Back to resultsA Study of AAV9 Gene Therapy in Participants With Canavan Disease (CANaspire)
Primary Purpose
Canavan Disease
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AAV9 BBP-812
Sponsored by
About this trial
This is an interventional treatment trial for Canavan Disease focused on measuring 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
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
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
Sites / Locations
- UCSF Benioff Children's Hospital OaklandRecruiting
- Ann & Robert H. Lurie Children's Hospital of Chicago
- Massachusetts General Hospital (MGH); Center for Rare Neurological Diseases (CRND)Recruiting
- Weill Cornell Medicine; Division of Pediatric NeurologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Dose-Finding Phase: BBP-812 Dose Level 1 (Cohort 1)
Dose-Finding Phase: BBP-812 Dose Level 2 (Cohort 2)
Enrollment Expansion Phase: BBP-812
Arm Description
Participants will receive a single intravenous (IV) infusion of low-dose BBP-812 on Day 0 in the dose-finding phase of the study.
Participants will receive a single IV infusion of high-dose BBP-812 on Day 0 in the dose-finding phase of the study.
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.
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events (AEs)
Change from Baseline to 12 Months Post-Infusion in Urine N-acetylaspartate (NAA) Levels
Change from Baseline to 12 Months Post-Infusion in Central Nervous System (CNS) NAA, as Measured by Magnetic Resonance Spectroscopy (MRS)
Secondary Outcome Measures
Change from Baseline to Week 52 in Gross Motor Assessment, Gross Motor Function Measure-88
Change from Baseline to Week 52 in Fine Motor Assessment, Bayley-4
Change from Baseline to Week 52 in Cognitive Assessment, Bayley-4
Change from Baseline to Week 52 in Communication Assessment, Bayley-4
Change from Baseline to Week 52 in Adaptive Function, Vineland-3
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04998396
Brief Title
A Study of AAV9 Gene Therapy in Participants With Canavan Disease
Acronym
CANaspire
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 8, 2021 (Actual)
Primary Completion Date
October 15, 2024 (Anticipated)
Study Completion Date
March 15, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aspa Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose-Finding Phase: BBP-812 Dose Level 1 (Cohort 1)
Arm Type
Experimental
Arm Description
Participants will receive a single intravenous (IV) infusion of low-dose BBP-812 on Day 0 in the dose-finding phase of the study.
Arm Title
Dose-Finding Phase: BBP-812 Dose Level 2 (Cohort 2)
Arm Type
Experimental
Arm Description
Participants will receive a single IV infusion of high-dose BBP-812 on Day 0 in the dose-finding phase of the study.
Arm Title
Enrollment Expansion Phase: BBP-812
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
AAV9 BBP-812
Intervention Description
Sterile solution for injection for 1-time use via volumetric infusion pump
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs)
Time Frame
Baseline up to Week 52
Title
Change from Baseline to 12 Months Post-Infusion in Urine N-acetylaspartate (NAA) Levels
Time Frame
Baseline, Month 12
Title
Change from Baseline to 12 Months Post-Infusion in Central Nervous System (CNS) NAA, as Measured by Magnetic Resonance Spectroscopy (MRS)
Time Frame
Baseline, Month 12
Secondary Outcome Measure Information:
Title
Change from Baseline to Week 52 in Gross Motor Assessment, Gross Motor Function Measure-88
Time Frame
Baseline, Week 52
Title
Change from Baseline to Week 52 in Fine Motor Assessment, Bayley-4
Time Frame
Baseline, Week 52
Title
Change from Baseline to Week 52 in Cognitive Assessment, Bayley-4
Time Frame
Baseline, Week 52
Title
Change from Baseline to Week 52 in Communication Assessment, Bayley-4
Time Frame
Baseline, Week 52
Title
Change from Baseline to Week 52 in Adaptive Function, Vineland-3
Time Frame
Baseline, Week 52
10. Eligibility
Sex
All
Maximum Age & Unit of Time
30 Months
Accepts Healthy Volunteers
No
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michelle Nelken
Phone
833-764-2267 or 617-861-4617
Email
CANaspire@aspatx.com
First Name & Middle Initial & Last Name or Official Title & Degree
clinicaltrials@aspatx.com
Facility Information:
Facility Name
UCSF Benioff Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marissa Evans
Phone
510-428-3885
Ext
5421
Email
Marissa.Evans@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Annie Salko
Phone
510-428-3885
Ext
7217
Email
Annie.Sako@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Alexander Fay, MD
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra (Ally) Byrd
Phone
312-227-0067
Email
albyrd@luriechildrens.org
First Name & Middle Initial & Last Name & Degree
Jennifer Rubin, MD
Facility Name
Massachusetts General Hospital (MGH); Center for Rare Neurological Diseases (CRND)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lizbeth De la Rosa Abreu
Phone
617-724-1330
Email
ldelarosaabreu@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Ellen Winter
Phone
781-424-4137
Email
ewinter1@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Florian Eichler, MD
Facility Name
Weill Cornell Medicine; Division of Pediatric Neurology
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amelia Stone
Phone
212-746-3280
Email
Aks4017@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Zuhal Ergonul, MD PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://aspatx.com
Description
Aspa Therapeutics Company Website
URL
http://treatcanavan.com
Description
Canavan Disease Program Website
Learn more about this trial
A Study of AAV9 Gene Therapy in Participants With Canavan Disease
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