Phase 1/2 Study of FRF-001, an AAV-9 Gene Therapy, in Patients With FOXG1 Syndrome (FS)

An Open-Label First-in-Human Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of FRF-001, an AAV-9 Gene Therapy Administered by Intracerebroventricular Injection in Participants With FOXG1 Syndrome

The goal of this clinical trial is to learn if FRF-001 is a safe, tolerable, and efficacious treatment for children and adults with FOXG1 syndrome.

Study Overview

• Status: Not yet recruiting
• Conditions: FOXG1 Syndrome
• Intervention / Treatment: Genetic: FRF-001

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Gai Ayalon; Phone Number: 650-665-0310; Email: clinical@foxg1research.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must have a FOXG1 mutation confirmed as likely pathogenic or pathogenic by whole exome sequencing, whole genome sequencing, gene panel, single gene testing, or microarray performed at an accredited lab, with clinical phenotype consistent with FS in the opinion of the investigator.
• The participant, or the participant's parent or legal guardian, is registered at the time of signing the informed consent in the FRF Citizen Natural History Study.
• The participant, or the participant's parent, legal guardian, or caregiver are willing and able to complete all aspects of the study, adhere to the study visit schedule, and comply with all assessments.

Exclusion Criteria:

• Another genetic mutation or clinical comorbidity which could potentially confound the typical FOXG1 syndrome phenotype; FOXG1 gene duplication; or FOXG1 gene deletions that include regions outside of the FOXG1 coding region.
• Prior treatment with a gene, cell therapy, or investigational treatment for FS.
• Concurrent enrollment in another clinical study unless it is observational (noninterventional) and the study that does not interfere with the requirements of the current protocol and does not have the potential to impact the evaluation of safety or efficacy of FRF-001.
• Any current or prior condition or contraindication that would render the participant unable to safely receive prophylactic corticosteroids, as assessed and determined by the Investigator.
• Contraindications to or unwilling to undergo MRI or lumbar puncture (LP) procedures.
• Any medical condition, comorbidity, or anatomical abnormality that, in the opinion of the Investigator and/or the attending anesthesiologist, would contraindicate the safe administration of sedation or general anesthesia required for study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Genetic: FRF-001; AAV-9 gene therapy delivered by intracerebroventricular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of single-dose FRF-001 in participants with FOXG1 syndrome	Incidence, severity, and causality of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and adverse events of special interest (AESIs)	Through Week 104
To evaluate the efficacy of single-dose FRF-001 in participants with FOXG1 syndrome	Attainment of motor milestones, as assessed by the Peabody Developmental Motor Scales - Third Edition (PDMS-3)	Week 52 and Week 104

Collaborators and Investigators

• Sponsor: FOXG1 Research Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 17, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: FRF-001-CL101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No