Safety and Efficacy of IMM01-STEM Against Placebo on Muscle Performance in Seniors With Obesity and Muscle Weakness

Prior treatment

• Study participant is taking or has taken a prohibited medication as defined in Section 6.8.2 of the clinical protocol.
• Weight loss (bariatric) surgery of any type including biliopancreatic diversion with duodenal switch, gastric bypass, sleeve gastrectomy, adjustable gastric banding, 1 year prior enrollment.
• Study participant has previously participated in this study or participant has previously been assigned to treatment in a study of the medication under investigation in this study.
• Study participant has been exposed to an investigational drug or device within 1 year, prior to the first dose of IMP, or is currently participating or planning to participate in another study of an investigational drug.
• Current physical/rehabilitation therapy (except for passive physical therapy)
• Substance abuse (including but not limited to alcohol, cannabis, narcotics, pain medication) as judged by the investigator.

Other illness

• Unmanaged/uncontrolled comorbidities (examples include high blood pressure, hyperglycemia, unstable angina, deep vein thrombosis, hepatic cirrhosis, peptic ulcers, complicated GERD, COPD, asthma etc.) as judged by the investigator.
• Current diagnosis of major psychiatric disorders that may impact participation, as judged by the investigator.
• Conditions that interfere with gait balance or mobility, such as severe arthritis of lumbo-sacral area, hip or lower extremities if gait speed is used for inclusion criteria
• Conditions that interfere with ability to measure grip strength including hand arthritis, carpal tunnel syndrome and elbow tendinitis if hand grip criteria is used for inclusion
• Study participant has current or past history of invasive malignancy (5 years) excluding non-melanoma skin cancer.
• Inflammatory conditions requiring regular use of oral or parenteral corticosteroids (Raynaud phenomenon, scleroderma, rheumatoid arthritis, LED etc.).
• Cushing's syndrome, Graves disease (hyperthyroidism), or other condition of hormone imbalance caused by genetic or auto-immune disorder. Exceptions include controlled hypothyroidism and polycystic ovarian syndrome.
• Severe cardiovascular disease (including New York Heart Association \[NYHA\] class III or IV congestive heart failure, clinically significant valvular disease, history of cardiac arrest, presence of an implantable defibrillator)
• Parkinson's disease, multiple sclerosis or other progressive neurological disorders
• Participant has had a change in medication to manage comorbid condition(s) (including diabetes, hypertension, asthma, and cardiovascular disease) within 1 month of the Screening visit.
• Study participant is known positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb) or human immunodeficiency virus-1/2 antibody (human immunovirus 1/2Ab)

Lab values

• Type 1 Diabetes Mellitus, insulin-dependent Type 2 Diabetes mellitus, or hemoglobin A1C level \>7.0%
• Renal disease requiring dialysis, or known renal insufficiency (moderate or severe reduction in GFR≤30 ml/min/1.73 m2)
• Occasional alcohol consumption is acceptable, however the participants will be prohibited to consume alcohol 72 hours (3 days) prior medical and laboratory visits

Other

• Severe obesity, or class III obesity (CDC criteria, BMI \>40)
• Chest pain, severe shortness of breath, or occurrence of other safety concerns during the baseline functional tests
• Woman of Childbearing Potential (WOCBP) (defined as women with less than 12 months of amenorrhea).
• Unable to understand and/or perform the functional tests, as judged by the Investigator.
• Smoking or vaping of products containing nicotine, tobacco or any other products, currently and in the past 1 year.
• All participants will be encouraged to follow a healthy diet. Caloric restriction will not be pursued.
• Smoking of tobacco, marijuana or any other inhaled products (vaping) are prohibited during treatment and during the follow-up period
• There is no restriction on caffeine consumption
• All participants in the trial (including placebo group) will be encouraged to increase daily physical activities. The participants can follow any preferred physical activity (walking, running, swimming, bicycle, treadmill, etc.), it can be evaluated by summed duration of a variety of activities, such as household work. The activity is measured by the sensors of the wearable activity tracker; thus, the nature of the activity is not critical.
• Activities that are conductive to falls and accidents are discouraged. Examples include horse riding, skiing, skydiving, scuba diving, mountain biking, bungee jumping, etc.
• Participant must be able to wear an activity tracker device daily, optional during sleep, and must be aware of the requirements to charge the tracker or transfer the data.

• Sex: male or female
• Age 60 to 80 years of age at the time of signing the informed consent.
• Race/nationality: all races and ethnicities accepted for which there are validated reference values for obesity and sarcopenia diagnostic criteria
• Disease characteristics: To be eligible, the participant must meet at least one criterion for obesity and at least one criterion for sarcopenia, as defined below:
  • Obesity:
  • Abdominal obesity defined by a waist circumference ≥ 40 inches (102 cm) for men, ≥ 35 inches (88 cm) for women (American Heart Association) Abdominal obesity as a waist-to-hip ratio of at least 0.90 in men and 0.85 or more for women (World Health Organization)
  • Sarcopenia:
  • Grip strength women: \< 16 kg, men: \< 27 kg in the dominant hand Gait speed \< 0.8 m/s (men and women)
  • Acceptable stages:
  • STAGE I: No complications attributable to altered body composition and skeletal muscle functional parameters STAGE II: Presence of up to two complications attributable to altered body composition and skeletal muscle functional parameters (e.g. metabolic syndrome components, disabilities resulting from high fat mass and/or low muscle mass, cardiovascular and respiratory disease). Limitations apply (see exclusion criteria).
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the STEM-META clinical protocol
• In order to understand the nature of this study it is expected that most participants will be able to speak, read, and understand English, or Spanish however, additional translations of the informed consent may be made available after study initiation to include additional languages for participants
• Study participant is willing and able to comply with all study requirements, according to the judgment of the Investigator.
• To be eligible for enrollment and for each treatment administration, the vital signs pre-dose, should be in the following ranges. If the vitals are outside of the range, will be reassessed 3 times at 10 minutes resting intervals.
  • Heart rate \>50 and \<100 bpm Systolic pressure \>100 and \<170 mmHg Diastolic pressure \>50 and \<100 mmHg Blood oxygenation (by pulse-oximetry) \>95%