Evaluate the Efficacy and Safety of EN001 in Patients With Sarcopenia

A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase 1/2 Clinical Trial to Evaluate the Efficacy and Safety of EN001 in Patients With Sarcopenia

A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase 1/2 Clinical Trial to Evaluate the Efficacy and Safety of EN001 in Patients with Sarcopenia

This clinical trial is a multicenter study consisting of two stages (Phase 1 and Phase 2). Phase 1 is designed with a 3+3 dose escalation design to evaluate the safety, including tolerability, of EN001 and explore efficacy. Phase 2 will evaluate the efficacy and safety of EN001 at the recommended Phase 2 dose (RP2D), as determined in Phase 1, compared with placebo.

--Phase 1 The study was designed using the traditional 3+3 dose escalation method to confirm the maximum tolerated dose (MTD) and determine the recommended phase 2 dose (RP2D).

Dose increase is carried out until the maximum tolerated dose (MTD) is confirmed at the high dose (Cohort 3), which is the maximum planned dose (MPD), or at a lower dose. The maximum tolerated dose (MTD) is defined as the highest dose at which the incidence of dose limiting toxicity (DLT) is lower than 33%. To determine the maximum tolerated dose (MTD), 3-6 test subjects from each dose cohort are enrolled and EN001 is administered three times at 4-week intervals, and dose-limiting toxicity (DLT) is evaluated until 4 weeks (visit 5).

Safety data for EN001 confirmed by the end of each Cohort (i.e., the end of the dose-limiting toxicity (DLT) evaluation of the last dosed subject in the Cohort) are comprehensively reviewed to determine all matters related to dose, such as increase or decrease in dose, and finally the recommended phase 2 dose (RP2D) is determined.

-- Phase 2 The Phase 2 is a randomized, double-blind, placebo-controlled clinical trial. Eligible subjects will be randomly assigned in a 1:1:1 ratio to Study Group 1 (EN001 Low dose, which is the recommended Phase 2 dose [RP2D]), Study Group 2 (EN001 High dose), or the placebo control group. The efficacy and safety of EN001 will be evaluated in comparison with placebo.

Inclusion Criteria:

• 1) Male or Female aged 60 years or older at the time of providing written consent. : Female subjects must meet one of the following criteria for postmenopausal women* :

  • Postmenopausal women:

    • Natural amenorrhea for 12 months
    • At least 6 weeks after surgical menopause (bilateral oophorectomy)

• 2) Individuals diagnosed with sarcopenia at the time of screening, based on the diagnostic criteria in Section 15.1 of the Asian Working Group for Sarcopenia(AWGS) 2019 guidlines, meeting (1) or (2) together with (3):

  • (1) Handgrip Strength: < 28kg(men), <18kg(women)
  • (2) 6-Metre Walk test<1.0m/s, or 5-Times Chair Stand Test ≥12seconds, or Short Physical Performance Battery(SPPB)≤9points
  • (3) Appendicular Skeletal Muscle Mass(ASM) by dual-energy X-ray absorptiometry(DXA):7.0kg/m^2(men), <5.4kg/m^2(women)

• 3) Individuals with a nutritional status score of ≥8points on the Screening component of the Long Mini Nutritional Assessment (Long MNA) at the time of screening

• 4) Individuals with a body weight of ≥35 kg and a Body Mass Index (BMI) of ≥15 kg/m² and <30 kg/m² at the time of screening

• 5) Individuals who have stably adhered to the diet and exercise regimen provided as part of this clinical trial during a run-in period of at least 4 weeks, and who are willing to comply with the regimen throughout the trial period

• 6) Individuals meeting the following laboratory test criteria at the time of screening and baseline:

  • Hemoglobin ≥10 g/dL,
  • White Blood Cell ≥2,500/μL,
  • Platelet ≥100,000/μL,
  • AST or ALT ≤3 × ULN,
  • International Normalized Ratio (INR) ≤1.3

• 7) Men who have agreed to use the appropriate contraceptive method(s), as specified in the protocol, from the date of signing the informed consent form through the end-of-study visit

  • Appropriate contraception is defined as follows and is achieved by applying one or more methods of contraception :

    • Partner's use of hormonal contraceptives

    • Partner's placement of an intrauterine device(IUD) or intrauterine system(IUS)

    • Sterilization procedure or surgery in the participant or partner

    • Double contraceptive method: use of a male condom in combination with other contraceptive methods [hormonal contraceptives, IUD/IUS placement, or sterilization procedure/surgery)

    • Abstinence: Absolute abstinence. If, in the examiner's judgment, the subject's age, occupation, lifestyle, or sexual orientation warrants contraception, strict abstinence from sexual intercourse is also acceptable. However, periodic abstinence (e.g. Karenda method, ovulation method, symptomatic temperature method), abstinence, and external vaginal ejaculation are not recognized as appropriate contraceptive methods.

      8) Individuals who(or whose legally authorized representative) have voluntarily agreed to participate in this clinical trial.

Exclusion Criteria:

• 1)Those with the following comorbidities confirmed at the time of screening and baseline

  • Patients with chronic kidney disease(CKD-EPI;Estimated Glomerular Filtration Rate(eGFR) <30 mL/min)

  • Individuals with uncontrolled thyroid disease(hyperthyroidism or hypothyroidism)

  • Patients with uncontrolled diabetes(HbA1c >8.5%)

  • Individuals with a neuromuscular or neurological disease (e.g., Parkinson's disease, amyotrophic lateral sclerosis [ALS], stroke affecting lower extremity function, muscular dystrophy, epilepsy, multiple sclerosis, etc.)

  • Individuals with severe cardiac disease classified as New York Heart Association (NYHA) Functional Classification III or IV (cardiomyopathy, unstable angina, myocardial infarction, valvular heart disease, arrhythmia, aortic disease, etc.)

  • Patients with uncontrolled hypertension((Systolic Blood Pressure (SBP) >180 mmHg or Diastolic Blood Pressure (DBP) >110 mmHg)

  • Any one of the serum virus tests (HBsAg, anti-HBc, anti-HCV, HIV Ag/Ab) is positive

    • (If anti-HBc positive) However, registration is possible if the HBV DNA test result is negative.
    • (If anti-HCV positive) However, registration is possible if the HCV RNA test result is negative.

  • Any malignancy within 5 years before screening (excluding basal cell carcinoma or squamous cell carcinoma of the skin, localized prostate cancer, or carcinoma in situ of the cervix may be enrolled even if the 5-year period has not elapsed, provided the investigator determines that the condition has been successfully treated and is in complete remission)

  • Any medical condition or history of surgery within 24 weeks prior to screening that may affect physical activity or function, including walking or exercise (e.g., fracture, severe knee or hip osteoarthritis, peripheral vascular disease)

• 2) Subjects with a confirmed history of the following treatments:

  • Systemic corticosteroids equivalent to prednisone >10 mg/day at screening

  • Any of the following medications that may affect muscle at screening:

    • Growth hormones (e.g., insulin-like growth factor-1 [IGF-1] analogues, somatropin)
    • Sex hormones (e.g., testosterone, estrogen, dehydroepiandrosterone [DHEA])
    • Ghrelin or megestrol acetate
    • Myostatin or myostatin inhibitors (e.g., stamulumab, domagrozumab, landogrozumab)
    • Bimagrumab
    • β-receptor blockers, ACE inhibitors, TNF-α antagonists, or GLP-1 agonists (Subjects receiving any of these medications at a stable dose for ≥12 weeks prior to screening and who plan to continue the treatment throughout the study may be enrolled.)
    • Troponin Activator

  • Prior treatment with any cell therapy or gene therapy at any time in their lifetime

  • Those who have received other investigational medicinal products or medical devices within 4 weeks prior to screening

• 3) Subjects with a Korean version of Montreal Cognitive Assessment (MoCA-K) score of less than 23 at screening

• 4) Persons with hypersensitivity to the components of clinical investigational products

• 5) Those who are unable to read or write

• 6) Those who are deemed inappropriate to participate in clinical trials according to the judgment of the investigator*

  • Examples of inappropriate reasons include, but are not limited to, the following:

    • History of drug or alcohol dependence or abuse
    • Medical history (e.g., autoimmune diseases such as myositis, dystonia, etc.) or surgical history that may affect efficacy evaluations, other than those specified in the inclusion/exclusion criteria
    • Subjects who are currently participating in, or plan to participate in, high-intensity bodybuilding, muscle-building, or muscle-strengthening programs (However, routine physical activity is not restricted.)