Gene Therapy Study for Children With CLN5 Batten Disease

NCT05228145 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CLN5-200
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Neuronal Ceroid Lipofuscinosis CLN5

Keywords

Batten Disease; Neuronal Ceroid Lipofuscinosis Disease; Neuronal Ceroid Lipofuscinosis Subtype 5 Disease; NCL; Gene Therapy; Gene Transfer; CLN5; CLN

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• Change in Hamburg Scale, Motor and Language domain scores

  5 years (multiple visits)

• Change in Spectral Domain-Optical Coherence Tomography (SD-OCT)

  5 years (multiple visits)

• Change in Unified Batten Diseases Rating Scale (UBDRS)

  5 years (multiple visits)

• Change in Caregiver global impression of change

  5 years (multiple visits)

• Change in visual acuity measurements

  5 years (multiple visits)

Study Arms (3)

Cohort 1

EXPERIMENTAL

The study treatment is a recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).

Genetic: NGN-101

Cohort 2

EXPERIMENTAL

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

Cohort 3

EXPERIMENTAL

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

Interventions

NGN-101 GENETIC

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.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 3 Years - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Neurogene Inc.: lead

Study Sites (2)

University of Rochester

Rochester, New York, 14642, United States

Location

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

Related Publications (2)

• Murray SJ, Wellby MP, Barrell GK, Russell KN, Deane AR, Wynyard JR, Gray SJ, Palmer DN, Mitchell NL. Efficacy of dual intracerebroventricular and intravitreal CLN5 gene therapy in sheep prompts the first clinical trial to treat CLN5 Batten disease. Front Pharmacol. 2023 Oct 24;14:1212235. doi: 10.3389/fphar.2023.1212235. eCollection 2023.

  PMID: 37942487 DERIVED

• Mitchell NL, Murray SJ, Wellby MP, Barrell GK, Russell KN, Deane AR, Wynyard JR, Palmer MJ, Pulickan A, Prendergast PM, Casy W, Gray SJ, Palmer DN. Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease. Front Genet. 2023 Aug 8;14:1212228. doi: 10.3389/fgene.2023.1212228. eCollection 2023.

  PMID: 37614821 DERIVED

MeSH Terms

Conditions

Neuronal Ceroid-Lipofuscinoses

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Effie Albanis, MD

  Neurogene Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation cohort study of NGN-101 administered by intracerebroventricular (ICV) infusion and intravitreal (IVT) injection; cohorts will be assigned sequentially.

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: February 8, 2022
• Study Start: January 31, 2022
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: August 12, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (1)