Assessment of the Safety, Tolerability, and Pharmacokinetic of HM201

Ulcerative Colitis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05088369
• Other study ID #: HM201-AUS-001
• Status: Completed
• Phase: Phase 1
• Start date: November 11, 2021
• Est. completion date: December 19, 2022

Study information

• Verified date: January 2023
• Source: Syneos Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 19, 2022
• Est. primary completion date: December 19, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• Ulcerative Colitis

Intervention

Drug:
• HM201
HM201 will be administered intravenously.
• Placebo
Placebo will be administered intravenously.
• HM201
HM201 will be administered intravenously.
• Placebo
Placebo will be administered intravenously.

Locations

Country	Name	City	State
Australia	Nucleus Network Pty Ltd	Herston	Queensland

Sponsors (2)

Lead Sponsor	Collaborator
Syneos Health	Himuka AM Pharma Corp.

Country where clinical trial is conducted

Australia, 

Outcome

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