt Hopkins Syndrome.

To evaluate the safety of MZ-1866, the following will be evaluated:

• frequency and severity of adverse events
• physical exam, laboratory results and electrocardiogram findings

Participants will:

• receive a single dose of MZ-1866 by intracerebroventricular injection
• be seen by the study physician and site staff periodically to assess changes to their health status
• be periodically evaluated using neurodevelopmental tools

Caregivers will:

• be interviewed periodically about the health status and development of the participant
• keep diaries and complete periodic questionnaires regarding participant symptoms

Enrollment: 12 estimated patients

Sex: All

Ages: 2 to 25 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• The participant has a TCF4 gene mutation confirmed as "pathogenic" or "likely pathogenic" by whole exome sequencing, whole genome sequencing, gene panel, single gene testing, or microarray, performed at an accredited laboratory
• Clinical phenotype consistent with Pitt Hopkins Syndrome, in the opinion of the investigator
• The participant, or the participant's parent or legal guardian, is willing to provide access to prior medical records for the collection of demographics and diagnostic and treatment history

Exclusion criteria

• A deletion that includes the TCF4 gene that is over 12 Mbp in size
• Another genetic mutation or clinical comorbidity not associated with Pitt Hopkins Syndrome that could potentially confound interpretation of the study data
• A central nervous system structural or vascular abnormality that is a contraindication to the ICV administration procedure, including but not limited to: signs or symptoms of increased intracranial pressure, history of a space-occupying lesion, or presence of a ventricular shunt that would preclude ICV procedures or safety assessments, or increase risk to the participant
• Not able to receive prophylactic corticosteroids due to a medical contraindication or participant has a history of a condition that could worsen with corticosteroid therapy as assessed and determined by the Investigator
• Not able to undergo MRI procedures
• Cannot be anesthetized for the ICV injection

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Cohort 1 (MZ-1866)

Experimental group

Description:

Participants ages 12-25 years

Treatment:

Genetic: MZ-1866

Cohort 2 (MZ-1866)

Experimental group

Description:

Participants aged 2-11 years

Treatment:

Genetic: MZ-1866