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

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

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.

Inclusion Criteria:

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

1. Subjects aged ≥ 60 through ≤ 85 years old.
2. Subjects with clinical diagnosis of mild to moderate FS as assessed by the Investigator with a CFS score between 4 to 6.
3. Subjects will not start any new treatment for this condition during the study.
4. Subjects with body weight between 40 to 90 kg.
5. 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:

1. Subjects unwilling or unable to perform any of the assessments required by endpoint analysis.

2. 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.

3. Subjects who have a score on the Mini-Mental State Examination (MMSE) of 24 or below.

4. 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)

5. Subjects who have a history of deep venous thrombosis or pulmonary embolism, known hypercoagulability, or known family history of thromboembolic disease.

6. 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.

7. Subjects using chronic immunosuppressant therapy, including corticosteroids (> 5 mg/day of prednisone, or equivalent), or TNF-alpha antagonists.

8. Subjects on chronic immunosuppressive transplant therapy.

9. Subjects who have participated in another clinical study of new investigational therapies within 6 months prior to screening.

10. Subjects who have received any other stem cell therapy within 12 months prior to screening.

11. Subjects with known allergies or hypersensitivity to any component of the formulation and cellular therapies (i.e., penicillin or streptomycin).

12. Subjects who have a history of drug or alcohol abuse within the past 3 years.

13. Subjects who are known to be infected with Human Immunodeficiency Virus (HIV).

14. Subjects are currently hospitalized.

15. 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

16. Subjects who have any condition that in the opinion of the PI limits lifespan to < 1 year.

17. 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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