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

NCT05517603 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: JM17-201-201
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 6

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).

Conditions

Spinal and Bulbar Muscular Atrophy; Kennedy's Disease

Outcome Measures

Primary Outcomes (1)

• Incidence and proportion of subjects with AEs including SAEs and TEAEs.

  Safety will be monitored throughout the study.

  12 weeks

Secondary Outcomes (3)

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) will be assessed

  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.

• Pharmacokinetics: Area Under the Curve (AUC) will be assessed

  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.

• Pharmacodynamics: Change from baseline in mutant androgen receptor protein levels in skeletal muscle in treatment vs placebo group.

  Visit 2/Week 1 and Visit 5/Week 12

Study Arms (2)

Experimental: AJ201

ACTIVE COMPARATOR

Subjects taking active drug AJ201 600mg/day for 12 weeks.

Drug: AJ201

Placebo Comparator

PLACEBO COMPARATOR

Subjects taking placebo for 12 weeks.

Drug: Placebo

Interventions

AJ201 DRUG

Administered orally

Also known as: JM17

Experimental: AJ201

Placebo DRUG

Administered orally

Placebo Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give informed consent before any assessment is performed.
• 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.
• Able to complete 2MWT with or without the aid of an assisted device at screening.
• SBMAFRS score ≥26 (subjects with moderate to high physical performance) at screening.
• Willing to participate in all aspects of study design and assessments, including blood draw and muscle biopsies.
• 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.
• Able to communicate well with the Investigator, to understand, and comply with the requirements of the study.

You may not qualify if:

• Nonambulatory.
• Contraindications to MRI such as a contraindicated nonremovable metal device (ie, pacemaker, defibrillator, insulin pump, metal clips, nonremovable jewelry) or claustrophobia.
• 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.
• 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.
• Known history of allergic reactions to curcumin analogs or excipients in the study drug formulation.
• 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).
• 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.
• 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:
• 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).
• Significant swallowing dysfunction, which may increase the risk of accidental choking and aspiration pneumonia.
• Subjects with renal impairment defined as a creatinine clearance of \<90 mL/min at screening. (Creatinine Clearance = \[140 - age in years\] \*weight in kg\]/\[72\*serum Cr(mg/dL)\]).
• History of active tuberculosis or exposure to endemic areas within 8 weeks prior to QuantiFERON®-TB testing performed at screening.
• Positive QuantiFERON®-TB indicating possible tuberculosis infection.
• History of immunodeficiency diseases, including a positive HIV test result at screening.
• A positive hepatitis B surface antigen or hepatitis C test result at screening.

Sponsors & Collaborators

• AnnJi Pharmaceutical Co., Ltd.: lead

Study Sites (6)

University of California, Irvine

Orange, California, 92868, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

National Institutes of Health

Bethesda, Maryland, 20814, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Bulbo-Spinal Atrophy, X-Linked

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: August 26, 2022
• Study Start: February 28, 2023
• Primary Completion: April 8, 2024
• Study Completion: April 8, 2024
• Last Updated: August 15, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)