Gene Therapy Study for Children With CLN5 Batten Disease (CLN5-200)

A Phase 1/2 Intracerebroventricular and Intravitreal Administration of NGN-101 for Treatment of Neuronal Ceroid Lipofuscinosis (NCL) Subtype 5 (CLN5) Disease

This is a prospective, non-randomized, open-label, dose escalation study of a single administration of gene therapy in children who are 3 to 9 years old with Neuronal Ceroid Lipofuscinosis (Batten) Subtype 5 (CLN5) disease.

Study Overview

• Status: Recruiting
• Conditions: Neuronal Ceroid Lipofuscinosis CLN5
• Intervention / Treatment: Genetic: NGN-101

Detailed Description

The study is a first in human (FIH) open-label, dose escalation study designed to assess the safety and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9) carrying the gene encoding human ceroid-lipofuscinosis neuronal protein 5 (CLN5) in subjects with CLN5 Batten disease. The study treatment will be delivered via intracerebroventricular (ICV) and intravitreal (IVT) injection on the same day. Each participant will be followed for safety and efficacy for 5 years after treatment. Efficacy assessments in this study will evaluate motor, language, visual and cognitive function.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Contact Center; Phone Number: +1 877-237-5020; Email: medicalinfo@neurogene.com

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Recruiting
    • Great Ormond Street Hospital for Children
    • Contact: Paul Gissen, MD
• United States
  • New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester
      • Contact: Amy Vierhile, RN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 9 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Age from 3 to 9 years (Child)
• Molecular genetic diagnosis of the CLN5 gene
• Confirmed clinical diagnosis of CLN5 disease
• Impaired motor and/or language function and/or impaired visual acuity
• Written informed consent from parent or legal guardian and assent from study participant, if appropriate
• Able to comply with protocol required assessments (laboratory sample collection, lumbar puncture (LP), nerve conduction studies (NCS), magnetic resonance imaging (MRI), etc.), which may require sedation or general anesthesia
• Able to walk with or without assistance (assistance may include a walker, braces, or with one hand held)
• Agree to reside within a 1-hour drive of the study site for at least 6 months following treatment (or a safely drivable distance for the study participant and caregivers according to investigator's discretion)

Exclusion Criteria

• Has another neurologic disease or illness that may have caused cognitive decline before study entry
• Known pathogenic or clinically suspected variant in a seizure associated genetic mutation besides CLN5
• Any active infections or severe infections within the 30 days prior to study treatment administration
• Presence of a concomitant medical condition that precludes intracerebroventricular (ICV) injection, lumbar puncture (LP), or use of anesthetics needed for study-related procedures
• Presence of any concomitant medical conditions that preclude intravitreal (IVT) administration
• Has status epilepticus that lasts longer than 5 minutes or having more than 1 seizure within a 5-minute period, without returning to a normal level of consciousness between episodes within 12 weeks before study treatment
• Total anti-AAV9 antibody titer greater than 1:400
• Any anticipated need for major surgery in the next 24 months
• Participation in an Investigational New Drug, Investigational Device Exemption, or equivalent clinical study in the past 6 months
• Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered
• Participation in other investigational studies and non-interventional studies that have similar study assessments as this protocol while the study participant is enrolled in this study with the exception of sister studies sponsored by Neurogene
• History of or current chemotherapy, radiotherapy, or other immunosuppressive therapy within the past 3 months
• Use of prohibited medications
• Immunizations of any kind in the 45 days prior to study treatment
• Requiring daytime or nighttime ventilatory support at the time of Screening
• Any item which would exclude the study participant from being able to undergo brain magnetic resonance imaging (MRI) according to local institutional policy
• Known allergies or hypersensitivities to the required immunosuppression regime

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; The study treatment is a recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).	Genetic: NGN-101; Participants with confirmed mutations in the CLN5 gene who meet all the inclusion and none of the exclusion criteria will be treated with a single intracerebroventricular (ICV) dose and a single intravitreal (IVT) dose of the study treatment.
Experimental: Cohort 2; The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).	Genetic: NGN-101; Participants with confirmed mutations in the CLN5 gene who meet all the inclusion and none of the exclusion criteria will be treated with a single intracerebroventricular (ICV) dose and a single intravitreal (IVT) dose of the study treatment.
Experimental: Cohort 3; The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon- optimized human CLN5 transgene (hCLN5opt).	Genetic: NGN-101; Participants with confirmed mutations in the CLN5 gene who meet all the inclusion and none of the exclusion criteria will be treated with a single intracerebroventricular (ICV) dose and a single intravitreal (IVT) dose of the study treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events (TEAEs)	Incidence, type, severity, and frequency of TEAEs	5 years (multiple visits)
Incidence of Serious Adverse Events (SAEs)	Incidence, type, severity, and frequency of SAEs	5 years (multiple visits)
Incidence of clinical laboratory abnormalities	Incidence, type, severity, and frequency of clinical laboratory abnormalities	5 years (multiple visits)
Incidence of new nerve conduction study (NCS) abnormalities	Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities	5 years (multiple visits)
Incidence of new physical and neurologic exam abnormalities	Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities	5 years (multiple visits)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamburg Scale, Motor and Language domain scores	Change from baseline in Hamburg Scale, Motor and Language domain scores (each domain is rated from 0 to 3, with 3 reflecting normal function for age and 0 reflecting complete loss of function)	5 years (multiple visits)
Change in Unified Batten Diseases Rating Scale (UBDRS)	Change from baseline in total score and individual domains of the Unified Batten Diseases Rating Scale (UBDRS; total score 0 to 277, with higher scores indicating worse function)	5 years (multiple visits)
Change in Caregiver global impression of change	Caregiver global impression of change throughout the study	5 years (multiple visits)
Change in visual acuity measurements	Change from baseline in visual acuity measured using Teller acuity cards, Lea symbol chart, Landolt C chart, or low contrast visual acuity (measure to be used will depend on subject's level of cognitive and visual function)	5 years (multiple visits)
Change in color vision	Change from baseline in color vision measured using Ishihara color blindness testing	5 years (multiple visits)
Change in Spectral Domain-Optical Coherence Tomography (SD-OCT)	Change from baseline in SD-OCT parameters including Ellipsoid Zone (EZ) defect area measurements, macular volume and thickness, retinal nerve fiber layer thickness, and ganglion cell layer thickness	5 years (multiple visits)

Collaborators and Investigators

• Sponsor: Neurogene Inc.
• Investigators: Study Director: Xiomara Q. Rosales, MD, Neurogene Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2022
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: December 17, 2021
• First Submitted That Met QC Criteria: February 4, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Gene Therapy; Batten Disease; Gene Transfer; NCL; CLN; Neuronal Ceroid Lipofuscinosis Disease; Neuronal Ceroid Lipofuscinosis Subtype 5 Disease; CLN5
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Lipid Metabolism Disorders; Lipidoses; Lipid Metabolism, Inborn Errors; Neuronal Ceroid-Lipofuscinoses
• Other Study ID Numbers: CLN5-200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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