| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033307 |
| E.1.2 | Term | Overweight |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| • To assess the effect of HM11260C, in combination with a hypocaloric diet, on body weight over the 20 weeks from baseline in obese subjects |
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| E.2.2 | Secondary objectives of the trial |
• To assess the safety, tolerability, and immunogenicity of HM11260C, in combination with a hypocaloric diet, over the 20 weeks from baseline in obese subjects
• To assess the effect of HM11260C, in combination with a hypocaloric diet, on the metabolic profile, i.e., glucose parameters and lipid profile, of obese subjects over the 20 weeks from baseline.
o Glucose parameters: fasting plasma glucose (FPG), fasting insulin, HbA1c, c peptide
o Lipid profile: total cholesterol (TC), low density lipoprotein cholesterol (LDL C), high density lipoprotein cholesterol (HDL C), very low density lipoprotein cholesterol (VLDL C), and triglycerides (TG) |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Aged ≥ 18 and < 65 years at screening
2. BMI ≥ 30 kg/m2 or ≥ 27 kg/m2, with treated or untreated co morbidity(ies) (e.g., hypertriglyceridemia, dyslipidemia, hypertension, glucose intolerance, and sleep apnea), at screening.
3. Stable body weight (less than 5% change) for at least 3 months prior to screening
4. FPG < 126 mg/dL (7 mmol/L)
5. Considered to be in stable health, as determined by:
a) physical examination;
b) a medical history indicating either no clinically significant abnormalities or stable co morbid condition(s);
c) vital signs within normal ranges or if outside of the normal range are not deemed clinically significant in the opinion of the Investigator;
d) pre-study clinical laboratory findings within normal range, or if outside of the normal range, not deemed clinically significant in the opinion of the Investigator; and
e) a 12-lead electrocardiogram (ECG) showing no active ischemia
6. Not undergoing or in need of treatment for significant chronic disease, with the exception of stable (at least 3 months) treatment for hypertension, hypertriglyceridemia, and dyslipidemia, which is permitted
7. Female subjects of child-bearing potential must test negative for serum pregnancy at screening and by urine dipstick prior to dosing on the first day of dosing, and agree to use a highly effective method of birth control throughout the study and for at least 3 months after the last dose of study medication. Child-bearing potential is defined as women who have not been surgically sterilized for 6 weeks prior to screening or are post-menopausal ≤ 1 year. For women who are surgically sterilized or post-menopausal (> 1 year prior to the screening visit), the site will make an effort to retrieve medical records to document sterility. However, the absence of records will not exclude the subject. In the event that medical records cannot be obtained, serum and urine pregnancy testing will be conducted. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL at screening.
A highly effective method of birth control is considered to be 1 of the following:
a) An oral or implanted hormonal method of contraception (if it has been used for ≥ 3 months prior to study drug administration) while also using a barrier method (i.e., a condom or a diaphragm);
b) A hormone or copper intrauterine device if it has been in place for ≥ 3 months prior to study drug administration (subjects using a nonhormonal or copper intrauterine device should also use a barrier method [i.e., a condom or a diaphragm]);
c) A vasectomised partner;
d) Total abstinence is acceptable; however, the subject must use a highly effective method of contraception if the subject subsequently decides not to abstain.
8. Male subjects whose partners are female of child-bearing potential must be surgically sterilized (e.g., vasectomy) for at least 3 months prior to screening or agree to practice reliable birth control methods (condom and spermicide) during the conduct of the study and for at least 3 months after the last dose of study medication.
9. Ability and willingness to comply with all protocol procedures (e.g., correct handling of investigational product, compliance with visit schedule and dietary advice, and complete trial related questionnaires)
10. Written informed consent must be obtained before any study related assessment is performed. |
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| E.4 | Principal exclusion criteria |
1. Prior participation in any study of HM11260C.
2. Pregnant or nursing (lactating) women
3. BMI > 42 kg/m²
4. Drug induced obesity
5. Diabetes mellitus (type 1, 2, or other)
6. HbA1c > 6.5%
7. Previous surgical treatment for obesity (e.g., gastric bypass, ileal bypass, gastric banding) or anticipation of surgery during the study period that may interfere with completion or compliance with the protocol, or planned elective hospitalizations
8. Any known history of severe GI disease or intolerance, gastric emptying abnormality, or inflammatory bowel disease
9. Any previous GI bleeding or ulceration related to the use of non steroidal anti inflammatory drugs (NSAIDs) within 3 months before screening
10. Known history of acute or chronic pancreatitis with presence of raised serum amylase and lipase (> 3 times the upper limit of normal [ULN]) at screening
11. History of suicide attempts or recent history (within 2 years prior to screening) of major depression, anxiety, or other psychiatric disease requiring treatment with prescription medication including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), antipsychotics, and lithium.
12. Uncontrolled hypertension, defined as resting blood pressure (BP) > 150/90 mmHg at screening. If elevated, BP will be re-checked on a separate day within the screening period. If elevated on re check, subjects may be rescreened only after being on a stable antihypertensive therapy for 3 months. .
13. Has clinically significant abnormalities on 12 lead ECG, as determined by the Investigator
14. History of invasive cardiovascular surgical procedure within 6 months of screening; or severe heart or circulatory disease, within 6 months prior to screening
15. Personal or known family history of medullary thyroid carcinoma (MTC) or a genetic condition that predisposes to MTC
16. Abnormal thyroid stimulating hormone (TSH) laboratory value > 1.5 x ULN (ULN 5 mIU/L) value or abnormal TSH value lower than the normal value (< 0.5 mIU/L). Thyroid hormones are not permitted.
17. Fasting TG > 400 mg/dL.
18. LDL C > 160 mg/dL.
19. Liver disease, hepatitis, or clinically significant abnormal hepatic parameters suggestive of hepatic impairment (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase (AST) levels > 2.5 x ULN, or total bilirubin >1.5 x ULN unless the subject has a known history of Gilbert’s syndrome)
20. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or has > 60 mL/min/1.73 m2 and <90 mL/min/1.73 m2 with urine albumin to urine creatinine ratio > 30 mg/g. The eGFR will be based on the Cockcroft Gault formula at screening. Subject must not have a prior diagnosis of chronic kidney disease
21. Calcitonin levels > 20 pg/mL at screening
22. History of or positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) type 1 or 2 antibody
23. Use of cannabis (recreational or therapeutic) or a positive screen for drugs of abuse, barbiturates, or benzodiazepines that may potentially jeopardize a subject’s study compliance. Subjects who have been prescribed benzodiazepines, or low dose opiates for chronic conditions, may qualify for the study at the discretion of the investigator
24. A history of alcohol or drug abuse or drug addiction in the previous 12 months. Subjects should limit alcohol use to 14 units per week for women or 21 units per week for men (a unit is 1.5 ounces [44 mL] of 80 proof distilled spirits, 4 ounces [11.8 mL] of wine, or 1.2 ounces [355 mL] of 3 5% beer)
25. Heavy smoker (smokes more than 10 cigarettes/day or more than 2 cigars/day)
26. Has lost or donated more than 500 mL of blood within the last 2 months
27. Use of very-low calorie (1,000 kcal/day) liquid weight loss diet within 6 months
28. Known history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
29. Plans to or has had radioactive iodine test with intravenous administration of contrast material within 3 months of screening
30. Proliferative retinopathy or maculopathy treated within the 6 months before screening or requiring acute treatment
31. History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years before screening.
32. Severe neuropathy
33. Atypical sleep patterns (e.g., those working late night or graveyard shifts)
34. Any other condition or clinically significant abnormal findings during the physical examination, assessment of medical history (e.g. previous anaphylactic reactions or recent severe systemic illness, cognitive impairment), or clinical laboratory test results that, in the opinion of the Investigator, would make the subject unsuitable for the study or would put them at additional risk during participation
35. Has taken certain medications within the noted time period
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary variable is the body weight (to the nearest 0.1 kg [3.5 oz]), collected from subjects at baseline, Days 1, 8, 15, 22, 36, 50, 78, 106, and 141 during the treatment period.
The change in body weight from baseline to Week 21 (Day 141) and the number and the proportion of subjects who lose at least 5% of baseline body weight at Week 21 (Day 141) will be used to demonstrate the efficacy of each of the 4 doses of HM11260C versus placebo on fasting body weight reduction.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary variable is the body weight (to the nearest 0.1 kg [3.5 oz]), collected from subjects at baseline, Days 1, 8, 15, 22, 36, 50, 78, 106, and 141 during the treatment period.
The change in body weight from baseline to Week 21 (Day 141) and the number and the proportion of subjects who lose at least 5% of baseline body weight at Week 21 (Day 141) will be used to demonstrate the efficacy of each of the 4 doses of HM11260C versus placebo on fasting body weight reduction.
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| E.5.2 | Secondary end point(s) |
- Glucose Metabolism Parameters (FPG, fasting insulin, HbA1c, c peptide, and glucagon)
- Serum Lipid Profile |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Germany |
| Korea, Republic of |
| Netherlands |
| United States |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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