AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01414985
• Date of registration: 13/12/2010
• Prospective Registration: No
• Primary sponsor: Weill Medical College of Cornell University
• Public title: AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis
• 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 LINCL With Uncommon Genotypes and/or Moderate to Severe Impairment
• Date of first enrolment: April 15, 2010
• Target sample size: 8
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01414985
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

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

Key inclusion & exclusion criteria

Inclusion criteria.

1. Definitive diagnosis of LINCL, based on clinical phenotype and genotype. The study
does not limit to one specific genotype (genetic constitution).

2. The subject must be between the age of 3 and 18 years.

3. Subjects will have an average total score of less than 4 but at least 1, and/or an
uncommon genotype defined as any genotype that does not include at least one of the 5
most common mutant CLN2 genotypes: C3670T (nonsense Arg208 to stop), G3556C (intron 7
splice), G5271C (Gln422His), T4396G (aberrant splicing, intron8), and G4655A. The
total LINCL 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.

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
T.Bilirubin> 1.3 mg/dL

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

11. Uncorrected coagulopathy during the baseline period defined as INR > 1.4; PTT > 35
sec; PLT < 150,000/mm3

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



Age minimum: 3 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Batten Disease

Late Infantile Neuronal Ceroid Lipofuscinosis

Intervention(s)

Biological: AAVrh.10CUCLN2

Primary Outcome(s)

Safety, as measured by MRI [Time Frame: Screening, Pre-transfer, Months 6, 12 and 18]

Change in CNS function, as measured by the Weill Cornell LINCL Scale [Time Frame: Screening, Pre-transfer, Months 1, 6, 12 and 18]

Secondary Outcome(s)

Change in psychological development, as measured by the Mullen Scale [Time Frame: Screening, Pre-transfer (optional) and Month 18]

Change in Quality of Life, as measured by the Child Health Questionnaire (CHQ) or Infant Toddler Quality of Life (ITQoL) (depending on age) [Time Frame: Screening, Pre-transfer (optional) and Month 18]

Secondary ID(s)

1005011054

IND 13951

Source(s) of Monetary Support

Please refer to primary and secondary sponsors