A Natural History Study of Neuronal Ceroid Lipofuscinosis Type 5 (CLN5)

• ClinicalTrials.gov Identifier: NCT03822650
• Recruitment Status: Recruiting
• First Posted: January 30, 2019
• Last Update Posted: March 9, 2023
• Sponsor: Neurogene Inc.
• Information provided by (Responsible Party): Neurogene Inc.

Study Description

Brief Summary:

CLN5 is a form of Batten Disease, a neurodegenerative disorder in children causing psychomotor regression, seizures, blindness, loss of ambulation and premature death, and has no available treatments.

The purpose of this study is to investigate the clinical characteristics and natural clinical progression of symptoms in individuals with CLN5. This natural history study is important to better understand disease course to be able to determine clinically relevant outcome measures for use in future clinical trials.

Condition or disease
Ceroid Lipofuscinosis, Neuronal 5

Detailed Description:

Neuronal Ceroid Lipofuscinosis (NCL) are comprised of a group of fatal neurodegenerative diseases caused by mutations in an enzyme or protein which results in the accumulation of toxic deposits in the eye, brain, skin, muscle and other cells.

CLN5 is a type of NCL, caused by homozygous or bi-allelic heterozygous variants in the CLN5 gene. Lack of CLN5 protein impairs the breakdown of certain proteins, leads to defective lysosomal trafficking, resulting in accumulation of toxic material and subsequent cell damage. CLN5 disease presents in childhood with neurological findings including motor clumsiness and attention disturbances, followed by progressive visual failure, psychomotor depression, epilepsy, and premature death.

No investigational product will be provided in the study.

Study Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: A Natural History and Outcome Measure Discovery Study of Neuronal Ceroid Lipofuscinosis Type 5 (CLN5)
• Actual Study Start Date: March 13, 2019
• Estimated Primary Completion Date: January 2026
• Estimated Study Completion Date: January 2026

Groups and Cohorts

Group/Cohort
Prospective; Subjects who meet eligibility criteria and enroll in the prospective arm will be assessed every 6 months ± 4 weeks for a period of up to 3 years, according to the Schedule of Assessments. Subjects in the Prospective arm may also participate in the Retrospective arm.
Retrospective; Upon confirmation of eligibility criteria, the site will obtain an Informed Consent/Assent form and release of medical records from the subject/legally authorized representative to allow review of the medical records from the subject's primary care physician and/or specialists to confirm the CLN5 diagnosis and disease course. To facilitate collection of the medical records, a caregiver interview will be completed at initial enrollment then once yearly for up to 3 years.

Outcome Measures

Primary Outcome Measures :

1. Unified Batten Disease Rating Scale (UBDRS) [ Time Frame: 3 years ]
   Disease-specific clinical assessment used to assess physical, seizure, behavioral and functional capabilities. For physical assessments scores range from 0 to 4 with the score of 4 being most severe.
2. Late Infantile Neuronal Ceroid Lipofuscinosis Rating Scale (Hamburg Scale) [ Time Frame: 3 years ]
   Disease specific tool used to capture 4 domains including motor function, seizures, visual function and language. Each sub-scale can be scored from 0-3 points in which 0 represents loss of function.

Secondary Outcome Measures :

1. Electroencephalography (EEG) [ Time Frame: 3 years ]
   EEG records electrical brain activity and Interictal discharges (location, focal/generalized, etc) will be compared to baseline and characterized over time.
2. Vineland Adaptive Behavior Scale, 2nd Edition (Vineland-II) [ Time Frame: 3 years ]
   Standard assessment measuring communication, socializing, and daily living skills to assess their overall adaptive functioning for individuals up to 90 years of age. A higher score generally corresponds with higher adaptive function.
3. Caregiver Global Impression of Change (CaGI-C) [ Time Frame: 3 years ]
   The CaGI-C is a caregiver reported outcome measure designed to assess any change in the subject's presentation over the preceding 7 days, as compared to the previous visit.

Biospecimen Retention:   Samples With DNA

whole blood

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with a confirmed genetic diagnosis of CLN5.

Criteria

Inclusion Criteria:

1. Age at disease onset of ≤ 5 years of age.
2. Molecular genetic diagnosis confirming the presence of pathogenic or likely pathogenic variant(s) on both alleles (biallelic) of the CLN5 gene.

For Prospective Arm only:

1. Subject age of ≤ 9 years.
2. Hamburg motor and vision score of ≥ 1 at time of consent.
3. Subject must have a caregiver available to support the subject and attend visits with the subject.

Exclusion Criteria - All Subjects:

1. Has another neurologic disease or illness that may have caused cognitive decline before study entry.
2. Has a known pathogenic or clinically suspected mutation in a seizure associated genetic mutation besides CLN5.
3. Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered.
4. Participation in other investigational studies and non-interventional studies that have similar study assessments as this protocol while the subject is enrolled in this study is prohibited.

Contacts and Locations

Contacts

Contact: Contact Center; 877-237-5020; medicalinfo@neurogene.com

Locations

United States, New York

University of Rochester Medical Center; Recruiting

Rochester, New York, United States, 14642

Contact: Amy Vierhile, RN

Sponsors and Collaborators

Neurogene Inc.

Investigators

• Study Director: Elise Beausoleil; Neurogene Inc.

More Information

• Responsible Party: Neurogene Inc.
• ClinicalTrials.gov Identifier: NCT03822650
• Other Study ID Numbers: CLN-100
• First Posted: January 30, 2019
• Last Update Posted: March 9, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Neurogene Inc.:

CLN; NCL; Batten

Additional relevant MeSH terms:

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