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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
132
\- Phase1-Cohort 1: EN001 Low dose administered intravenously (IV) 3 times at 4 week intervals.
-Phase2-Cohort 2 : EN001 Medium dose administered intravenously (IV) 3times at 4 week intervals.
-Phase1-Cohort 3 : EN001 High dose administered intravenously (IV) 3times at 4 week intervals.
Samsung Medical Center
Seoul, South Korea
[Phase1] Dose limiting toxicity (DLT) and adverse drug reactions related to discontinuation of investigational product administration
Present the frequency and percentage of dose-limiting toxicity (DLT) occurrence across dose cohorts, along with detailed information on the types of DLTs. Adverse events related to discontinuation of clinical investigational drug administration, discontinuation of clinical investigational drug administration Regarding related adverse drug reactions, the number of subjects in each cohort, incidence rate (%), and Two-sided 95% confidence intervals and number of occurrences are presented.
Time frame: Up to 12 weeks
[Phase2] Change from baseline in the SPPB(Short Physical Performance Battery) at Week 24
For all efficacy outcome measures, descriptive statistics (number of subjects, mean, standard deviation, median, minimum, and maximum) will be presented by treatment group and assessment time point, along with two-sided 95% confidence intervals.
Time frame: at Week 24
[Phase1, Phase2] SPPB(Short Physical Performance Battery) score change
Present the subject count, mean, standard deviation, median, minimum, and maximum for the changes at each time point within each dosage group.
Time frame: At 4,8,12, 18, and 24 weeks compared to baseline(Visit2)
[Phase1, Phase2] Change in handgrip strength
Present the subject count, mean, standard deviation, median, minimum, and maximum for the changes at each time point within each dosage group.
Time frame: At 4,8,12, 18, and 24 weeks compared to baseline(Visit2)
[Phase1, Phase2] Change in time to complete the 5-Times Chair Stand Test
Present the subject count, mean, standard deviation, median, minimum, and maximum for the changes at each time point within each dosage group.
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-Phase2-Cohort 1 : EN001 Low dose(Recommended Phase 2 Dose\[RP2D\] of EN001) administered intravenously (IV) 3times at 4 week intervals.
-Phase2-Cohort2 : EN001 High dose(Recommended Phase 2 Dose\[RP2D\] of EN001) administered intravenously (IV) 3times at 4 week intervals.
-Phase2-Placebo : EN001 Placebo administered intravenously (IV) 3times at 4 week intervals.
Time frame: At 4,8,12, 18, and 24 weeks compared to baseline(Visit2)
[Phase1, Phase2] Change in 6-Minute Walk Test (6MWT) distance
Present the subject count, mean, standard deviation, median, minimum, and maximum for the changes at each time point within each dosage group.
Time frame: At 4,8,12, 18, and 24 weeks compared to baseline(Visit2)
[Phase1, Phase2] Change in Appendicular Skeletal Muscle Mass (ASM) measured by DXA
Present the subject count, mean, standard deviation, median, minimum, and maximum for the changes at each time point within each dosage group.
Time frame: At 12 and 24 weeks compared to baseline(Visit2)
[Phase1, Phase2] SarQoL domain and total score change
Present the subject count, mean, standard deviation, median, minimum, and maximum for the changes at each time point within each dosage group.
Time frame: At 12 and 24 weeks compared to baseline(Visit2)
[Phase1, Phase2] Change in Skeletal Muscle Mass Index(SMI)
Present the subject count, mean, standard deviation, median, minimum, and maximum for the changes at each time point within each dosage group.
Time frame: At 24 weeks compared to baseline(Visit2)
[Phase1, Phase 2] Adverse Event
By group that Number of subjects, incidence rate (%), confidence interval (two-sided 95%), presents the number of occurrences. Additional, The pre-treatment adverse event that occurred before administration of clinical trial drugs is presented in detail.
Time frame: Up to 24weeks. However, adverse drug reactions that persist at the end of the clinical trial will be followed up until the possible adverse reactions are resolved or it is determined that further follow-up is not meaningful.
[Phase1, Phase2] Vital sign
Number of participants with clinically significant abnomalities in vital signs after EN001 administration. Vital Signs include blood pressure (mmHg), pulse (times/minute), respiratory rate (times/minute), and body temperature (℃) and will be assessed. By cohort and visit, present continuous variables with subject count, mean, standard deviation, median, minimum, and maximum. For categorical variables, provide shift table.
Time frame: Up to 24 weeks
[Phase1, Phase2] Laboratory examination
Number of participants with clinically significant abnormalities in Laboratory parameters after EN001 administration. Hematological tests, Blood chemical tests, Blood coagulation test, Urine test, Serum virus test. It is conducted through blood and urine collection, and the PI checks whether the test results are normal, abnormal, and clinically significant.
Time frame: Up to 24 week. Serum virus testing is performed only during screening. At Baseline, Week4 and Week8, hematological tests, blood chemical tests, D-dimer are performed before and within 4 hours after administration of the IP.
[Phase1, Phase2] electrocardiography
Number of participants with clinically significant abnormalities in electrocardiography after EN001 administration. Based on the PR Interval, QRS Duration, QTc Interval and QTcF Interval, PI checks whether the test results are normal, abnormal, and clinically significant. by cohort and visit, present continuous variables with subject count, mean, standard deviation, median, minimum, and maximum. For categorical variables, provide shift table.
Time frame: At Baseline, Week 4, Week 8, Week 12, Week 24
[Phase1, Phase2] X-ray
by cohort and visit, present continuous variables with subject count, mean, standard deviation, median, minimum, and maximum. For categorical variables, provide shift table.
Time frame: Before administration of investigational product at Baseline, within 4 hours after completion of administration, and at Weeks 4, 8, 12, and 24
[Phase1, Phase2] Physical Examinations
Number of participants with clinically significant abnormalities in Physical Examinations after EN001 administration. Based on general appearance, head,ears/eyes/nose/throat, cardiovascular, respiratory, abdomen, skin, lymph nodes, extremities, musculoskeletal and neurologic, PI checks whether the test results are normal, abnormal, and clinically significant. By cohort and visit, present continuous variables with subject count, mean, standard deviation, median, minimum, and maximum. For categorical variables, provide shift table.
Time frame: Up to 24 weeks