A Study to Evaluate the Safety and Tolerability of Intravenous Stemis™ in Elderly Subjects With Mild to Moderate Frailty Syndrome

Official title

A Phase 1, Randomized, Double-blind, Placebo-controlled, Dose-Escalation Study to Evaluate the Safety and Tolerability of Stemis™ Administered Intravenously in Elderly Subjects With Mild to Moderate Frailty Syndrome

Overview

This is a Phase 1 clinical study designed to evaluate the safety and tolerability of an investigational cell therapy product, Stemis™, in older adults with mild to moderate frailty. Frailty is a condition commonly seen in older adults and may include decreased strength, slower walking speed, and reduced ability to perform daily activities. Currently, there is no specific drug treatment approved for frailty. Stemis™ is an investigational product made from human umbilical cord-derived mesenchymal stem cells. This product has been evaluated for safety in nonclinical studies and in clinical studies for other conditions. Approximately 12 participants between 60 and 85 years of age who have been assessed as having mild to moderate frailty will take part in this study. Participants will be randomly assigned to receive either Stemis™ or a placebo (saltwater solution). The study is double-blind, meaning that neither the participants nor the study staff will know which treatment is given. The study treatment will be administered by intravenous infusion. During the study, participants will be closely monitored for safety, including the occurrence of adverse events, vital signs, laboratory tests, and physical examinations. In addition, assessments such as walking ability, hand grip strength, and quality-of-life questionnaires will be performed as exploratory measures. This study is not intended to provide direct medical benefit to participants. The primary purpose of the study is to collect safety information to support future clinical research.

Interventions

• Biological Stemis™
  Stemis™ is an investigational cell therapy product administered by intravenous infusion. Participants assigned to this intervention will receive multiple administrations of Stemis™. The dosing frequency and administration schedule differ by cohort, and safety monitoring is conducted throughout the study.
• Drug Normal Saline
  Normal Saline

Primary outcome measures

• Determination of the Maximum Feasible Dose (MFD) of Stemis™ based on the occurrence of Dose-Limiting Toxicities (DLTs) [Time frame: From first dose (Day 1) through 26 weeks after the last dose]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: From first administration of study intervention through 26 weeks after the last dose]
• Incidence of withdrawals due to adverse events (AEs) [Time frame: From first administration of study intervention through 26 weeks after the last dose]
• Number of Participants with Clinically Significant Changes in Physical Examination Findings [Time frame: From first administration of study intervention through 26 weeks after the last dose]
• Number of Participants with Clinically Significant Changes in Clinical Laboratory Test Results [Time frame: From first administration of study intervention through 26 weeks after the last dose]
• Number of Participants with Clinically Significant Changes in Vital Signs [Time frame: From first administration of study intervention through 26 weeks after the last dose]

Secondary outcome measures (10)

• Six-Minute Walk Test (6MWT) [Time frame: From baseline through 26 weeks after the last dose]
• Hand Grip Strength - maximum force [Time frame: From baseline through 26 weeks after the last dose]
• Short Physical Performance Battery (SPPB) - total score [Time frame: From baseline through 26 weeks after the last dose]
• Clinical Frailty Scale (CFS) - score [Time frame: From baseline through 26 weeks after the last dose]
• Falls Efficacy Scale-International (FES-I) - total score [Time frame: From baseline through 26 weeks after the last dose]
• PROMIS Physical Function Short Form 20a - T-score [Time frame: From baseline through 26 weeks after the last dose]
• World Health Organization Quality of Life-BREF (WHOQOL-BREF) - domain scores [Time frame: From baseline through 26 weeks after the last dose]
• 12-Item Short Form Health Survey (SF-12) - Physical and Mental Component Summary scores [Time frame: From baseline through 26 weeks after the last dose]
• Creatine Phosphokinase (CPK) [Time frame: From baseline through 26 weeks after the last dose]
• N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) [Time frame: From baseline through 26 weeks after the last dose]

Eligibility criteria

Inclusion criteria

Subjects will be eligible for enrollment in the study only if they meet all the following criteria at time of Screening:

• Subjects aged ≥ 60 through ≤ 85 years old.
• Subjects with clinical diagnosis of mild to moderate FS as assessed by the Investigator with a CFS score between 4 to 6.
• Subjects will not start any new treatment for this condition during the study.
• Subjects with body weight between 40 to 90 kg.
• Subjects are willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided.

Exclusion criteria

Subjects meeting any of the following criteria at time of Screening will be excluded from enrollment:

• Subjects unwilling or unable to perform any of the assessments required by endpoint analysis.
• Subjects who have a diagnosis of any disabling neurologic disorder including, but not limited to: Parkinson's disease, Amyotrophic Lateral Sclerosis, multiple sclerosis, stroke or dementia.
• Subjects who have a score on the Mini-Mental State Examination (MMSE) of 24 or below.
• Subjects who have a significant comorbid medical condition(s) including, but not limited to:

• Severe kidney disease requiring hemodialysis or peritoneal dialysis.
• Advanced liver diseases such as severe liver cirrhosis.
• Severe congestive heart failure (NYHA class 3 and 4).
• Severe pulmonary dysfunction, including severe chronic obstructive pulmonary disease stage III or IV (Gold classification)
• Subjects who have a history of deep venous thrombosis or pulmonary embolism, known hypercoagulability, or known family history of thromboembolic disease.
• Subjects who have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively treated basal cell carcinoma or in situ carcinomas.
• Subjects using chronic immunosuppressant therapy, including corticosteroids (> 5 mg/day of prednisone, or equivalent), or TNF-alpha antagonists.
• Subjects on chronic immunosuppressive transplant therapy.
• Subjects who have participated in another clinical study of new investigational therapies within 6 months prior to screening.
• Subjects who have received any other stem cell therapy within 12 months prior to screening.
• Subjects with known allergies or hypersensitivity to any component of the formulation and cellular therapies (i.e., penicillin or streptomycin).
• Subjects who have a history of drug or alcohol abuse within the past 3 years.
• Subjects who are known to be infected with Human Immunodeficiency Virus (HIV).
• Subjects are currently hospitalized.
• Subjects who have a significant illness as judged by principal investigator (PI) including, but not limited to:

• Psychiatric illness
• Uncontrolled hypertension or hypotension
• Unstable cardiac arrhythmia
• Active Hepatitis B, Hepatitis C infections
• Subjects who have any condition that in the opinion of the PI limits lifespan to < 1 year.
• Subjects who have any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.

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Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• Taipei Medical University Hospital — Taipei

Identifiers

NCT: NCT07462819 · JY-STEMIS-007

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗