Safety Study of Intravenous MiraMSC in Older Adults With Mild to Moderate Frailty Syndrome

Official title

A Phase I, Open-Label Study to Evaluate the Safety and Tolerability of MiraMSC Administered Intravenously in Elderly Subjects With Mild to Moderate Frailty Syndrome

Overview

The purpose of this Phase I, open-label study is to evaluate the safety and tolerability of intravenous MiraMSC-FS-001 in older adults with mild to moderate frailty syndrome. MiraMSC-FS-001 is an investigational product consisting of allogeneic umbilical cord-derived mesenchymal stem cells (UCMSCs). Eligible participants will receive intravenous administration of MiraMSC-FS-001.

Detailed description

Frailty syndrome (FS) is an age-related clinical condition characterized by reduced physiological reserve and increased vulnerability to adverse health outcomes, including falls, hospitalization, disability, and mortality. Despite its growing prevalence in the aging population, effective treatment options for frailty syndrome remain limited.

MiraMSC-FS-001 is an investigational product consisting of allogeneic umbilical cord-derived mesenchymal stem cells (UCMSCs). Preclinical studies have demonstrated the immunomodulatory, anti-inflammatory, and regenerative properties of UCMSCs, supporting their clinical evaluation as a potential treatment for frailty syndrome. In addition, GLP toxicology studies demonstrated a favorable nonclinical safety profile for MiraMSC-FS-001, supporting its further clinical evaluation in humans.

This Phase I, open-label, dose-escalation study will evaluate the safety and tolerability of intravenous MiraMSC-FS-001 in older adults with mild to moderate frailty syndrome. Eligible participants will receive intravenous MiraMSC-FS-001 according to the study protocol and will undergo scheduled safety evaluations throughout the study. The results of this study are expected to provide clinical safety information to support the further development of MiraMSC-FS-001.

Interventions

• Drug MiraMSC-FS-001
  MiraMSC-FS-001 is an investigational biological product consisting of allogeneic umbilical cord-derived mesenchymal stem cells (UCMSCs). Two treatment cohorts are included: Cohort 1: 9 × 10⁷ cells per dose, administered by intravenous infusion every 2 weeks for a total of 3 doses (total dose: 2.7 × 10⁸ cells). Cohort 2: 9 × 10⁷ cells per dose, administered by intravenous infusion every 2 weeks for a total of 6 doses (total dose: 5.4 × 10⁸ cells).

Primary outcome measures

• Maximum Feasible Dose (MFD) of MiraMSC-FS-001 [Time frame: Within 14 days after the last study treatment administration (3-dose cohort: last dose on Day 28; 6-dose cohort: last dose on Day 70).]
• Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs) [Time frame: Baseline through Week 52]

Secondary outcome measures (7)

• Exercise performance measured by 6-minute walk test (6MWT) total distance [Time frame: Baseline, End of Treatment, Follow-up 1 (Week 24), Follow-up 2 (Week 36), and Follow-up 3 (Week 52)]
• Hand grip strength measured by maximum force using a hand dynamometer [Time frame: Baseline, End of Treatment, Follow-up 1 (Week 24), Follow-up 2 (Week 36), and Follow-up 3 (Week 52)]
• Physical performance measured by Short Physical Performance Battery (SPPB) total score [Time frame: Baseline, End of Treatment, Follow-up 1 (Week 24), Follow-up 2 (Week 36), and Follow-up 3 (Week 52)]
• Clinical Frailty Scale (CFS) score [Time frame: Baseline, End of Treatment, Follow-up 1 (Week 24), Follow-up 2 (Week 36), and Follow-up 3 (Week 52)]
• Quality of life measured by Falls Efficacy Scale-International (FES-I) questionnaire score [Time frame: Baseline, End of Treatment, Follow-up 1 (Week 24), Follow-up 2 (Week 36), and Follow-up 3 (Week 52)]
• Physical function measured by PROMIS Physical Function Short Form 20a score [Time frame: Baseline, End of Treatment, Follow-up 1 (Week 24), Follow-up 2 (Week 36), and Follow-up 3 (Week 52)]
• Quality of life measured by 36-Item Short Form (SF-36) survey score [Time frame: Baseline, End of Treatment, Follow-up 1 (Week 24), Follow-up 2 (Week 36), and Follow-up 3 (Week 52)]

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 Frailty Syndrome as assessed by the Investigator with a Clinical Frailty Scale score between 4 to

6\. 3. Subject will not start any new treatment for this condition during the study.

• The new treatment refers to any clinical study of new investigational therapies or any other stem cell therapies. Subject will be allowed to continue ongoing medications and therapies that are not prohibited treatment as listed in Section 6.4.1 and are deemed necessary by the Investigator for appropriate medical care. Minor modifications or dose adjustments to ongoing frailty- related treatments that were initiated prior to study enrollment and are not prohibited by the protocol may be implemented if deemed necessary by the Investigator for appropriate care; such adjustments will not be considered the initiation of a new treatment. \*\* 4. Subjects with body weight between 40 to 90 kg. 5. Subject is 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 unwill ing 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 disease 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 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 allergy 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 HIV.
• Subjects currently in hospital stay.
• 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 Principal investigator 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.
• Subjects with known or suspected bleeding disorders (including but not limited to hemophilia, von Willebrand disease, or platelet function disorders), or clinically significant coagulopathy (including abnormal PT, PTT, or INR) at screening.
• Subjects receiving medications that may increase the risk of bleeding or coagulopathy (such as anticoagulants, antiplatelet agents, or thrombolytics), unless medically necessary and approved by the Medical Monitor on a case- by-case basis.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07705464 · MiraMSC-FS-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗