Assessment of the Safety, Tolerability, and Pharmacokinetic of HM201

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Crohn's Disease; Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Drug: HM201

Detailed Description

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 9 subjects; 2 will receive the placebo while 7 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.

• Study Type: Interventional
• Enrollment (Anticipated): 68
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Cameron Johnson; Phone Number: +61 3 9076 8906; Email: c.johnson@nucleusnetwork.com.au

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Recruiting
      • Nucleus Network Pty Ltd
      • Contact: Cameron Johnson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Healthy male or non-childbearing potential female
2. BMI ≥18.0 and ≤32.0 kg/m2
3. Good health based on past medical history, medication use, vital signs and physical exam.
4. Normal renal and hepatic function.
5. Female partners of child bearing potential must agree to use contraception.

Key Exclusion Criteria:

1. Clinically significant medical history.
2. Significant drug allergy.
3. Use of experimental drug within 3 months prior.
4. Previously received HM201, AM and other derivatives.
5. History of old myocardial infarction.
6. Diagnosed with malignant tumor or history of treatment for malignant tumor.
7. History of drug or alcohol abuse.
8. Use of omitted medicines or substance opposing objective of study.
9. COVID19 vaccine administered within 14 days of initiation of investigational product or if to receive additional dose within 30 days of investigational product administration.
10. Use of tobacco/nicotine in excess of ≥ 5 cigarettes a day and unable or unwilling to prohibit smoking during admission to site.
11. 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.
12. 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.
13. 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.
14. Clinically relevant findings in ECG.
15. Systolic blood pressure below 100 mmHg or above 140 mmHg at screening.
16. Diastolic blood pressure above 90 mmHg at screening.
17. Heart rate below 40 beats/min or above 100 beats/min at screening.
18. Symptom of orthostatic hypotension is found at screening or before investigational product administration (Day -1).
19. 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.
20. Positive to syphilis.
21. Positive to urine drug test.
22. Positive alcohol breath test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAD Cohorts 1 to 4: Participants receiving HM201; 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; HM201 will be administered intravenously.; Other Names: Pegylated human adrenomedullin
Placebo Comparator: SAD Cohorts 1 to 4: Participants Receiving Placebo; Each SAD cohort participant will be randomized to receive placebo.	Drug: Placebo; Placebo will be administered intravenously.; Other Names: Matching Placebo
Experimental: MAD Cohorts 1 to 4: Participants Receiving HM201; 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; HM201 will be administered intravenously.; Other Names: Pegylated human adrenomedullin
Placebo Comparator: MAD Cohorts 1 to 4: Participants Receiving Placebo; Each MAD cohort participant will be randomized to receive placebo once a week for 4 weeks.	Drug: Placebo; Placebo will be administered intravenously.; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Syneos Health
• Collaborators: Himuka AM Pharma Corp.
• Investigators: Principal Investigator: Kristi McLendon, MD, Nucleus Network Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Cardiotonic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenomedullin
• Other Study ID Numbers: HM201-AUS-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No