A Natural History Study of Late Infantile Variant CLN5 And CLN7 Disease

• ClinicalTrials.gov Identifier: NCT03822650
• Recruitment Status: Recruiting
• First Posted: January 30, 2019
• Last Update Posted: October 14, 2020
• Sponsor: Neurogene Inc.
• Information provided by (Responsible Party): Neurogene Inc.

Study Description

Brief Summary:

CLN5 and CLN7 are forms of Batten Disease, and neurodegenerative disorders in children causing psychomotor regression, seizures, blindness, loss of ambulation and premature death, and have no available treatments.

The purpose of this study is to investigate the clinical characteristics and natural clinical progression of symptoms in individuals with CLN5 and CLN7. 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; Ceroid Lipofuscinosis, Neuronal 7

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.

CLN7 is another type of NCL caused by homozygous or bi-allelic heterozygous variants in CLN7/MFSD8 gene, whose function is poorly characterized. CLN7 presents with neurological signs, including blindness, seizures, progressive deterioration in intellectual and motor capabilities, culminating in premature death in the first or second decade of life.

No investigational product will be provided in the study.

Study Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Natural History and Outcome Measure Discovery Study of Variant Late Infantile Neuronal Ceroid Lipofuscinosis Type 5 (CLN5) and Variant Late Infantile Neuronal Ceroid Lipofuscinosis Type 7 (CLN7)
• Actual Study Start Date: March 13, 2019
• Estimated Primary Completion Date: June 2026
• Estimated Study Completion Date: December 2026

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Unified Batten Disease Rating Scale (UBDRS) [ Time Frame: 5 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: 5 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: 5 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, 2rd or 3rd Edition (Vineland-II, Vineland-3) [ Time Frame: 5 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. NEPSY, 2nd Edition (NEPSY-2) * [ Time Frame: 5 years ]
   Neuropsychological assessment to evaluate language skills for individuals 3-16 years of age.
4. Woodcock-Johnson-IV Tests of Cognitive Abilities (WJ-IV)* [ Time Frame: 5 years ]
   Evaluates strengths and weaknesses among cognitive abilities in subjects 2-90 years of age. A higher score generally corresponds with higher function.
5. Bayley Scales of Infant and Toddler Development Test, 3rd edition (Bayley-3) * [ Time Frame: 5 years ]
   Developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

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 or CLN7.

Criteria

Inclusion Criteria:

• Participants must have a diagnosis of CLN5 or CLN7 based on clinical presentation and genetic testing (known or suspected pathogenic mutation in CLN5 or CLN7/MFSD8 gene).

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 585-275-4762 amy_vierhile@urmc.rochester.edu

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: STU-2018-0226
• First Posted: January 30, 2019
• Last Update Posted: October 14, 2020
• Last Verified: October 2020

• 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