A Phase 1/2 Randomized, Blinded, Dose-escalation Study to Evaluate the Safety and Efficacy of Intrathecal Administration of AAV9-ABCD1 Gene Therapy (SBT101) in Adult Patients With Adrenomyeloneuropathy
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- AMN
- Sponsor
- SwanBio Therapeutics, Inc.
- Enrollment
- 8
- Locations
- 2
- Primary Endpoint
- Adverse Events to SBT101
- Status
- Terminated
- Last Updated
- 6 months ago
Overview
Brief Summary
This is a Phase 1/2 randomized, blinded, dose-escalation study to evaluate the safety and efficacy of intrathecal (IT) administration of SBT101, a recombinant adeno-associated virus serotype 9 (AAV9) containing a functional copy of the human adenosine triphosphate (ATP)-binding cassette transporter subfamily D member 1 (ABCD1; hABCD1) gene, in adult patients with adrenomyeloneuropathy (AMN) aged 18-65 years.
Patients will receive a single dose of SBT101 via IT route (or an imitation procedure) and will be followed for safety and efficacy for 2 years. Patients receiving SBT101 will be followed for an additional 3 years (5 total) for Safety. Patients receiving an imitation procedure will be offered the opportunity to receive SBT101 after 2 years, as data indicate.
Detailed Description
The study consists of two parts after infusion of SBT101: Part 1: A blinded 24-month core study period to evaluate the safety and potential impact of SBT101 on disease progression. Part 1 will consist of 2 phases: Phase 1: Dose-Escalation Phase: Two (2) doses of SBT101 (Dose level 1 cohort and Dose Level 2 cohort) will be evaluated to establish the maximum tolerated dose (MTD). Phase 2: Dose-Expansion Phase: Additional patients will be enrolled to receive SBT101 at the MTD Part 2: An unblinded 3-year long-term safety follow-up period with annual follow-up visits to evaluate the safety of SBT101 and disease progression.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosed with X-linked adrenoleukodystrophy (ALD), including proven mutation in the ABCD1 gene through confirmatory genetic testing, and supported by elevated circulating VLCFA levels.
- •Clinical evidence of spinal cord involvement but still able to ambulate independently
Exclusion Criteria
- •Evidence of or past diagnosis of inflammatory cerebral disease.
- •15 years or more have elapsed since the initial onset of myeloneuropathy manifestations such as walking or running difficulties, bladder dysfunction, increased muscular tone, spasticity, weakness, balance problems, etc.
- •Contraindications for MRI procedure and/or contrast materials.
- •Contraindication to steroids, sirolimus, tacrolimus, and/or anesthetic medications.
- •Unstable adrenal function (e.g., untreated or inappropriately treated adrenal insufficiency).
- •History of diabetes or abnormal fasting plasma glucose (≥126 mg/dL) or hemoglobin A1C ≥6.5%.
- •Patients who have received a gene therapy.
Outcomes
Primary Outcomes
Adverse Events to SBT101
Time Frame: 2 years
Safety and tolerability of SBT101 administration
Secondary Outcomes
- Disease progression(2 years)