| Eligibility |
Inclusion Criteria:
1. Able to give informed consent before any assessment is performed.
2. Adult males aged 18 or greater with a confirmed genetic diagnosis (confirmed CAG
repeat expansion in the AR gene of at least 36 repeat) of SBMA and clinical diagnosis
of symptomatic muscle weakness.
3. Able to complete 2MWT with or without the aid of an assisted device at screening.
4. SBMAFRS score =26 (subjects with moderate to high physical performance) at screening.
5. Willing to participate in all aspects of study design and assessments, including blood
draw and muscle biopsies.
6. Male subjects and their female spouses/partners who are of childbearing potential must
agree to use highly effective contraception consisting of 2 forms of birth control (at
least 1 of which must be a barrier method) starting from the first dose of the study
drug and continuing throughout the study period and for 90 days after the last dose of
the study drug. Male subjects should also not donate sperm during the study and for 90
days after the final administration of the study drug.
7. Able to communicate well with the Investigator, to understand, and comply with the
requirements of the study.
Exclusion Criteria:
1. Nonambulatory.
2. Contraindications to MRI such as a contraindicated nonremovable metal device (ie,
pacemaker, defibrillator, insulin pump, metal clips, nonremovable jewelry) or
claustrophobia.
3. Use of other investigational products within 30 days, or within 5 half-lives,
whichever is longer, prior to the first dosing, or until the expected PD effect has
returned to baseline, whichever is longer. Approved COVID-19 vaccines are not
considered investigational treatments and are allowed prior to, during, and after the
study.
4. Use of drugs known to affect muscle metabolism within the previous 1 month prior to
the first dosing, including (but not limited to) systemic corticosteroids (>10 mg/day
prednisone or equivalent), androgens, or androgen reducing agents, systemic beta
agonists or beta blockers, and relevant herbal, or nutraceutical products. For
subjects using systemic corticosteroids (=10 mg/day or equivalent), they should be on
stable dose for the previous 3 months prior to first dosing.
5. Known history of allergic reactions to curcumin analogs or excipients in the study
drug formulation.
6. Known history of clinically significant cardiovascular disease (including uncontrolled
hypertension, ischemic heart disease [eg, myocardial infarction, angina, abnormal
coronary arteriography or cardiac stress testing/imaging]), heart failure or left
ventricle dysfunction of New York Heart Association Classification III-IV, or
clinically significant cerebrovascular disease (stroke or transient ischemic attacks).
7. An abnormal ECG at screening visit which is judged to be clinically relevant and
represents an unacceptable risk for study participation by the Investigator. An
example is Brugada-like ECG changes which have been reported in SBMA patients in Italy
and Japan.
8. Any surgical or medical condition which may jeopardize the subject in case of
participation in the study. The Investigator should make this determination in
consideration of the subject's medical history and/or clinical or laboratory evidence
of any of the following during screening:
1. Liver disease or liver injury as indicated by abnormal liver function tests such
as AST, ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), or
serum bilirubin in the presence of normal serum creatine kinase (CK).
2. Significant swallowing dysfunction, which may increase the risk of accidental
choking and aspiration pneumonia.
9. Subjects with renal impairment defined as a creatinine clearance of <90 mL/min at
screening. (Creatinine Clearance = [140 - age in years] *weight in kg]/[72*serum
Cr(mg/dL)]).
10. History of active tuberculosis or exposure to endemic areas within 8 weeks prior to
QuantiFERON®-TB testing performed at screening.
11. Positive QuantiFERON®-TB indicating possible tuberculosis infection.
12. History of immunodeficiency diseases, including a positive HIV test result at
screening.
13. A positive hepatitis B surface antigen or hepatitis C test result at screening.
14. Subjects with known bleeding disorders, or who are under treatment with anticoagulants
or with a platelet count <50,000 (due to the increased risk of bleeding during muscle
biopsy procedure).
15. History of drug or alcohol abuse within the 12 months prior to the first dosing, or
evidence of such abuse as indicated by the laboratory assays conducted during
screening.
16. The Investigator should be guided by the following criteria during screening: a. Any
single laboratory parameter may not exceed 3 times the upper limit of normal (ULN). A
single parameter elevated up to and including 3 times the ULN should be re-checked
once more as soon as possible, and in all cases, at least prior to
enrollment/randomization, to rule out lab error. For abnormal liver function tests, in
the presence of elevated serum CK levels, ALT, or AST, up to 5 times the ULN are
acceptable if other liver tests are normal. b. If the total bilirubin concentration is
increased above 1.5 times the ULN, total bilirubin should be differentiated into the
direct and indirect reacting bilirubin. In any case, serum indirect bilirubin should
not exceed the value of 1.6 mg/dL (27 mol/L).
17. Use of drugs that are inhibitors of CYP3A4, 2B6, or 2C19 within 2 weeks prior to the
first dosing and during the study.
18. Use of drugs that are substrates of MATE1 or MATE2-K transporters within 2 weeks prior
to the first dosing and during the study.
19. Use of turmeric or products containing curcumin within 2 weeks prior to the first
dosing and during the study.
20. Use of aspirin or nonsteroidal anti-inflammatory agents within 3 days prior to the
baseline visit (due to the increased risk of bleeding during muscle biopsy procedure).
21. Any reason that, in the opinion of the Investigator, would prevent the subject from
participating in the study.
|
