Clinical trial NCT05088369: Assessment of the Safety, Tolerability, and Pharmacokinetic of HM201
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Crohn's Disease
Lead sponsor: Syneos Health
Sponsor class: OTHER
Collaborators: name: Himuka AM Pharma Corp.
First posted: 2021-10-21
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: SAD \& MAD study
Primary purpose: TREATMENT

Brief 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.

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number and percentage of treatment-emergent adverse event, serious adverse event and discontinuation.
timeFrame: Up to 15 days post last infusion for both SAD & MAD
Secondary outcomes:
measure: Plasma concentrations of HM201
timeFrame: SAD: Up to Day 15. MAD: Up to Day 36
measure: Pharmacokinetic assessment 1
timeFrame: SAD: Up to Day 15. MAD: Up to Day 36
measure: Pharmacokinetic assessment 2
timeFrame: SAD: Up to Day 15. MAD: Up to Day 36
measure: Pharmacokinetic assessment 3
timeFrame: SAD: Up to Day 15. MAD: Up to Day 36
measure: Pharmacokinetic assessment 4
timeFrame: MAD: Up to Day 36
measure: Pharmacokinetic assessment 5
timeFrame: SAD: Up to Day 15. MAD: Up to Day 36
measure: Pharmacokinetic assessment 6
timeFrame: SAD: Up to Day 15. MAD: Up to Day 36
measure: Pharmacokinetic assessment 7
timeFrame: SAD: Up to Day 15. MAD: Up to Day 36
measure: Pharmacokinetic assessment 8
timeFrame: SAD: Up to Day 15. MAD: Up to Day 36
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Nucleus Network Pty Ltd
state: Queensland
Study officials:
affiliation: Nucleus Network Pty Ltd.
name: Kristi McLendon, MD
role: PRINCIPAL_INVESTIGATOR
References: