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

Purpose

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

Condition

  • Pitt Hopkins Syndrome

Eligibility

Eligible Ages
Between 2 Years and 25 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1 (MZ-1866)
Participants ages 12-25 years
  • Genetic: MZ-1866
    AAV-9 gene therapy delivered by intracerebroventricular injection
Experimental
Cohort 2 (MZ-1866)
Participants aged 2-11 years
  • Genetic: MZ-1866
    AAV-9 gene therapy delivered by intracerebroventricular injection

Recruiting Locations

UCSF Benioff Children's Hospital Oakland
Oakland 5378538, California 5332921 94609
Contact:
Matt Thura
matt.thura@ucsf.edu

Children's Hospital Colorado
Aurora 5412347, Colorado 5417618 80045
Contact:
Sky Gould
750-777-1583
sky.gould@childrenscolorado.org

More Details

Status
Recruiting
Sponsor
Mahzi Therapeutics

Study Contact

Emily Radomile
1-844-446-2494
clinicaltrials@mahzi.com