Assessment of the Safety, Tolerability, and Pharmacokinetic of HM201

Sponsor
Syneos Health (Other)
Overall Status
Recruiting
CT.gov ID
NCT05088369
Collaborator
Himuka AM Pharma Corp. (Other)
68
1
4
12.6
5.4

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Early Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
68 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
SAD & MAD studySAD & MAD study
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
This study will be conducted as a double-blind study. All subjects and clinical personnel will involved in the collection, monitoring, revision, safety and adverse events will be blinded in regards to the subject's treatment assigned of HM201 or the HM201 placebo. All personnel affecting the outcome of the study's treatment assignment will be blinded.
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Nov 11, 2021
Anticipated Primary Completion Date :
Aug 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Plasma concentrations of HM201 [SAD: Up to Day 15. MAD: Up to Day 36]

    2. Pharmacokinetic assessment 1 [SAD: Up to Day 15. MAD: Up to Day 36]

      Area under the plasma concentration versus time curve (AUC)

    3. Pharmacokinetic assessment 2 [SAD: Up to Day 15. MAD: Up to Day 36]

      Peak Plasma Concentration (Cmax)

    4. Pharmacokinetic assessment 3 [SAD: Up to Day 15. MAD: Up to Day 36]

      Time of peak plasma concentration (Tmax)

    5. Pharmacokinetic assessment 4 [MAD: Up to Day 36]

      Concentration at the last planned timepoint prior to dosing (Ctrough)

    6. Pharmacokinetic assessment 5 [SAD: Up to Day 15. MAD: Up to Day 36]

      Mean residence time (MRT)

    7. Pharmacokinetic assessment 6 [SAD: Up to Day 15. MAD: Up to Day 36]

      Drug clearance (CL) & Clearance at steady state (CLss)

    8. Pharmacokinetic assessment 7 [SAD: Up to Day 15. MAD: Up to Day 36]

      Volume of distribution at steady state (Vss) & during terminal phase (VZ)

    9. Pharmacokinetic assessment 8 [SAD: Up to Day 15. MAD: Up to Day 36]

      Half life (T1/2)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Nucleus Network Pty Ltd Herston Queensland Australia 4006

    Sponsors and Collaborators

    • Syneos Health
    • Himuka AM Pharma Corp.

    Investigators

    • Principal Investigator: Kristi McLendon, MD, Nucleus Network Pty Ltd

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Syneos Health
    ClinicalTrials.gov Identifier:
    NCT05088369
    Other Study ID Numbers:
    • HM201-AUS-001
    First Posted:
    Oct 21, 2021
    Last Update Posted:
    Apr 27, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 27, 2022