Batten Disease Clinical Trial
Official 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)
Verified date | January 2021 |
Source | Weill Medical College of Cornell University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is a proposed follow up study on the investigators previous gene transfer human clinical trial entitled "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" (Weill Cornell IRB# 0401007010). As in the previous study, the investigators propose to administer a biologic by direct gene transfer into the brain and assess its safety on children with a fatal genetic disease of the central nervous system (CNS). The disease is Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL, a form of Batten disease). This will be accomplished by using delivery of a gene (method called gene transfer) to administer to the brain an experimental drug called AAVRh.10CUhCLN2, a gene transfer vector.
Status | Completed |
Enrollment | 12 |
Est. completion date | December 31, 2020 |
Est. primary completion date | January 5, 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 2 Years to 18 Years |
Eligibility | 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). |
Country | Name | City | State |
---|---|---|---|
United States | Weill Cornell Medical College | New York | New York |
Lead Sponsor | Collaborator |
---|---|
Weill Medical College of Cornell University | National Institutes of Health (NIH) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in Weill-Cornell LINCL scale from Baseline to 18 months | A clinical rating, 12 point scale which combines assessment of feeding, gait, motor and language to give an overall assessment of various CNS functions. | 18 Months | |
Primary | Disease progression based on change in MRI imaging parameter (% grey matter volume) from Baseline to 18 Months | Based on previous analyses, we have determined that 3 imaging parameters (% grey matter volume, MRI Assessment, % ventricular volume and cortical apparent diffusion coefficient) correlate best with age and with the Weill Cornell LINCL scale and will be used to assess disease progression and the effect of the gene transfer. | 18 Months | |
Primary | Disease progression based on change in MRI imaging parameter (% ventricular volume) from Baseline to 18 Months | Based on previous analyses, we have determined that 3 imaging parameters (% grey matter volume, MRI Assessment, % ventricular volume and cortical apparent diffusion coefficient) correlate best with age and with the Weill Cornell LINCL scale and will be used to assess disease progression and the effect of the gene transfer. | 18 Months | |
Primary | Disease progression based on change in MRI imaging parameter cortical apparent diffusion coefficient) from Baseline to 18 Months | Based on previous analyses, we have determined that 3 imaging parameters (% grey matter volume, MRI Assessment, % ventricular volume and cortical apparent diffusion coefficient) correlate best with age and with the Weill Cornell LINCL scale and will be used to assess disease progression and the effect of the gene transfer. | 18 Months | |
Secondary | Change in Quality of Life Survey from Baseline to 18 Months | The quality of life survey that will be completed by at least one parent/legal guardian at the screening visit and the month 18 visit will be either the Infant Toddler Quality of Life (ITQoL) questionnaire or the Child Health Questionnaire (CHQ), depending on the age of the subject. The ITQoL is administered to subjects up to the age of five and the CHQ is administered to subjects from age 5-18. | 18 months | |
Secondary | Mullen Scale (developmental assessment) from Baseline to 18 Months | Averaging the scores from the Mullen Scale | 18 months |
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