Gene Therapy Study for Children With CLN5 Batten Disease

Neuronal Ceroid Lipofuscinosis CLN5 Clinical Trial

— CLN5-200  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05228145
• Other study ID #: CLN5-200
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 31, 2022
• Est. completion date: November 2028

Study information

• Verified date: September 2023
• Source: Neurogene Inc.
• Contact: Contact Center
• Phone: +1 877-237-5020
• Email: medicalinfo[@]neurogene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: November 2028
• Est. primary completion date: November 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 9 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuronal Ceroid Lipofuscinosis CLN5
• Neuronal Ceroid-Lipofuscinoses

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	Great Ormond Street Hospital for Children	London
United States	University of Rochester	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Neurogene Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events (TEAEs)	Incidence, type, severity, and frequency of TEAEs	5 years (multiple visits)
Primary	Incidence of Serious Adverse Events (SAEs)	Incidence, type, severity, and frequency of SAEs	5 years (multiple visits)
Primary	Incidence of clinical laboratory abnormalities	Incidence, type, severity, and frequency of clinical laboratory abnormalities	5 years (multiple visits)
Primary	Incidence of new nerve conduction study (NCS) abnormalities	Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities	5 years (multiple visits)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	Change in Caregiver global impression of change	Caregiver global impression of change throughout the study	5 years (multiple visits)
Secondary	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)
Secondary	Change in color vision	Change from baseline in color vision measured using Ishihara color blindness testing	5 years (multiple visits)