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

NCT ID: NCT07135050

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2029-07-31

Brief Summary

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

Conditions

Pitt Hopkins Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (MZ-1866)

Participants ages 12-25 years

Group Type: EXPERIMENTAL

MZ-1866

Intervention Type: GENETIC

AAV-9 gene therapy delivered by intracerebroventricular injection

Cohort 2 (MZ-1866)

Participants aged 2-11 years

Group Type: EXPERIMENTAL

MZ-1866

Intervention Type: GENETIC

AAV-9 gene therapy delivered by intracerebroventricular injection

Interventions

MZ-1866

AAV-9 gene therapy delivered by intracerebroventricular injection

Intervention Type: GENETIC

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mahzi Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Rush University Medical Center

Chicago, Illinois, United States

Countries

United States

Central Contacts

Emily Radomile

Role: CONTACT

clinicaltrials@mahzi.com

1-844-446-2494

Facility Contacts

Matt Thura

Role: primary

matt.thura@ucsf.edu

Milana Milic

Role: primary

milana_milic@rush.edu

Other Identifiers

MZ1866-CL101

Identifier Type: -

Identifier Source: org_study_id