Subcutaneously Administered MD-18 for the Treatment of Obesity and Diabetes

NCT06739707 | Suspended Phase 1 DMC

• 1 other identifier: MD-18-02
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

A Multiple Dose, Randomized, Placebo-controlled, Dose-escalating Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered MD-18 for healthy subjects with overweight or obesity

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (12)

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of Adverse events.

  All adverse events, exacerbations of concomitant illnesses, or events known to be related to underlying disease processes or concomitant medications are to be recorded on the case report form throughout the study. Should there be more than 2 subjects receiving MD-18 with an adverse event grade 4 or 5 that is at least possibly related to MD-18, the study will be put on immediate hold and the data will be reviewed by the site Principal Investigator (PI) and the company Chief Medical Officer (CMO) before proceeding.

  Through study completion, an average of 8 months

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of body temperature.

  Body temperature measurements in Celsius (°C) will be conllected at the visits specified in the study protocol's Schedule of Events. If any clinically significant findings or machine/equipment errors occur, the measurement will be repeated. Any confirmed clinically significant result will be recorded as adverse events (AEs).

  During the following study visits: Screening, Day 1,7,14,21,28 and 35) and at the study visits of the 8 weeks study extension period on days 42,56,70,84 and 92 (Only for subjects that have agreed to participate from Cohort 7)

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of Serum chemistry.

  Collection of blood samples for serum chemistry

  During the screening visit, Day 1, 7,28,35 and at the study visits of Day 56,84 and 92 at the 8 weeks study extension period (Only for subjects that have agreed to participate from Cohort 7).

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of body weight

  Body weight (in kilograms) will be measured. To ensure consistency and accuracy, all subjects will be measured while wearing only undergarments or light clothing, without shoes. A calibrated scale will be used consistently throughout the study. In addition, weight measurements along with the screening height measurement will be combined to report BMI in kg/m\^2

  During each study visit and at the study visits of the 8 weeks study extension period (Only for subjects that have agreed to participate from Cohort 7)

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of Electrocardiogram examination.

  12-lead triplicate ECGs will be obtained. The ECG machine will automatically calculate the following: Heart rate ( refers to the number of contractions of the heart per minute) PR interval (PR interval is the time from the beginning of the P wave (atrial depolarization) to the beginning of the QRS complex. QRS complex (represents the depolarization of ventricles And the beginning of systole and ventricular contraction). QT interval (is the time from the beginning of the QRS complex, representing ventricular depolarization, to the end of the T wave, resulting from ventricular repolarization). QTc interval (is the QT interval corrected for heart rate).

  at screening (visit 1; Day -7) and days 7, 28 and 35. On Day 92 (for the 8 weeks extension period Only for subjects that have agreed to participate from Cohort 7).

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of respiration rate

  Respiration rate in breaths per minute will be collected at the visits specified in the study protocol's Schedule of Events. If any clinically significant findings or machine/equipment errors occur, the measurement will be repeated. Any confirmed clinically significant result will be recorded as adverse events.

  During the following study visits: Screening, Day 1,7,14,21,28 and 35) and at the study visits of the 8 weeks study extension period on days 42,56,70,84 and 92 (Only for subjects that have agreed to participate from Cohort 7)

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of heart rate

  Heart rate in beats per minute will be collected at the visits specified in the study protocol's Schedule of Events. If any clinically significant findings or machine/equipment errors occur, the measurement will be repeated. Any confirmed clinically significant result will be recorded as adverse events.

  During the following study visits: Screening, Day 1,7,14,21,28 and 35) and at the study visits of the 8 weeks study extension period on days 42,56,70,84 and 92 (Only for subjects that have agreed to participate from Cohort 7)

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of systolic and diastolic blood pressure

  Systolic and diastolic blood pressure in millimeters of mercury (mmHg) will be collected at the visits specified in the study protocol's Schedule of Events. If any clinically significant findings or machine/equipment errors occur, the measurement will be repeated. Any confirmed clinically significant result will be recorded as adverse events.

  During the following study visits: Screening, Day 1,7,14,21,28 and 35) and at the study visits of the 8 weeks study extension period on days 42,56,70,84 and 92 (Only for subjects that have agreed to participate from Cohort 7)

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of Hematology blood test

  Collection of Hematology blood test

  During the screening visit, Day 1, 7,28,35 and at the study visits of Day 56,84 and 92 at the 8 weeks study extension period (Only for subjects that have agreed to participate from Cohort 7).

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of coagulation panel

  Collection of blood samples for coagulation panel.

  During the screening visit, Day 1, 7,28,35 and at the study visits of Day 56,84 and 92 at the 8 weeks study extension period (Only for subjects that have agreed to participate from Cohort 7).

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of Urine analysis

  Collection of urine samples for Urine analysis

  During the screening visit, Day 1, 7,28,35 and at the study visits of Day 56,84 and 92 at the 8 weeks study extension period (Only for subjects that have agreed to participate from Cohort 7).

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of height

  Height (in centimeters) will be collected only at the screening visit and will be combined with the body weight measurements in order to calculate the body mass index (BMI) in kg/m2. A calibrated scale will be used consistently throughout the study.

  At the study screening visit (Day -28 to day -1 Pre-Treatment)

Secondary Outcomes (7)

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of pharmacokinetic for Area Under the Curve (AUC) analysis

  Before dose administration and at 0.5, 1, 2, 4, and 8 hours after dose administration on Days 1 and 28 of each dose level.

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of pharmacokinetic for Maximum concentration of MD-18 (Cmax) analysis

  Before dose administration and at 0.5, 1, 2, 4, and 8 hours after dose administration on Days 1 and 28 of each dose level.

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of pharmacokinetic for Minimum concentration of MD-18 between doses (Cmin) analysis

  Before dose administration and at 0.5, 1, 2, 4, and 8 hours after dose administration on Days 1 and 28 of each dose level.

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of Plasma samples for the pharmacokinetics analysis of Time to reach maximum concentration

  Before dose administration and at 0.5, 1, 2, 4, and 8 hours after dose administration on Days 1 and 28 of each dose level.

• To determine the safety and tolerability multiple subcutaneous doses of MD-18 in overweight or obese but otherwise healthy subjects, as assessed by the collection of pharmacokinetic for the analysis of Half-life (t½)

  Before dose administration and at 0.5, 1, 2, 4, and 8 hours after dose administration on Days 1 and 28 of each dose level.

Study Arms (7)

A dose of 74 mg of MD-18 or placebo three times per week for 4 consecutive weeks

EXPERIMENTAL

Cohort 1: Four subjects will be administered a dose of 74 mg of MD-18 and two will receive placebo subcutaneously three times per week for 4 consecutive weeks

Drug: MD-18; Drug: Placebo

A dose of 114 mg of MD-18 or placebo three times per week for 4 consecutive weeks

EXPERIMENTAL

Cohort 2: Four subjects will be administered a dose of 114 mg of MD-18 and two will receive placebo subcutaneously three times per week for 4 consecutive weeks.

Drug: MD-18; Drug: Placebo

A dose of 227 mg of MD-18 or placebo three times per week for 4 consecutive weeks

EXPERIMENTAL

Cohort 3: Four subjects will be administered a dose of 227 mg of MD-18 and two will receive placebo subcutaneously three times per week for 4 consecutive weeks.

Drug: MD-18; Drug: Placebo

A weekly dose of 302 mg of MD-18 or placebo for 4 consecutive weeks

EXPERIMENTAL

Cohort 4: Four subjects will be administered a weekly dose of 302 MD-18 and two will receive placebo subcutaneously for 4 consecutive weeks.

Drug: MD-18; Drug: Placebo

A dose of 302 mg of MD-18 or placebo three times per week for 4 consecutive weeks

EXPERIMENTAL

Cohort 5: Four subjects will be administered a dose of 302 mg of MD-18 and two will receive placebo subcutaneously three times per week for 4 consecutive weeks.

Drug: MD-18; Drug: Placebo

A daily dose of 302 mg of MD-18 or placebo for 4 consecutive weeks

EXPERIMENTAL

Cohort 6: Four subjects will be administered a daily dose of 302 mg of MD-18 and two will receive placebo subcutaneously for 4 consecutive weeks.

Drug: MD-18; Drug: Placebo

The highest tolerated dose/dose-frequency identified in the first six cohorts

EXPERIMENTAL

Cohort 7: Twelve non-diabetic obese subjects will be treated with the highest tolerated dose/dose-frequency identified in the first six cohorts and six subjects will be administered placebo.

Drug: MD-18; Drug: Placebo

Interventions

MD-18 DRUG

MD-18 administered subcutaneously to healthy individuals with overweight or obesity.

A daily dose of 302 mg of MD-18 or placebo for 4 consecutive weeks; A dose of 114 mg of MD-18 or placebo three times per week for 4 consecutive weeks; A dose of 227 mg of MD-18 or placebo three times per week for 4 consecutive weeks; A dose of 302 mg of MD-18 or placebo three times per week for 4 consecutive weeks; A dose of 74 mg of MD-18 or placebo three times per week for 4 consecutive weeks; A weekly dose of 302 mg of MD-18 or placebo for 4 consecutive weeks; The highest tolerated dose/dose-frequency identified in the first six cohorts

Placebo DRUG

Placebo administered subcutaneously to healthy individuals with overweight or obesity.

A daily dose of 302 mg of MD-18 or placebo for 4 consecutive weeks; A dose of 114 mg of MD-18 or placebo three times per week for 4 consecutive weeks; A dose of 227 mg of MD-18 or placebo three times per week for 4 consecutive weeks; A dose of 302 mg of MD-18 or placebo three times per week for 4 consecutive weeks; A dose of 74 mg of MD-18 or placebo three times per week for 4 consecutive weeks; A weekly dose of 302 mg of MD-18 or placebo for 4 consecutive weeks; The highest tolerated dose/dose-frequency identified in the first six cohorts

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged 18-70 years, both genders.
• BMI:
• Cohorts 1-6: 25-34.9
• Cohort 7: 30.0-44.9
• HbA1c \<6.5%
• Healthy as determined by a physician, based on history, medical examination, vital signs, laboratory tests, cardiac monitoring and respiratory function. History must comply with the following:
• Absence of clinically significant illness or major surgery within the preceding 12 weeks.
• Absence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and/or metabolic disease as per PI decision.
• Male subjects with female partners of childbearing potential must agree to utilize an approved contraceptive during the study.
• Female subjects of child-bearing potential with negative urine pregnancy test at screening and who agree to use contraception during the study.
• Female subjects of non-child-bearing potential (i.e. tubal ligation, hysterectomy, or postmenopausal).
• Subjects must provide written informed consent and be willing and able to comply with study procedures.

You may not qualify if:

• History of excessive alcohol use (defined as \>21 drinks per week for males and \>14 drinks per week for females), recreational drug use within the past three months, or failure on urinary drug screen. Note: use of Cannabinoids for medical purposes is allowed.
• Pregnant or breastfeeding within six months of screening assessment.
• Substantial changes in eating habits or exercise routine within the preceding three months.
• Evidence of eating disorders.
• \>5% weight change in the past three months.
• Bariatric surgery within the past five years.
• Moderate renal impairment ( Glomerular filtration rate\<60 mg/mL/1.73m2)
• Liver function tests greater than twice the upper limit of normal upon repeated measurements.
• Diseases interfering with metabolism and or ingestive behavior (e.g., myxedema, Cushing's disease, schizophrenia, major psychoses, unmanaged depression).
• Use of medications affecting body weight within the past three months, unless on a stable dose, with weight stability in the preceding three months. These medications include:
• Drugs approved for the treatment of obesity
• Cyproheptadine or medroxyprogesterone
• Atypical anti-psychotic drugs
• Tricyclic antidepressants
• Lithium, MAO's, glucocorticoids

Sponsors & Collaborators

• Cohen Global, Ltd.: lead

Study Sites (1)

Sheba Medical Center

Ramat Gan, Please Select, 522651, Israel

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study medication will be supplied in labelled vials,clearly identifying the contents and indicating that the product is an investigational drug. An unblinding pharmacist at the clinical site will be responsible for the appropriate amount of vials to be dispnsed to each subject according to the randomization scheme. A blinded nurse will draw the correct amount of study medication into a syringe based on the subject's assigned arm, and administer the injection to the subject.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dosing will be in 7 dose cohorts. Cohorts 1 through 6 will be comprised of six subjects in each cohort using 4:2 (active: placebo) randomization. Thus, there will be four subjects receiving drug and two receiving placebo in each cohort. Cohort 7 will comprise 18 Obese subjects, in which 12 subjects will receive MD-18 and six will receive placebo. A total of 54 subjects will be enrolled in this study, with 36 receiving MD-18 and 18 receiving placebo. There is no need to wait for the completion of one cohort (Day 28) before proceeding to the next. Once all subjects for Cohort 1 have been recruited, the site should begin recruitment for Cohort 2, even while Cohort 1 is still ongoing. This process should continue for subsequent cohorts. The highest dose that is safe and tolerable in all subjects will be determined as the Maximum Tolerable Dose .

Study Record Dates

• First Submitted: December 4, 2024
• First Posted: December 18, 2024
• Study Start: January 2, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 20, 2026

Record last verified: 2026-05

Locations

IL (1)