Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL)

• Register: ClinicalTrials.gov
• Last refreshed on: 8 February 2021
• Main ID: NCT01161576
• Date of registration: 22/03/2010
• Prospective Registration: Yes
• Primary sponsor: Weill Medical College of Cornell University
• Public title: Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL)
• Scientific title: Direct CNS Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human CLN2 cDNA to Children With Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL)
• Date of first enrolment: August 19, 2010
• Target sample size: 12
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01161576
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Ronald G Crystal, MD
• Affiliation: Weill Medical College of Cornell University

Key inclusion & exclusion criteria

Inclusion Criteria:

All individuals who meet the following criteria will be included without bias as to a
gender or race/ethnicity. Each case will be individually reviewed with the Eligibility
Committee comprised of 3 physicians other than the PI, including a pediatric neurosurgeon,
pediatric neurologist and general pediatrician.

1. Definitive diagnosis of LINCL, based on clinical phenotype and genotype. The genotype
must include at least one of the 5 most common CLN2 mutant genotypes: C3670T (nonsense
Arg208 to stop), G3556C (intron 7 splice), G5271C (Gln422His), T4396G (aberrant
splicing, intron 8) and G4655A (Cys365Tyr). If either parental allele is R447H, the
patient will not be included in the study. These account for a total of 83% of the
mutations in the study by Sleat et al and 82% of the mutations in our studies. The
study does not limit to one specific genotype (genetic constitution) since our data
regarding the natural history of the disease and the studies of Steinfeld, show that,
for these 5 genotypes (genetic constitution), LINCL subjects have similar clinical
course.

2. The subject must be between the age of 2 and 18 years.

3. Subjects will have an average total score of 4 - 12 on the Weill-Cornell LINCL scale,
and the total score should not be outside the 95th percentile confidence limits for
age based on our historic data.

4. The subject will not previously have participated in a gene transfer or stem cell
study.

5. 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, and both parents or legal guardians must give consent for their child's
participation.

6. Sexually active subjects will have to use contraception during the treatment and for 2
months after completion of the treatment.

7. If asymptomatic (i.e - An LINCL score of 12), has one older sibling who has a positive
genotype and has clinical manifestations of the disease.

Exclusion Criteria:

1. Presence of other significant medical or neurological conditions may disqualify the
subject from participation in this study, particularly those which would create an
unacceptable operative risk or risk to receiving the AAVrh.10CUhCLN2 vector, e.g.,
malignancy, congenital heart disease, liver or renal failure.

2. Subjects without adequate control of seizures.

3. Subjects with heart disease that would be a risk for anesthesia or a history of major
risk factors for hemorrhage.

4. Subjects who cannot participate in MRI studies.

5. Concurrent participation in any other FDA approved Investigational New Drug.

6. Subjects with history of prolonged bleeding or abnormal platelet function or taking
aspirin.

7. Renal disease or altered renal function as defined by serum creatinine > 1.5 mg/dl at
admission.

8. Abnormal serum sodium, potassium calcium, magnesium, phosphate at grade III or IV by
Division of AIDS Toxicity Scale.

9. Hepatic disease or altered liver function as defined by SGPT > 150 U/L, and or Total
Bilirubin > 1.3 mg/dL

10. Immunosuppression as defined by WBC < 3,000/µL at admission

11. Uncorrected coagulopathy during the baseline period defined as INR > 1.4; PTT > 35
sec; PLT < 100,000/mm3.

12. Anemia (hemoglobin < 11.0 g/dl at > 2 years of age, with normal serum iron studies).



Age minimum: 2 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Late-Infantile Neuronal Ceroid Lipofuscinosis

Batten Disease

Intervention(s)

Biological: AAVrh.10CUhCLN2 vector 9.0x10^11 genome copies

Biological: AAVrh.10CUhCLN2 vector 2.85x10^11 genome copies

Primary Outcome(s)

Disease progression based on change in MRI imaging parameter (% grey matter volume) from Baseline to 18 Months [Time Frame: 18 Months]

Disease progression based on change in MRI imaging parameter cortical apparent diffusion coefficient) from Baseline to 18 Months [Time Frame: 18 Months]

Change in Weill-Cornell LINCL scale from Baseline to 18 months [Time Frame: 18 Months]

Disease progression based on change in MRI imaging parameter (% ventricular volume) from Baseline to 18 Months [Time Frame: 18 Months]

Secondary Outcome(s)

Change in Quality of Life Survey from Baseline to 18 Months [Time Frame: 18 months]

Mullen Scale (developmental assessment) from Baseline to 18 Months [Time Frame: 18 months]

Secondary ID(s)

0810010013

UL1TR000457-06

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institutes of Health (NIH)