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

Plain-language summary

This study evaluates a gene therapy (delivering the CLN2 gene to the brain via an AAVrh.10 vector) administered to children with Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL, a type of Batten disease). It included children aged 3-18 with a clinically and genetically (CLN2) confirmed diagnosis. It was a Phase 1/Phase 2 study and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

PHASE1/PHASE2

Status

Completed

Sponsor

Weill Medical College of Cornell University

Intervention

AAVrh.10CUCLN2

Start date

4/15/2010

Estimated completion

2/8/2017

Countries

United States

Related genes

Locations

• New York, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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)