A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of AJ201 In Patients

• ClinicalTrials.gov Identifier: NCT05517603
• Recruitment Status: Recruiting
• First Posted: August 26, 2022
• Last Update Posted: August 7, 2023
• Sponsor: AnnJi Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): AnnJi Pharmaceutical Co., Ltd.

Study Description

Brief Summary:

This is a phase 1/2a randomized, double-blind study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of study drug AJ201 in subjects with Spinal and Bulbar Muscular Atrophy (SBMA).

Condition or disease	Intervention/treatment	Phase
Spinal and Bulbar Muscular Atrophy; Kennedy's Disease	Drug: AJ201; Drug: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2a, Randomized, Double-Blind, Placebo-Controlled, First-In-Patient Study Of AJ201 To Evaluate Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics In Adults With Spinal And Bulbar Muscular Atrophy (SBMA)
• Actual Study Start Date: February 28, 2023
• Estimated Primary Completion Date: September 30, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Experimental: AJ201; Subjects taking active drug AJ201 600mg/day for 12 weeks.	Drug: AJ201; Administered orally; Other Name: JM17
Placebo Comparator: Placebo Comparator; Subjects taking placebo for 12 weeks.	Drug: Placebo; Administered orally

Outcome Measures

Primary Outcome Measures :

1. Incidence and proportion of subjects with AEs including SAEs and TEAEs. [ Time Frame: 12 weeks ]
   Safety will be monitored throughout the study.

Secondary Outcome Measures :

1. Pharmacokinetics: Maximum Plasma Concentration (Cmax) will be assessed [ Time Frame: Visit 3/Week 2 and Visit 4/Week 6 at the following time points: predose and 0.5, 1, 2, 4, 8, and 12 hours postdose. ]
   Blood sampling will be collected at Visit 3 and Visit 4.
2. Pharmacokinetics: Area Under the Curve (AUC) will be assessed [ Time Frame: Visit 3/Week 2 and Visit 4/Week 6 at the following time points: predose and 0.5, 1, 2, 4, 8, and 12 hours postdose. ]
   Blood sampling will be collected at Visit 3 and Visit 4.
3. Pharmacodynamics: Change from baseline in mutant androgen receptor protein levels in skeletal muscle in treatment vs placebo group. [ Time Frame: Visit 2/Week 1 and Visit 5/Week 12 ]
   Samples will be collected at Visit 2 and Visit 5.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Andy Chen, PhD; +886-2-23655677; andy.chen@ajpharm.com

Locations

United States, California

University of California, Irvine; Recruiting

Orange, California, United States, 92868

Contact: Pola Gaid 714-456-6191 polagaid@hs.uci.edu

Principal Investigator: Tahseen Mozaffar, MD

Stanford University; Recruiting

Palo Alto, California, United States, 94304

Contact: Emily Lien 650-407-7912 emlien@stanford.edu

Principal Investigator: John Day, MD

United States, Florida

Mayo Clinic; Recruiting

Jacksonville, Florida, United States, 32224

Contact: Megan Donahue 904-953-3647 donahue.megan@mayo.edu

Principal Investigator: Bjorn Oskarsson, MD

United States, Maryland

National Institutes of Health; Recruiting

Bethesda, Maryland, United States, 20814

Contact: Angela Kokkinis 301-451-8146 akokkinis@cc.nih.gov

Principal Investigator: Christopher Grunseich, MD

United States, Minnesota

Mayo Clinic; Not yet recruiting

Rochester, Minnesota, United States, 55905

Contact: Jane L. Sultze 507-538-5523 sultze.jane@mayo.edu

Principal Investigator: Eric Sorenson, MD

United States, Missouri

Washington University in St. Louis; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Oliver Doerr 314-362-1626 oliver.doerr@wustl.edu

Contact: Jennifer Koniak (314) 362-1626 koniak@wustl.edu

Principal Investigator: Alan Pestronk, MD

Sponsors and Collaborators

AnnJi Pharmaceutical Co., Ltd.

More Information

• Responsible Party: AnnJi Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05517603
• Other Study ID Numbers: JM17-201-201
• First Posted: August 26, 2022
• Last Update Posted: August 7, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Atrophy; Bulbo-Spinal Atrophy, X-Linked; Atrophy; Pathological Conditions, Anatomical; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn