NCT01414985

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

Completed Phase 1, PHASE2 Last updated 31 August 2020

What this trial tests

Phase 1, PHASE2 trial testing AAVrh.10CUCLN2 in Late Infantile Neuronal Ceroid Lipofuscinosis in 8 participants. Completed in 8 February 2017.

Timeline

15 April 2010

Primary endpoint
30 November 2015

8 February 2017

Quick facts

Lead sponsor	Weill Medical College of Cornell University
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	8
Start date	15 April 2010
Primary completion	30 November 2015
Estimated completion	8 February 2017
Sites	1 location across United States

Drugs / interventions tested

• AAVrh.10CUCLN2 — full drug profile →

Conditions studied

• Late Infantile Neuronal Ceroid Lipofuscinosis — all drugs for Late Infantile Neuronal Ceroid Lipofuscinosis →
• Batten Disease — all drugs for Batten Disease →

Sponsor

Weill Medical College of Cornell University

Who can join

Adults 3 to 18, any sex, with Late Infantile Neuronal Ceroid Lipofuscinosis or Batten Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Viral vector platforms within the gene therapy landscape.
   Bulcha JT, Wang Y, Ma H, Tai PWL, et al · · 2021 · cited 899× · PMID 33558455 · DOI 10.1038/s41392-021-00487-6
2. Current Clinical Applications of In Vivo Gene Therapy with AAVs.
   Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, Goodspeed K, et al · · 2021 · cited 544× · PMID 33309881 · DOI 10.1016/j.ymthe.2020.12.007
3. Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality.
   Hudry E, Vandenberghe LH. · · 2019 · cited 263× · PMID 30844402 · DOI 10.1016/j.neuron.2019.02.017
4. Recombinant Adeno-Associated Virus Gene Therapy in Light of Luxturna (and Zolgensma and Glybera): Where Are We, and How Did We Get Here?
   Keeler AM, Flotte TR. · · 2019 · cited 247× · PMID 31283441 · DOI 10.1146/annurev-virology-092818-015530
5. The baculovirus expression vector system: A commercial manufacturing platform for viral vaccines and gene therapy vectors.
   Felberbaum RS. · · 2015 · cited 173× · PMID 25800821 · DOI 10.1002/biot.201400438
6. Clinical trials in rare disease: challenges and opportunities.
   Augustine EF, Adams HR, Mink JW. · · 2013 · cited 165× · PMID 24014509 · DOI 10.1177/0883073813495959
7. Viral vectors for therapy of neurologic diseases.
   Choudhury SR, Hudry E, Maguire CA, Sena-Esteves M, et al · · 2017 · cited 143× · PMID 26905292 · DOI 10.1016/j.neuropharm.2016.02.013
8. Gene therapy for neurodegenerative disorders: advances, insights and prospects.
   Chen W, Hu Y, Ju D. · · 2020 · cited 114× · PMID 32963936 · DOI 10.1016/j.apsb.2020.01.015