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

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

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.

Study Overview

• Status: Recruiting
• Conditions: AMN; AMN Gene Mutation; X-ALD
• Intervention / Treatment: Genetic: SBT101; Procedure: Imitation Procedure

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.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trial Recruitment; Phone Number: 267-417-6356; Email: clinicaltrials@swanbiotx.com

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Not yet recruiting
    • Amsterdam UMC
• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • University of Massachusetts Chan Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life	Characterize the change in multiple quality of life parameters over time using questionnaires including the Multiple Sclerosis Quality of Life-54 (MS-QOL)	2 years

Collaborators and Investigators

• Sponsor: SwanBio Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): March 30, 2029

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Gene Therapy; Adrenoleukodystrophy; X-linked Adrenoleukodystrophy; Metabolic Diseases; Metabolism, Inborn Errors; ALD; HSP; AAV9; Heredodegenerative Disorders, Nervous System; Leukoencephalopathies; Adrenomyeloneuropathy; Brain Diseases, Metabolic, Inborn; Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Hereditary Spastic Paraplegia; Brain Diseases, Metabolic; AMN; X-ALD; Myeloneuropathy; Spastic paraplegia; ABCD1; ALDP; CALD; CCALD; Hereditary Central Nervous System Demyelinating Diseases; Adeno-Associated Vector
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Leukoencephalopathies; Adrenal Gland Diseases; Hereditary Central Nervous System Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Adrenoleukodystrophy
• Other Study ID Numbers: SBT101-CT101; 2021-004410-19 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No