A randomized, participant and investigator-blinded, placebo-controlled, single ascending intravenous and single subcutaneous dose study to assess the safety, tolerability and pharmacokinetics of CMK389 in Japanese healthy participants

JRCT ID: jRCT2071210115

Registered date:21/01/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Japanese healthy participants
• Date of first enrollment: 05/02/2022
• Target sample size: 32
• Study type: Interventional

Intervention(s)

Cohort 1
- Single i.v. infusion of 3 mg/kg CMK389
- Single i.v. infusion of CMK389 placebo arm
Cohort 2
- Single i.v. infusion of 10 mg/kg CMK389
- Single i.v. infusion of CMK389 placebo arm
Cohort 3
- Single i.v. infusion of 30 mg/kg CMK389
- Single i.v. infusion of CMK389 placebo arm
Cohort 4
- Single s.c. injection of 300 mg CMK389
- Single s.c. injection of CMK389 placebo arm

Outcome(s)

• Primary Outcome: All safety endpoints [i.e., vital signs, ECG parameters, clinical laboratories, and AEs, including SAEs] up to and including the End of Study (EOS) visit

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 65age old
• Gender: Both

Include criteria

1. Written informed consent must be obtained before any assessment is performed.
2. Japanese healthy participants 20 to 65 years of age included, and in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at screening and baseline.
3. Able to communicate well with the investigator, to understand and comply with the requirements of the study.
4. Participants must weigh at least 45 kg (female) or 50 kg (male) to participate in the study, and must have a BMI within the range of 18-30 kg/m2 at screening.
5. At screening and baseline, vital signs (body temperature, systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the participant has rested at least 3 minutes. Sitting vital signs should be within the following ranges:
- Axillary body temperature between 35.0-37.5 degree Celsius
- Systolic blood pressure, 90-139 mm Hg
- Diastolic blood pressure, 40-89 mm Hg
- Pulse rate, 40-90 bpm

Exclude criteria

1. Participants who are not capable of giving consent, persons depending on the sponsor, investigator or site as well as persons who have been committed to an institution by way of official or judicial order.
2. Use of any prescription drugs or herbal supplements within 4 weeks prior to initial dosing, and/or over-the-counter (OTC) medication or dietary supplements (vitamins included) within 2 weeks prior to initial dosing.
3. Use of other investigational drugs at the time of screening, or within a period corresponding to less than 5 half-lives of the drug before screening, or within 30 days, whichever is longer.
4. Significant illness, including infectious diseases that has not resolved within 2 weeks prior to baseline, or positive SARS-CoV-2 test result at screening, or contact with a known case of COVID-19 infection in the 2 weeks prior to baseline.
5. COVID-19 vaccination in progress (plan to receive or in between the first and second dose) at baseline, or within 3 weeks of the last dose (i.e. completion of the vaccination).
6. Receipt of live/attenuated vaccine within a 1 month period before dose of CMK389 (Day 1).
7. History of hepatitis B or hepatitis C or serologic evidence for viral hepatitis. A positive Hepatitis B virus surface antigen (HBsAg) test at screening excludes a participant. Participants with a positive Hepatitis C virus (HCV) antibody test should be excluded.
8. History of immunodeficiency diseases, including a positive Human immunodeficiency virus (HIV) (antibodies to HIV Type 1 and/or Type 2 and confirmatory test) test result at screening
9. A positive syphilis test result at Screening.
10. Any clinically relevant abnormalities on hematology and clinical chemistry at screening or baseline.
11. Any history or presence of significant hematological abnormalities or immunodeficiency or any condition that might compromise the immune system (e.g., immunosuppressive treatment)
12. Any history of drug or alcohol abuse or history of recreational cannabis use within 4 weeks prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening.
13. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin) within 5 years of screening, regardless of whether there is evidence of local recurrence or metastases.
14. Lifetime history of hypersensitivity or allergy to any of the study treatments or excipients or to drugs of similar chemical classes.
15. Smokers (use of tobacco/nicotine products within 3 months of dosing). Urine cotinine levels will be measured during screening and at baseline for all participants.
16. Any surgical or medical condition which might put the participant at risk in case of participation in the study. The Investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence of any of the following: At screening or baseline
- Lipase and/or amylase must not exceed the 1.5 x upper limit of normal (ULN)
- Liver disease or liver injury as indicated by abnormal liver function tests (LFT) (as defined below):
- Any of the following single parameters in serum of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), gamma-GT, alkaline phosphatase (ALP) or bilirubin must not exceed 1.5 x ULN.
- Any elevation above ULN of more than one parameter of ALT, AST, gamma-GT, ALP or serum bilirubin will exclude a participant from participation in the study.
- History of renal injury / renal disease or presence of impaired renal function as indicated by any elevation above ULN of creatinine and/or BUN values, or the presence of abnormal urinary constituents (e.g., albuminuria)
- Evidence of urinary obstruction or difficulty in voiding
17. Lifetime history or current diagnosis of cardiac or cardiac repolarization abnormalities indicating significant risk of safety for participating in the study
18. The ECG abnormalities at screening or baseline
19. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
20. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the giving birth, confirmed by a positive hCG laboratory test
21. Women of child-bearing potential (WOCBP) (see definition below), unless they are using highly effective methods of contraception until EOS.

Related Information

• Primary Sponsor: Yamada Hiroyuki