search
Back to results

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

Primary Purpose

Neuronal Ceroid Lipofuscinosis CLN5

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
NGN-101
Sponsored by
Neurogene Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuronal Ceroid Lipofuscinosis CLN5 focused on measuring Batten Disease, Neuronal Ceroid Lipofuscinosis Disease, Neuronal Ceroid Lipofuscinosis Subtype 5 Disease, NCL, Gene Therapy, Gene Transfer, CLN5, CLN

Eligibility Criteria

3 Years - 9 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • Age from 3 to 8 years (Child)
  • Molecular genetic diagnosis of the CLN5 gene
  • Confirmed clinical diagnosis of CLN5 disease
  • Impaired motor and/or language function and 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), electroencephalogram (EEG), 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 mutation 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 30 days 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
  • 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 30 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

Sites / Locations

  • University of RochesterRecruiting
  • Great Ormond Street Hospital for ChildrenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Incidence of Treatment Emergent Adverse Events (TEAEs)
Incidence, type, severity, and frequency of TEAEs
Incidence of Serious Adverse Events (SAEs)
Incidence, type, severity, and frequency of SAEs
Incidence of clinical laboratory abnormalities
Incidence, type, severity, and frequency of clinical laboratory abnormalities
Incidence of new nerve conduction study (NCS) abnormalities
Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities
Incidence of new physical and neurologic exam abnormalities
Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities

Secondary Outcome Measures

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)
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
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)
Change in Caregiver global impression of change
Caregiver global impression of change throughout the study
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)
Change in color vision
Change from baseline in color vision measured using Ishihara color blindness testing

Full Information

First Posted
December 17, 2021
Last Updated
September 14, 2023
Sponsor
Neurogene Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT05228145
Brief Title
Gene Therapy Study for Children With CLN5 Batten Disease
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 31, 2022 (Actual)
Primary Completion Date
November 2028 (Anticipated)
Study Completion Date
November 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neurogene Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuronal Ceroid Lipofuscinosis CLN5
Keywords
Batten Disease, Neuronal Ceroid Lipofuscinosis Disease, Neuronal Ceroid Lipofuscinosis Subtype 5 Disease, NCL, Gene Therapy, Gene Transfer, CLN5, CLN

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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)
Allocation
Non-Randomized
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
The study treatment is a recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon- optimized human CLN5 transgene (hCLN5opt).
Intervention Type
Genetic
Intervention Name(s)
NGN-101
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Treatment Emergent Adverse Events (TEAEs)
Description
Incidence, type, severity, and frequency of TEAEs
Time Frame
5 years (multiple visits)
Title
Incidence of Serious Adverse Events (SAEs)
Description
Incidence, type, severity, and frequency of SAEs
Time Frame
5 years (multiple visits)
Title
Incidence of clinical laboratory abnormalities
Description
Incidence, type, severity, and frequency of clinical laboratory abnormalities
Time Frame
5 years (multiple visits)
Title
Incidence of new nerve conduction study (NCS) abnormalities
Description
Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities
Time Frame
5 years (multiple visits)
Title
Incidence of new physical and neurologic exam abnormalities
Description
Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities
Time Frame
5 years (multiple visits)
Secondary Outcome Measure Information:
Title
Change in Hamburg Scale, Motor and Language domain scores
Description
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)
Time Frame
5 years (multiple visits)
Title
Change in Spectral Domain-Optical Coherence Tomography (SD-OCT)
Description
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
Time Frame
5 years (multiple visits)
Title
Change in Unified Batten Diseases Rating Scale (UBDRS)
Description
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)
Time Frame
5 years (multiple visits)
Title
Change in Caregiver global impression of change
Description
Caregiver global impression of change throughout the study
Time Frame
5 years (multiple visits)
Title
Change in visual acuity measurements
Description
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)
Time Frame
5 years (multiple visits)
Title
Change in color vision
Description
Change from baseline in color vision measured using Ishihara color blindness testing
Time Frame
5 years (multiple visits)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
9 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Contact Center
Phone
+1 877-237-5020
Email
medicalinfo@neurogene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiomara Q. Rosales, MD
Organizational Affiliation
Neurogene Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy Vierhile, RN
Facility Name
Great Ormond Street Hospital for Children
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Gissen, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Gene Therapy Study for Children With CLN5 Batten Disease

We'll reach out to this number within 24 hrs