A Study to Evaluate Administration of SBT101 Gene Therapy in Adult Patients With Adrenomyeloneuropathy (AMN)

Phase 2TerminatedNCT05394064

SwanBio Therapeutics, Inc.9 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

AMN

Eligibility

Sex: MALEMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Diagnosed with X-linked adrenoleukodystrophy (ALD), including proven mutation in the ABCD1 gene through confirmatory genetic testing, and supported by elevated circulating VLCFA levels. 2. Clinical evidence of spinal cord involvement but still able to ambulate independently Exclusion Criteria: 1. Evidence of or past diagnosis of inflammatory cerebral disease. 2. 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. 3. Contraindications for MRI procedure and/or contrast materials. 4. Contraindication to steroids, sirolimus, tacrolimus, and/or anesthetic medications. 5. Unstable adrenal function (e.g., untreated or inappropriately treated adrenal insufficiency). 6. History of diabetes or abnormal fasting plasma glucose (≥126 mg/dL) or hemoglobin A1C ≥6.5%. 7. Patients who have received a gene therapy.

Outcomes

Primary Outcomes

Adverse Events to SBT101. Any Serious TEAE. Any Serious TEAE Related to the Study Procedure or Study Drug.

Any Treatment Emergent Adverse Event (TEAE). TEAE was defined as any adverse event which started during or after the administration of IMP or the immunosuppressant pre-medication.

Time frame: 2 years