A Phase 1 single ascending study in healthy Caucasian and Japanese Adult subjects to evaluate the Safety, Tolerability, and Pharmacokinetics of CSL346.

A Phase 1, Randomized, Double-blind, Placebo-controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CSL346 in Healthy Caucasian and Japanese Adult Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12617001554358

Enrollment

Registered

2017-11-15

Start date

2017-11-13

Completion date

2019-02-04

Last updated

2019-09-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

The purpose of this study is to characterize the safety and tolerability of single ascending doses of CSL346 following intravenous (IV) administration in healthy subjects. This is a 3-part first-in-human (FIH) study. Part A is a randomized, double-blind, placebo-controlled, single ascending intravenous (IV) dose protocol to be implemented in healthy Caucasian subjects. Part B is a single ascending IV dose escalation protocol which will test selected doses from Part A in healthy Japanese subjects. Part C is a single ascending dose escalation protocol which will test the subcutaneous (SC) administration of selected doses in Caucasian, and, if needed, Japanese subjects.

Interventions

Single intravenous infusion or subcutaneous injection of sterile solution for injection containing CSL346. Cohort A1: 0.1 mg/kg CSL346 or placebo; Cohort A2: 0.3 mg/kg CSL346 or placebo; Cohort A3: 1.0 mg/kg CSL346 or placebo; Cohort A4: 3 mg/kg CSL346 or placebo; Cohort A5: 10 mg/kg CSL346 or placebo; Cohort A6: (Optional) Additional dose, may be tested provided the dose is not expected to exceed predicted serum CSL346 Cmax of 3605 µg/mL and AUC0-168 of 297500 µg hr/mL Cohort B1 through B4: Part B procedures will mirror Part A, but without the use of a sentinel group. Up to 4 dose levels of CSL346 will be studied in a total of approximately 32 subjects. Cohorts C1-C2: In Part C of the study, the doses to be administered will be equivalent to doses previously administered by IV infusion. single ascending-doses of CSL346 will be administered by subcutaneous injection or infusion in up to 2 cohorts of healthy, adult, Caucasian subjects. SC administration will be evaluated at two dose levels: 'low dose' and 'high dose.' The Sponsor, in consultation with the SRC, will decide if sentinel subjects should be included in Part C.

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Treatment

Masking

Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

20 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

PART A: 1. Healthy caucasian male or female subject aged 20 to 55 years. 2. Male subjects and their female partners who are of childbearing potential must be using 2 highly effective forms of birth control (1 of which must be a barrier method) starting at Screening and through 90 days after the IV infusion of IP unless (a)-The male subject has undergone effective surgical sterilization prior to entering the clinical study, and/or (b)-The female sexual partner(s) of male subject has undergone effective surgical sterilization prior to the subject entering the clinical study or is (are) post-menopausal. 3. Healthy, as judged by the investigator, with a clinical assessment to include medical history, physical examination, vital signs, ECG, and clinical laboratory tests with no clinically important findings. 4. Have a body mass index (BMI) of 18 to 30 kg/m2 and weight > 50 kg. PART B: (In addition to inclusion criteria for PART A).1. Must be first generation Japanese, born in Japan and has not lived outside of Japan for greater than 10 years. PART C: (In addition to inclusion criteria items 2-4 for PART A). 1. Must be Caucasian or first generation Japanese.

Exclusion criteria

1. History of any clinically significant disease or disorder 2. Any positive result on screening for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (anti-HAV; IgM), hepatitis C virus antibodies (anti-HCV) or human immunodeficiency virus (HIV)-1 and/or -2 antibodies 3. Medical history of heart disease or any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG 4. History of alcohol, drug, or medication abuse within 1 year of providing informed consent 5. Smokers, those who have smoked or used tobacco products within 6 months prior to providing informed consent 6. Known or suspected hypersensitivity to CSL346, or to any excipients of CSL346 7. Women of childbearing potential 8. The subject has participated in any other investigational study drug trial within 30 days (or 5 half-lives, whichever is longer) or, has participated in more than 3 clinical studies involving the administration of an investigational agent within the last 12 months prior to the 1st dose of investigational product (IP) 9. The subject has a history of significant blood loss or has donated more than 500 mL within 90 days prior to the 1st dose of IP 10. Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis results as judged by the investigator and/or sponsor.

Outcome results