ENROLLING_BY_INVITATION

rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Canavan Disease is a congenital white matter disorder caused by mutations to the gene encoding for aspartoacylase (ASPA). Expression of ASPA is restricted to oligodendrocytes, the sole white matter producing lineage in the brain. ASPA supports myelination in the capacity of its sole known function, namely, the catabolism of N-acetylaspartate (NAA). Inherited mutations that result in loss of ASPA catabolic activity result in a typically severe phenotype of Canavan Disease, characterized by chronically elevated brain NAA, gross motor abnormalities, hypomyelination, progressive spongiform degeneration of the brain, epilepsy, blindness, and a short life expectancy. Disease severity is correlated with residual levels of enzyme activity. Reconstitution of ASPA function in oligodendrocytes of the brains of Canavan patients is expected to rescue NAA metabolism in its natural cellular compartment and support myelination/remyelination by resident white matter producing cells. This protocol directly targets oligodendrocytes in the brain, which are intimately involved with disease initiation and progression. Targeting oligodendrocytes offers the safest and most direct therapy for affected individuals. The latest generation AAV viral vector (rAAV-Olig001-ASPA) will be administered to patients using neurosurgical procedure which involves direct administration of gene therapy to affected regions of the brain. Outcome measures for the open label clinical trial include longitudinal clinical assessments and brain imaging. Currently, there is no effective treatment for Canavan Disease. The purpose of this study is to validate a new technology targeted to the cells most affected by Canavan Disease in the safest way possible. The study investigators are committed to supporting the Rare Disease \& Canavan Disease Communities. For more information, please contact Jordana Holovach, Head of Communications and Community at PatientAdvocacy@myrtellegtx.com.

Official Title

Phase 1/2, Open Label, Sequential Cohort Study of a Single Intracranial Dose of AVASPA Gene Therapy for Treatment of Children With Typical Canavan Disease

Quick Facts

Study Start:2021-04-01
Study Completion:2027-08-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ENROLLING_BY_INVITATION

Study ID

NCT04833907

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:3 Months to 60 Months
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD
Inclusion CriteriaExclusion Criteria
  1. * Definitive diagnosis of typical CD by a board certified neurologist.
  2. * Written informed consent from parent(s)/guardian(s). Consent to enroll into the study will include a written agreement to comply with all the conditions of the study, including attendance at follow-up visits.
  3. * For cohort 1: age more than 36 months and up to 60 months.
  4. * For cohort 2: age between 15 months and 36 months.
  5. * For cohort 3: age less than 15 months.
  1. * At the discretion of the PI, any significant chronic medical condition, including, but not limited to neurological, cardiac, hepatic, renal, hematological, gastrointestinal, endocrine, pulmonary, or infectious disease, which would put the subject at increased risk during surgery or which would interfere with participation in the study, interpretation of safety monitoring, or the integrity of the study data.
  2. * History of severe allergic reaction or anaphylaxis.
  3. * Past participation in gene therapy trials or receipt of any other investigational product within 6 months prior to enrollment.
  4. * Prior intracranial surgery.
  5. * Any absolute contraindication to immunosuppression.
  6. * Any absolute contraindication to MRI.
  7. * Any vaccination less than 1 month prior to gene therapy.
  8. * Anticipated life expectancy of less than 12 months for any reason.
  9. * GMFM-88 total raw score \>35%.
  10. * Clinically significant out-of-range lab values, at the discretion of clinical PI.

Contacts and Locations

Principal Investigator

Robert Lober, MD, PhD
PRINCIPAL_INVESTIGATOR
Dayton Children's Hospital

Study Locations (Sites)

Dayton Children's Hospital
Dayton, Ohio, 45404
United States

Collaborators and Investigators

Sponsor: Myrtelle Inc.

  • Robert Lober, MD, PhD, PRINCIPAL_INVESTIGATOR, Dayton Children's Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-04-01
Study Completion Date2027-08-31

Study Record Updates

Study Start Date2021-04-01
Study Completion Date2027-08-31

Terms related to this study

Keywords Provided by Researchers

  • Canavan Disease
  • Gene Therapy
  • Aspartoacylase
  • N-Acetyl-Aspartate
  • Oligodendrocyte
  • Leukodystrophy
  • Adeno-Associated Virus Vector
  • Autosomal Recessive Disorder
  • Neurodegenerative
  • White Matter Disorder

Additional Relevant MeSH Terms

  • Canavan Disease