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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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AMN, AMN Gene Mutation, X-ALD

Intervention / Treatment
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* Genetic: SBT101
* Procedure: Imitation Procedure


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3 Cohorts, each with active treatment and 1 with imitation procedure
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment<br>Patients treated with SBT101 | Genetic: SBT101<br>* SBT101 Treatment<br>|
| Sham Comparator: Imitation Procedure<br>Procedure that mimics treatment with SBT101, but does not infuse anything into the spinal cord | Procedure: Imitation Procedure<br>* Procedure that mimics SBT101 infusion, but contains no drug administered<br>* Other names: Sham Procedure;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events to SBT101 | Safety and tolerability of SBT101 administration | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression | Characterize disease progression in adults diagnosed with AMN through serial clinical assessments of walking ability measured by 6-Minute Walk Test | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMN, X-ALD, Adrenoleukodystrophy, X-linked Adrenoleukodystrophy, Adrenomyeloneuropathy, Myeloneuropathy, Spastic paraplegia, Hereditary Spastic Paraplegia, HSP, ALD, ABCD1, ALDP, CALD, CCALD, Brain Diseases, Metabolic, Inborn, Brain Diseases, Metabolic, Hereditary Central Nervous System Demyelinating Diseases, Leukoencephalopathies, Demyelinating Diseases, Heredodegenerative Disorders, Nervous System, Metabolism, Inborn Errors, Peroxisomal Disorders, Metabolic Diseases, Adrenal Insufficiency, Gene Therapy, AAV9, Adeno-Associated Vector