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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 LINCL With Uncommon Genotypes and/or Mod

Brief Summary:

The investigators propose to assess the safety and efficacy of a new administration method to deliver a biologic to children with a form of Batten disease using an experimental gene transfer procedure. This gene transfer procedure consists of delivering a good copy of the mutated gene to the nerve cells via a virus. These children are born with genetic changes called mutations that result in the inability of the brain to properly recycle proteins. The recycling failure leads to death of the nerve cells in the brain and progressive loss of brain function. Children with Batten disease are normal at birth but by age 2 to 4 have motor and vision problems which progress rapidly to death at age approximately 10 years old. There are no therapies available to treat the disease.

The investigators previous clinical trial used a virus called adeno-associated virus 2 (AAV2) as the gene delivery system. That study showed that viral delivery of the gene was safe and showed small, but significant benefits to the recipient. The investigators currently have an IRB approved protocol which uses a slightly different virus called AAVrh.10 as the gene delivery system. This 3rd protocol proposes to use the same virus AAVrh.10 as the gene delivery system and has expanded the eligibility criteria.

Detailed Summary:

This study is designed to run parallel to our currently IRB approved protocol #0810010013 entitled "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," which will assess the safety and efficacy of the virus AAVrh.10 to deliver the CLN2 gene to children in the early stages of the disease. This current study proposes to assess the safety and efficacy of the administration of the same biologic to children who do not fit the criteria for IRB protocol #0810010013.

The differences between protocol #0810010013 and the proposed "parallel" protocol is that inclusion criteria have been modified to include children with any genotype (not only the 5 most common genotypes as in the currently approved protocol) and/or those who score below a 6 but at least a 1 on the Weill Cornell LINCL scale. The reason for expanding the eligibility criteria is to obtain a range of safety data for all children with LINCL, not only those with limited genotype and/or severity. Only 8 subjects will be administered the gene transfer vector in this "parallel" protocol. Subjects will be accrued through IRB approved protocol #0901010186 entitled, "Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis (2)." Those who do not fit all criteria for the already approved gene transfer protocol (#0810010013) may have the opportunity to be enrolled in this proposed "parallel protocol" (Figure 1). The subjects in the new protocol will be compared to the 16 treated and 16 untreated children enrolled in IRB protocol #0810010013 and #0901010186, respectively.

Current Primary Outcome: Weill Cornell LINCL Scale [ Time Frame: Month 1, 6, 12 and 18 ]

Original Primary Outcome:

• Weill Cornell LINCL Scale [ Time Frame: Day 14, Month 6, 12, Month 18 ]
  The Weill Cornell LINCL scale, a 12 point scale which combines assessment of feeding, gait, motor and language to give an overall assessment of various CNS functions (Appendix II for the paper describing the scale and Appendix VI for the scale)27. This rating scale evaluation will be performed by 2 independent pediatricians, on the basis of a videotaped evaluation. If the 2 independent scores differ by 1 or less they will be averaged and if they differ by greater than 1 point, a consensus will be obtained by a 3rd pediatrician.This outcome measure will look at changes over time.
• MRI [ Time Frame: Day 14, Month 1, Month 6, 12, 18 ]
  3 imaging parameters (% gray matter volume, % ventricular volume and cortical apparent diffusion coefficient) correlate with age and the Weill Cornell LINCL scale. These 3 imaging parameters will be used to assess disease progression (control protocol) and safety of the gene transfer vector (vector protocol) over time. In addition to these imaging parameters we will also perform magnetic resonance spectroscopy (MRS) but the data obtained from this will be for information only for method development. This outcome measure will look at changes over time.

Current Secondary Outcome:

• Child Health Questionnaire [ Time Frame: Month 1, 6, 12 and 18 ]
  The CHQ or ITQoL, a quality of life questionnaire which will be completed by at least one parent/legal guardian at the time of the LINCL patients' visits to Weill Cornell28,29; we will administer this survey independently to each parent to minimize observer bias if both parents are present. This outcome measure looks at a change over time.
• Mullen Scale [ Time Frame: Month 1, 6, 12 and 18 ]
  The Mullen scale, a pediatric developmental psychological rating scale; will be administered by a developmental psychologist, and be videotaped. This outcome measure will look at changes over time.
• MRI [ Time Frame: Month 6, 12 and 18 ]
  3 imaging parameters (% gray matter volume, % ventricular volume and cortical apparent diffusion coefficient) correlate with age and the Weill Cornell LINCL scale. These 3 imaging parameters will be used to assess disease progression (control protocol) and safety of the gene transfer vector (vector protocol) over time. In addition to these imaging parameters we will also perform magnetic resonance spectroscopy (MRS) but the data obtained from this will be for information only for method development. This outcome measure will look at changes over time.

Original Secondary Outcome:

• Child Health Questionnaire [ Time Frame: Day 0, Month 18 ]
  The CHQ or ITQoL, a quality of life questionnaire which will be completed by at least one parent/legal guardian at the time of the LINCL patients' visits to Weill Cornell28,29; we will administer this survey independently to each parent to minimize observer bias if both parents are present. This outcome measure looks at a change over time.
• Mullen Scale [ Time Frame: Day 0, Month 18 ]
  The Mullen scale, a pediatric developmental psychological rating scale; will be administered by a developmental psychologist, and be videotaped. This outcome measure will look at changes over time.

Dates:
Date Received: December 13, 2010
Date Started: December 2010
Date Completion: December 2022
Last Updated: May 23, 2017
Last Verified: May 2017