Assessment of the Safety, Tolerability, and Pharmacokinetic of HM201

Study Overview
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Brief Summary
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This will be a single centre, Phase 1, Placebo-controlled, Randomized, Doubleblind, SAD & MAD Study to Assess the Safety, Tolerability and PK of HM201 in Healthy Subjects.

Detailed Description
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Objective of the study is to assess the safety, tolerability, and PK of single and multiple intravenous administration of HM201. The study design consists of a SAD study of 4 cohorts, 8 subjects each cohort and a different dose level per cohort. In each cohort 2 will receive the placebo while rest of group will be administered with HM201. A total of 32 subjects are planned for the SAD study. MAD part will begin after cohort 1 and 2 of SAD is completed. MAD will consist of 8 subjects; 2 will receive the placebo while 6 will be administered with HM201. MAD will be conducted in a dose escalation manner with 4 weekly doses administered to all subjects. One randomization scheme will be produced for each cohort separately.

Official Title
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A First-in-human, Double-blind, Placebo-controlled, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Intravenous Doses of HM201 (Pegylated Human Adrenomedullin) in Healthy Subjects (Adults)

Conditions
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Ulcerative Colitis, Crohn's Disease

Intervention / Treatment
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* Drug: HM201
* Drug: Placebo
* Drug: HM201
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy male or non-childbearing potential female BMI ≥18.0 and ≤32.0 kg/m2 Good health based on past medical history, medication use, vital signs and physical exam. Normal renal and hepatic function. Female partners of child bearing potential must agree to use contraception. Key Exclusion Criteria: Clinically significant medical history. Significant drug allergy. Use of experimental drug within 3 months prior. Previously received HM201, AM and other derivatives. History of old myocardial infarction. Diagnosed with malignant tumor or history of treatment for malignant tumor. History of drug or alcohol abuse. Use of omitted medicines or substance opposing objective of study. COVID19 vaccine administered within 14 days of initiation of investigational product or if to receive additional dose within 30 days of investigational product administration. Use of tobacco/nicotine in excess of ≥ 5 cigarettes a day and unable or unwilling to prohibit smoking during admission to site. Daily consumption of more than 1L of caffeine/xanthine beverage which cannot be discontinued more than 24 hours prior to dosing of investigational product and/or ECG measurement. Regular use of nutraceuticals (e.g., St. John's wort, ginseng, ginkgo biloba, Chinese herbs, and melatonin) within 1 week before administration of investigational product. Donation of plasma or platelet or 200 mL of whole blood within 4 weeks or 400 mL whole blood within 3 months before administration of investigational product. Clinically relevant findings in ECG. Systolic blood pressure below 100 mmHg or above 140 mmHg at screening. Diastolic blood pressure above 90 mmHg at screening. Heart rate below 40 beats/min or above 100 beats/min at screening. Symptom of orthostatic hypotension is found at screening or before investigational product administration (Day -1). Hepatitis B virus surface antigen (HBsAg), hepatitis B virus core antibody (HBcAb) hepatitis C virus antibodies (anti-HCV) or human immunodeficiency virus (HIV) antigen and antibody at screening. Positive to syphilis. Positive to urine drug test. Positive alcohol breath test.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: SAD & MAD study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD Cohorts 1 to 4: Participants receiving HM201<br>Each SAD cohort participant will be randomized to receive 1 of 4 escalating doses (0.01 mg/kg (2 nmol/kg); 0.03 mg/kg (5 nmol/kg); 0.06 mg/kg (10 nmol/kg); 0.12 mg/kg (20 nmol/kg). | Drug: HM201<br>* HM201 will be administered intravenously.<br>* Other names: Pegylated human adrenomedullin;|
| Placebo Comparator: SAD Cohorts 1 to 4: Participants Receiving Placebo<br>Each SAD cohort participant will be randomized to receive placebo. | Drug: Placebo<br>* Placebo will be administered intravenously.<br>* Other names: Matching Placebo;|
| Experimental: MAD Cohorts 1 to 4: Participants Receiving HM201<br>Each MAD cohort participant will be randomized to receive a once a week dose of 1 of 4 escalating doses (0.01 mg/kg (2 nmol/kg); 0.03 mg/kg (5 nmol/kg); 0.06 mg/kg (10 nmol/kg), 0.12 mg/kg (20 nmol/kg) for 4 weeks. | Drug: HM201<br>* HM201 will be administered intravenously.<br>* Other names: Pegylated human adrenomedullin;|
| Placebo Comparator: MAD Cohorts 1 to 4: Participants Receiving Placebo<br>Each MAD cohort participant will be randomized to receive placebo once a week for 4 weeks. | Drug: Placebo<br>* Placebo will be administered intravenously.<br>* Other names: Matching Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of treatment-emergent adverse event, serious adverse event and discontinuation. |  | Up to 15 days post last infusion for both SAD & MAD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of HM201 |  | SAD: Up to Day 15. MAD: Up to Day 36 | 
| Pharmacokinetic assessment 1 | Area under the plasma concentration versus time curve (AUC) | SAD: Up to Day 15. MAD: Up to Day 36 | 
| Pharmacokinetic assessment 2 | Peak Plasma Concentration (Cmax) | SAD: Up to Day 15. MAD: Up to Day 36 | 
| Pharmacokinetic assessment 3 | Time of peak plasma concentration (Tmax) | SAD: Up to Day 15. MAD: Up to Day 36 | 
| Pharmacokinetic assessment 4 | Concentration at the last planned timepoint prior to dosing (Ctrough) | MAD: Up to Day 36 | 
| Pharmacokinetic assessment 5 | Mean residence time (MRT) | SAD: Up to Day 15. MAD: Up to Day 36 | 
| Pharmacokinetic assessment 6 | Drug clearance (CL) & Clearance at steady state (CLss) | SAD: Up to Day 15. MAD: Up to Day 36 | 
| Pharmacokinetic assessment 7 | Volume of distribution at steady state (Vss) & during terminal phase (VZ) | SAD: Up to Day 15. MAD: Up to Day 36 | 
| Pharmacokinetic assessment 8 | Half life (T1/2) | SAD: Up to Day 15. MAD: Up to Day 36 |