Clinical trial NCT05394064: A Study to Evaluate Administration of SBT101 Gene Therapy in Adult Patients With Adrenomyeloneuropathy (AMN)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: AMN
AMN Gene Mutation
X-ALD
Keywords: 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
Lead sponsor: SwanBio Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-27
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3 Cohorts, each with active treatment and 1 with imitation procedure
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Events to SBT101
timeFrame: 2 years
Secondary outcomes:
measure: Disease progression
timeFrame: 2 years
Other outcomes:
measure: Change in Quality of Life
timeFrame: 2 years
Locations:
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
References: