A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial Investigating the Safety and Efficacy of Longeveron Allogeneic Human Mesenchymal Stem Cells (LMSC) Administration in Patients With Aging Frailty.

JRCT ID: jRCT2043200038

Registered date:04/08/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Aging Frailty
• Date of first enrollment: 15/11/2022
• Target sample size: 45
• Study type: Interventional

Intervention(s)

LMSC 5.0*10^7: single peripheral i.v.
LMSC 1.0*10^8: single peripheral i.v.
Placebo: single peripheral i.v.

Outcome(s)

• Primary Outcome: Incidence of any serious adverse event (SAE), occurring within the first 30 days after infusion.

Key inclusion & exclusion criteria

• Age minimum: >= 70age old
• Age maximum: <= 89age old
• Gender: Both

Include criteria

1.They are willing and able to provide written informed consent and comply with all the procedures described in this protocol.
2. Age 70-89 years at the time of signing the informed consent form.
3. A flail based on the definitions of the Japanese version of CHS criteria, which is a flail phenotype model, i.e., it meets at least 3 of the following criteria:
a.Weight loss: Unintentional weight loss of at least 2 kg in the previous 6 months.
b.Muscle weakness: Grip strength<28 kg (male) or<18 kg (female)
c.Fatigue: I felt like I was tired in the last two weeks.
d.Walking speed decrease: Walking speed is less than 1.0 m/s
e.Low Physical Activity: Subject answered "not even once a week" to any of the following questions:
i.Are you performing moderate-intensity exercise or sports for health purposes?
ii.Do you exercise or exercise lightly for health purposes?

Exclude criteria

1.Patients who are unwilling or unable to perform any of the assessments described in this protocol.
2.Patients with a diagnosis of neurological disease such as (but not limited to) cerebrovascular disease with sequelae such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, muscle weakness, and gait disturbance, or patients with a diagnosis of dementia.
3.Patients with Mini-Mental State Examination (MMSE) scores of 23 or less.
4.Patients with poorly controlled blood glucose levels (>= 8.0% HbA1c).
5.2.5 Patients with a history of malignancy within a year (patients with a previous malignancy must be cancer free for 2.5 years). Except for basal cell carcinoma, melanoma in situ and cervical cancer treated therapeutically.
6.Patients considered by the investigator to have a life expectancy of 1 year or less.
7.Patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.).
8.Patients on immunosuppressive therapy, such as corticosteroids (prednisolone can be given < 5 mg/day, other exceptions include hormone replacement therapy, steroidal asthma medication, topical corticosteroids)
9.Patients on TNF-alpha blockers.
10.Hep B Patients with a positive hepatitis virus test.
11.Hep C Patients with a positive hepatitis virus test, HIV1/2 test, or syphilitic test.
12.Patients with blood oxygen saturation < 93% (measured by pulse oximetry) at rest.
13.Patients with or suspected of having alcohol or substance abuse within 3 years prior to screening.
14.Patients with a history of hypersensitivity to bovine or porcine-derived ingredients.
15.Patients with hypersensitivity to dimethyl sulfoxide (DMSO).
16.Organ transplant recipients (excluding corneal, bone, skin, ligaments, or tendon grafts).
17.Patients enrolled (or planned to enroll) as transplant-seekers of any organ (excluding the cornea).
18.Patients with clinically significant abnormalities in screening parameters, including, but not limited to, the following.
a.Haemoglobin < 10.0 g/dL
b.WBC < 2,500 or platelet < 100,000
c.Liver dysfunction with enzymes (AST and ALT) greater than 3 times the upper limit of normal.
d.Blood clotting abnormalities (INR >= 1.3) not due to ameliorable causes (e.g., warfarin and/or factor Xa inhibitors.
19.Patients with uncontrolled hypertension (resting systolic blood pressure > 180 mm Hg at screen or diastolic blood pressure > 110 mm).
20.Patients with unstable angina pectoris or uncontrolled or severe peripheral artery disease within the past 3 months.
21.Patients with New York Heart Association (NYHA) class III or IV or congestive heart failure with ejection fraction <=25%.
22.Patients who underwent coronary artery bypass surgery, angioplasty, revascularization for peripheral vascular disease, or developed myocardial infarction within the previous 3 months.
23.Patients with severe pulmonary dysfunction [patients with acute exacerbation of stage III or IV (GOLD class) chronic obstructive pulmonary disease and/or PaO2 levels < 60 mmHg].
24.Patients with partial ileal bypass or other significant intestinal malabsorption.
25.Patients with progressive liver or kidney disease.
26.Patients with cognitive or language impairment who are unable to provide consent or assess study items.
27.Patients who are currently hospitalized or who reside in nursing homes or long-term care facilities.
28.Patients who are currently participating in other clinical trials,clinical studies,etc., or were participating within 30 days before consent.(However,observational studies without intervention are acceptable.)
29.There have been or are present any symptoms, treatments, laboratory abnormalities, or other conditions that may affect the evaluation of the study or interfere with patient participation during the study.

Related Information

• Primary Sponsor: Matsui Yasumoto
• Secondary Sponsor: Arai Hidenori
• Source(s) of Monetary Support: Longeveron Inc.