AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis
Condition: Late Infantile Neuronal Ceroid Lipofuscinosis; Batten Disease
MeSH terms: Neuronal Ceroid-Lipofuscinoses
Study type: Interventional
Phase: Phase 1/Phase 2

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 description: 
      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.
    

Intervention name(s): AAVrh.10CUCLN2
Intervention type(s): Biological
Intervention description(s): There will be 2 dose cohorts in this study. Group A consists of 2 subjects who have received 9.0x10^11 genome copies (900,000,000,000 molecules) of the study drug, AAVrh.10CUCLN2. Group B will consist of 6 subjects who will receive a lower dose of 2.85x10^11 genome copies (285,000,000,000 molecules) of the study drug, AAVrh.10CUCLN2.
Other intervention name(s): AAVrh.10
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Batten Disease