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

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ClinicalTrials.gov Identifier: NCT05228145
Recruitment Status : Recruiting
First Posted : February 8, 2022
Last Update Posted : September 18, 2023
Sponsor:
Information provided by (Responsible Party):
Neurogene Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Neuronal Ceroid Lipofuscinosis CLN5 Genetic: NGN-101 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation cohort study of NGN-101 administered by intracerebroventricular (ICV) infusion and intravitreal (IVT) injection; cohorts will be assigned sequentially.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Intracerebroventricular and Intravitreal Administration of NGN-101 for Treatment of Neuronal Ceroid Lipofuscinosis (NCL) Subtype 5 (CLN5) Disease
Actual Study Start Date : January 31, 2022
Estimated Primary Completion Date : November 2028
Estimated Study Completion Date : November 2028

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 5 years (multiple visits) ]
    Incidence, type, severity, and frequency of TEAEs

  2. Incidence of Serious Adverse Events (SAEs) [ Time Frame: 5 years (multiple visits) ]
    Incidence, type, severity, and frequency of SAEs

  3. Incidence of clinical laboratory abnormalities [ Time Frame: 5 years (multiple visits) ]
    Incidence, type, severity, and frequency of clinical laboratory abnormalities

  4. Incidence of new nerve conduction study (NCS) abnormalities [ Time Frame: 5 years (multiple visits) ]
    Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities

  5. Incidence of new physical and neurologic exam abnormalities [ Time Frame: 5 years (multiple visits) ]
    Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities


Secondary Outcome Measures :
  1. Change in Hamburg Scale, Motor and Language domain scores [ Time Frame: 5 years (multiple visits) ]
    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)

  2. Change in Spectral Domain-Optical Coherence Tomography (SD-OCT) [ Time Frame: 5 years (multiple visits) ]
    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

  3. Change in Unified Batten Diseases Rating Scale (UBDRS) [ Time Frame: 5 years (multiple visits) ]
    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)

  4. Change in Caregiver global impression of change [ Time Frame: 5 years (multiple visits) ]
    Caregiver global impression of change throughout the study

  5. Change in visual acuity measurements [ Time Frame: 5 years (multiple visits) ]
    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)

  6. Change in color vision [ Time Frame: 5 years (multiple visits) ]
    Change from baseline in color vision measured using Ishihara color blindness testing


Eligibility Criteria
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Ages Eligible for Study:   3 Years to 9 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05228145


Contacts
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Contact: Contact Center +1 877-237-5020 medicalinfo@neurogene.com

Locations
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United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Amy Vierhile, RN         
United Kingdom
Great Ormond Street Hospital for Children Recruiting
London, United Kingdom, WC1N 3JH
Contact: Paul Gissen, MD         
Sponsors and Collaborators
Neurogene Inc.
Investigators
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Study Director: Xiomara Q. Rosales, MD Neurogene Inc.
More Information
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Responsible Party: Neurogene Inc.
ClinicalTrials.gov Identifier: NCT05228145    
Other Study ID Numbers: CLN5-200
First Posted: February 8, 2022    Key Record Dates
Last Update Posted: September 18, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Neurogene Inc.:
Batten Disease
Neuronal Ceroid Lipofuscinosis Disease
Neuronal Ceroid Lipofuscinosis Subtype 5 Disease
NCL
 Gene Therapy
Gene Transfer
CLN5
CLN
Additional relevant MeSH terms:
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Neuronal Ceroid-Lipofuscinoses
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Genetic Diseases, Inborn
 Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Metabolic Diseases