Overview

This trial is active, not recruiting.

Conditions batten disease, late infantile neuronal ceroid lipofuscinosis
Treatment aav2cuhcln2
Phase phase 1
Sponsor Weill Medical College of Cornell University
Collaborator Nathan's Battle Foundation
Start date June 2004
End date June 2019
Trial size 11 participants
Trial identifier NCT00151216, 0401007010, OBA-RAC 0312-619

Summary

The aim of this study is to treat the signs and symptoms of late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal inherited disease in the brain. This will be accomplished by using delivery of a gene (method called gene transfer) to administer to the brain an experimental drug called AAV2CUhCLN2, a gene transfer vector.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Expressing the Human CLN2 cDNA to the Brain of Children With Late Infantile Neuronal Ceroid Lipofuscinosis
aav2cuhcln2
gene transfer; one-time administration via neuro surgery procedure

Primary Outcomes

Measure
The primary endpoint for the trial is neurological assessment using the LINCL clinical rating scale at screening; pre-therapy; and 6 and 18 months post-vector administration.
time frame: at screening; pre-therapy; and 6 and 18 months post-vector administration

Secondary Outcomes

Measure
The secondary endpoint variable will be the MRI/MRS assessment of the CNS in regions of vector administration. This will be assessed at screening; pre-therapy; and 6 and 18 months post-vector administration.
time frame: at screening; pre-therapy; and 6 and 18 months post-vector administration

Eligibility Criteria

Male or female participants from 3 years up to 18 years old.

Inclusion Criteria: - A definitive diagnosis of late infantile neuronal ceroid lipofuscinosis - Between the age of 3 and 18 years - Not previously participated in a gene transfer study for LINCL. - Parents of study participants must agree to comply in good faith with the conditions of the study, including attending all of the required baseline and follow-up assessments. - Both parents or legal guardians must give consent for their child's participation in the research study. Exclusion Criteria: - Other significant medical or neurological conditions may disqualify the patient from participation in this study, particularly those which would create an unacceptable operative risk or risk to receiving the AAV2CUhCLN2 vector. - Individuals with heart disease that would be a risk for anesthesia. - History of hemorrhage or major risk factors for hemorrhage - Concurrent participation in any other FDA approved Investigational New Drug clinical protocol is not allowed, although the Principal Investigator will work with other doctors to accommodate specific requests (e.g., a study of nutritional supplements probably would not be a disqualification). - Individuals who have a (1) heart pacemaker and/or related implants, (2) metal fragment/chip in the eye or other sites, (3) an aneurysm clip in their brain, and (4) metallic inner ear implants.

Additional Information

Official title Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Expressing the Human CLN2 cDNA to the Brain of Children With Late Infantile Neuronal Ceroid Lipofuscinosis
Principal investigator Ronald G. Crystal, MD
Description Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal childhood neurodegenerative lysosomal storage disease with no known therapy. There are estimated to be 200 to 300 children in the USA at any one time with the disease. LINCL is a genetic disease resulting from mutations in the CLN2 gene. The CLN2 gene encodes a protein tripeptidyl peptidase-I (TPP-I) which is absent/deficient in children with LINCL. This absence/deficiency of TPP-I results in lysosomal storage and subsequent cell death (especially neurons). The children with LINCL are chronically ill, with a progressive CNS disorder that invariably results in death, typically by age 8 to 12. This clinical study will evaluate the concept that persistent expression of the normal CLN2 cDNA in the CNS will result in the production of sufficient amounts of TPP-I to prevent further loss of neurons, and hence limit disease progression. To assess this concept, an adeno-associated virus vector encoding the normal human CLN2 gene (AAV2CUhCLN2) will be used as a vehicle to deliver and express the human CLN2 cDNA in the brain of children with LINCL. The proposed study will include 11 individuals and will be divided into two parts. Group A, to be studied first, will include 5 individuals with the severe form of the disease. Group B of the trial will include 6 individuals with a moderate form of the disease. Following direct intracranial administration of the vector, there will be neurological assessment using the LINCL clinical rating scale and magnetic resonance imaging/magnetic resonance spectroscopy assessment of the CNS in regions of vector administration. The data generated will help evaluate two hypotheses: (1) that it is safe to carry out direct intracranial administration of the AAV2CUhCLN2 vector to the CNS of individuals with LINCL; and (2) that administration of the AAV2CUhCLN2 vector will slow down or halt the progression of the disease in the central nervous system.
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by Weill Medical College of Cornell University.