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: Adrenoleukodistrophy; degenerative neurological disease; 10029317

• Registration Number: NL-OMON56436
• Lead Sponsor: SwanBio Therapeutics, Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 5

Inclusion Criteria

1. Male adults aged >=18 and <= 65 years
2. Diagnosed with X-linked adrenoleukodystrophy (ALD)), including
proven mutation in the ABCD1 gene through confirmatory genetic
testing, and supported by historically elevated VLCFA.
3. Clinical evidence of spinal cord involvement with EDSS score between
1 and 4.5 and pyramidal function score of >=1 in the Functional System
Score of the EDSS. Signs of pyramidal tract dysfunction don't include
hyperreflexia.
4. Must agree to use reliable double-barrier contraception methods (e.g.,
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condom and 1 other form of contraception for female sexual partners
that are of childbearing potential, such as diaphragm, intrauterine
device, spermicidal jelly, and/or hormonal contraceptive) and to not
donate sperm for at least 6 months following the IMP procedure.
5. For patients who are receiving any other treatment for ALD, including
off-label medications and/or supplements (e.g., antioxidants, Lorenzo's
oil, statins, etc.) or physical rehabilitation support, such treatments must
have been at a stable dose and/or frequency for >=4 weeks prior to
Screening and patients must agree to continue at the same dose and/or
frequency through Part 1 of the study.
6. The patient provided written informed consent prior to any study
procedures being performed

Exclusion Criteria

1. Presence of inflammatory cerebral disease, established by
radiographic review of brain MRI demonstrating a Loes score >=0.5 on
the 34-point scale, except for the abnormalities that can be observed in
patients with AMN without inflammatory cerebral demyelination with
Loes score <=4.
2. Pathological changes identified on brain MRI including all lesions from
previous diagnosis of inflammatory cerebral disease with Loes score >=0.5 on the
34-point scale, except for the abnormalities that can be observed in patients
with AMN without inflammatory cerebral demyelination with Loes score <=4
3. 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.
4. Contraindications for MRI procedure and/or contrast materials.
5. History of a brain or spinal cord disease that would interfere with
lumbar puncture procedures, CSF circulation, and/or safety
assessments.
6. Contraindication to steroids, sirolimus, tacrolimus, and/or anesthetic
medications.
7. Contraindication to SBT101 and/or any of its ingredients.
8. Unstable adrenal function (e.g., untreated or inappropriately treated
adrenal insufficiency).
a. Adrenal function will be evaluated through laboratory assessments of
serum cortisol, plasma adrenocorticotropic hormone (ACTH), plasma
renin, aldosterone, sodium, and potassium levels at Screening.
Monitoring of replacement therapy will be mainly clinical. Determination
of inappropriately treated adrenal insufficiency will be made by the
Investigator in consultation with the Medical Monitor.
b. Patients who meet the following criteria will be considered to have
adrenal insufficiency: (i) basal cortisol concentration <275 nmol (10
µg/dL) in the morning (i.e., 6 AM to 10 AM) and (ii) plasma ACTH >= 2 ×
upper limit of normal (ULN).
9. Positive for human immunodeficiency virus (HIV) type 1 or 2 (HIV-1,
HIV-2), hepatitis B virus (HBV), or hepatitis C virus (HCV).
a. Patients who have been vaccinated against HBV (e.g., HBV surface
antibody-positive) who are negative for other markers of prior HBV
infection (e.g., HBV core antibody-negative) are eligible.
b. Patients who are positive for anti-HCV antibodies are eligible, as long
as they have a negative HCV load as measured by quantitative
polymerase chain reaction (qPCR).
10. Presence of a clinically significant active bacterial, viral, fungal,
parasitic, or prion-associated infection.
11. History of diabetes or abnormal fasting plasma glucose (>=126
mg/dL) or hemoglobin A1C >=6.5%.
12. Patients who have received a gene therapy.
13. Current use of medications that could potentially lead to changes in
intracranial pressure (e.g., levothyroxine, vitamin A supplementation,
oral contraceptives, tetracycline, acetazolamide [Diamox]).
14. Patients who are currently using strong CYP3A4 inducers or strong
CYP3A4 inhibitors, and are unwilling or unable to stop prior to and
during the immunosuppression regimen.
15. Patients who are currently receiving or have received an
investigational drug or procedure within 3 months prior to Screening.
The use of investigational drugs is prohibited throughout Part 1 of the
study.
16. Patients with unstable, clinically significant neurologic (other t

Study & Design

• Study Type: Interventional
• Study Design: Not specified