AMN, AMN Gene Mutation, X-ALD
Conditions
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
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.
Interventions
GENETICSBT101 Treatment
SBT101 Treatment
Sponsors
SwanBio Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Maintain masking to all but those are perform the actual procedure
Intervention model description
2 Cohorts, each with active treatment
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events to SBT101. Any Serious TEAE. Any Serious TEAE Related to the Study Procedure or Study Drug. | 2 years | 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. |
Countries
Netherlands, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Adrenal Insufficiency No | 3 Participants |
| Adrenal Insufficiency Yes | 3 Participants |
| Age, Continuous | 28.3 Years STANDARD_DEVIATION 7.41 |
| Baseline EDSS | 3.06 Score on a scale STANDARD_DEVIATION 0.729 |
| Confirmed Mutation in the ABCD1 Gene | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
| Time Since AMN Diagnosis | 2.14 Years STANDARD_DEVIATION 1.333 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 | 2 / 4 |
Outcome results
None listed