A Study of AAV9 Gene Therapy in Participants With Canavan Disease (CANaspire Clinical Trial)

Phase 1

Recruiting

• Conditions: Canavan Disease
• Interventions: Biological: AAV9 BBP-812

• Registration Number: NCT04998396
• Lead Sponsor: Aspa Therapeutics

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.

Study Timeline

• Study First Submitted: 2021-08-05
• Study First Submitted QC: 2021-08-09
• Study First Posted: 2021-08-10
• Study Start: 2021-09-08
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-21
• Last Update Posted: 2024-10-22
• Primary Completion: 2026-10-13
• Study Completion: 2030-10-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 26

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose-Finding Phase: BBP-812 Dose Level 2 (Cohort 2)	AAV9 BBP-812	Participants will receive a single IV infusion of high-dose BBP-812 on Day 0 in the dose-finding phase of the study.
Dose-Finding Phase: BBP-812 Dose Level 1 (Cohort 1)	AAV9 BBP-812	Participants will receive a single intravenous (IV) infusion of low-dose BBP-812 on Day 0 in the dose-finding phase of the study.
Enrollment Expansion Phase: BBP-812	AAV9 BBP-812	Participants will receive a single IV infusion of BBP-812 at the selected dose from the dose-finding phase on Day 0 in expansion phase of the study.

Primary Outcome Measures

Name	Time	Method
Change from Baseline to 12 Months Post-Infusion in Urine N-acetylaspartate (NAA) Levels	Baseline, Month 12
Number of Participants with Adverse Events (AEs)	Baseline up to Week 52
Change from Baseline to 12 Months Post-Infusion in Central Nervous System (CNS) NAA, as Measured by Magnetic Resonance Spectroscopy (MRS)	Baseline, Month 12

Secondary Outcome Measures

Name	Time	Method
Change from Baseline to Week 52 in Adaptive Function, Vineland-3	Baseline, Week 52
Change from Baseline to Week 52 in Gross Motor Assessment, Gross Motor Function Measure-88	Baseline, Week 52
Change from Baseline to Week 52 in Cognitive Assessment, Bayley-4	Baseline, Week 52
Change from Baseline to Week 52 in Fine Motor Assessment, Bayley-4	Baseline, Week 52
Change from Baseline to Week 52 in Communication Assessment, Bayley-4	Baseline, Week 52

Trial Locations

Locations (4)

Massachusetts General Hospital (MGH); Center for Rare Neurological Diseases (CRND); 🇺🇸 Boston, Massachusetts, United States

Ann & Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Weill Cornell Medicine; Division of Pediatric Neurology; 🇺🇸 New York, New York, United States

UCSF Benioff Children's Hospital Oakland; 🇺🇸 Oakland, California, United States