Clinical trial NCT04998396: A Study of AAV9 Gene Therapy in Participants With Canavan Disease (CANaspire Clinical Trial)
Official title: A Phase 1/2 Open-Label Study of the Safety and Clinical Activity of Gene Therapy for Canavan Disease Through Administration of an Adeno-Associated Virus (AAV) Serotype 9-Based Recombinant Vector Encoding the Human ASPA Gene
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Canavan Disease
Keywords: Canavan Disease
AAV
AAV9
Gene therapy
Aspartoacylase
ASPA
ASPA gene
rAAV9
ACY2
Aminoacylase 2
Spongy degeneration
N-acetyl-L-aspartic acid (NAA)
N-acetylaspartate
Rare disease
Inherited Metabolic Disorders
Leukodystrophy
Leukoencephalopathies
Autosomal Recessive Disorder
Neurodevelopmental diseases
CANaspire Clinical Trial
Lead sponsor: Aspa Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-08-10
Enrollment: 26
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The main objective of this trial is to evaluate the safety, tolerability, and pharmacodynamic activity of BBP-812, an investigational AAV9-based gene therapy, in pediatric participants with Canavan disease.

Detailed description: Canavan disease is an ultra-rare, profoundly disabling and fatal disease with no approved therapy. The Sponsor is developing BBP-812, an investigational gene therapy product for systemic delivery in participants with Canavan disease. BBP-812 is a recombinant adeno-associated virus serotype 9 (rAAV9) vector engineered to deliver the aspartoacylase (ASPA) transgene under control of a ubiquitous promoter to restore ASPA expression in both neuronal and non-neuronal cell types.

Eligibility criteria: Key Inclusion Criteria:

* Maximum age for inclusion is 30 months.
* Participant has stable health in the opinion of the investigator and as confirmed by medical history and laboratory studies with no acute or chronic hematologic, renal, liver, immunologic, or neurologic disease (other than Canavan disease).
* Participant has biochemical, genetic, and clinical diagnosis of Canavan disease:

  * Elevated urinary NAA and
  * Biallelic mutation of the ASPA gene determined at Screening or documented in the participant's medical history.
  * Active clinical signs of Canavan disease
* Participant is up to date on all immunizations per local guidelines

Key Exclusion Criteria:

* Tests positive for total anti-AAV9 antibodies determined by enzyme-linked immunosorbent assay (ELISA).
* Received prior gene therapy or other therapy (including vaccines) involving AAV.
* Participant is receiving high-dose therapy with immunosuppressants.
* Participant has significantly progressed Canavan disease characterized as:

  * Presence of continuous/constant decerebrate or decorticate posturing,
  * Recurrent status epilepticus, or
  * Recalcitrant seizures that do not respond while on 3 or more anti-epileptic medications

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Baseline up to Week 52
measure: Change from Baseline to 12 Months Post-Infusion in Urine N-acetylaspartate (NAA) Levels
timeFrame: Baseline, Month 12
measure: Change from Baseline to 12 Months Post-Infusion in Central Nervous System (CNS) NAA, as Measured by Magnetic Resonance Spectroscopy (MRS)
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Change from Baseline to Week 52 in Gross Motor Assessment, Gross Motor Function Measure-88
timeFrame: Baseline, Week 52
measure: Change from Baseline to Week 52 in Fine Motor Assessment, Bayley-4
timeFrame: Baseline, Week 52
measure: Change from Baseline to Week 52 in Cognitive Assessment, Bayley-4
timeFrame: Baseline, Week 52
measure: Change from Baseline to Week 52 in Communication Assessment, Bayley-4
timeFrame: Baseline, Week 52
measure: Change from Baseline to Week 52 in Adaptive Function, Vineland-3
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH); Center for Rare Neurological Diseases (CRND)
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell Medicine; Division of Pediatric Neurology
state: New York
Study officials:
References: