Caplacizumab Single and Multiple Dose Study in Healthy Japanese and White Subjects.

Study Overview
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Brief Summary
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Primary objective: To assess the safety and tolerability of single ascending intravenous (i.v.) doses, a single subcutaneous (s.c.) dose of caplacizumab (Part I), and multiple s.c. doses of caplacizumab (Part II) in Japanese subjects. Secondary objectives: To compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles (total vWF:Ag concentration levels [vWF:Ag], coagulation factor VIII [FVIII:C], and ristocetin cofactor activity [RICO]) after single i.v. or s.c. administration of caplacizumab in Japanese and White subjects. To evaluate the immunogenicity of caplacizumab (anti-drug antibodies [ADA]) in Japanese subjects.

Official Title
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A Phase I Single Center, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Caplacizumab in Japanese and White Healthy Volunteers.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: Caplacizumab Dose 1 iv (single-dose)
* Biological: Caplacizumab Dose 2 iv (single-dose)
* Biological: Caplacizumab Dose 2 sc (single-dose)
* Biological: Caplacizumab Dose 2 sc (multiple-dose)
* Other: Placebo iv (single-dose)
* Other: Placebo sc (single-dose)
* Other: Placebo sc (multiple-dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between ≥18 kg/m² and <30 kg/m² at time of screening Body weight between ≥45 kg and <100 kg Baseline vWF:Ag between ≥60% and <170% (0.6-1.7 IU/mL) Exclusion Criteria: History of and/or any sign or symptom indicating current abnormal hemostasis or blood dyscrasia, including but not limited to thrombocytopenia, thrombocytopathy, thromboasthenia, hemophilia, von Willebrand's disease, vascular purpura, bleeding gums and/or frequent nose bleeding, easy/spontaneous bruises, meno- or metrorrhagia, history of gastrointestinal bleeding or excessive bleeding after minor injury such as shaving. Family history of congenital vascular malformation (e.g., Marfan's Syndrome) and/or bleeding disorder (e.g., hemophilia, von Willebrand's disease, Christmas disease) Any surgical intervention (including tooth extraction) or trauma within the 4 weeks preceding screening for the study or any planned surgical intervention during the participation in the study Treatment with vitamin K, direct oral anticoagulant (DOAC), warfarin, high dose heparin within 2 weeks before screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Japanese - Caplacizumab Dose 1 iv (SD)<br>Single dose (SD) of Caplacizumab Dose 1 administered intravenously (iv) to Japanese participants | Biological: Caplacizumab Dose 1 iv (single-dose)<br>* Single intravenous (iv) administration of Caplacizumab Dose 1<br>|
| Placebo Comparator: Group 1: Japanese - Placebo iv (SD)<br>Single dose (SD) of Placebo administered intravenously (iv) to Japanese participants | Other: Placebo iv (single-dose)<br>* Single intravenous (iv) administration of Placebo<br>|
| Experimental: Group 2: Japanese - Caplacizumab Dose 2 iv (SD)<br>Single dose (SD) of Caplacizumab Dose 2 administered intravenously (iv) to Japanese participants | Biological: Caplacizumab Dose 2 iv (single-dose)<br>* Single intravenous (iv) administration of Caplacizumab Dose 2<br>|
| Experimental: Group 2: Japanese - Placebo iv (SD)<br>Single dose (SD) of Placebo administered intravenously (iv) to Japanese participants | Other: Placebo iv (single-dose)<br>* Single intravenous (iv) administration of Placebo<br>|
| Experimental: Group 2: White - Caplacizumab Dose 2 iv (SD)<br>Single dose (SD) of Caplacizumab Dose 2 administered intravenously (iv) to White participants | Biological: Caplacizumab Dose 2 iv (single-dose)<br>* Single intravenous (iv) administration of Caplacizumab Dose 2<br>|
| Placebo Comparator: Group 2: White - Placebo iv (SD)<br>Single dose (SD) of Placebo administered intravenously (iv) to White participants | Other: Placebo iv (single-dose)<br>* Single intravenous (iv) administration of Placebo<br>|
| Experimental: Group 3: Japanese - Caplacizumab Dose 2 sc (SD)<br>Single dose (SD) of Caplacizumab Dose 2 administered subcutaneously (sc) to Japanese participants | Biological: Caplacizumab Dose 2 sc (single-dose)<br>* Single subcutaneous (sc) administration of Caplacizumab Dose 2<br>|
| Placebo Comparator: Group 3: Japanese - Placebo sc (SD)<br>Single dose (SD) of Placebo administered subcutaneously (sc) to Japanese participants | Other: Placebo sc (single-dose)<br>* Single subcutaneous (sc) administration of Placebo<br>|
| Experimental: Group 3: White - Caplacizumab Dose 2 sc (SD)<br>Single dose (SD) of Caplacizumab Dose 2 administered subcutaneously (sc) to White participants | Biological: Caplacizumab Dose 2 sc (single-dose)<br>* Single subcutaneous (sc) administration of Caplacizumab Dose 2<br>|
| Placebo Comparator: Group 3: White - Placebo sc (SD)<br>Single dose (SD) Placebo administered subcutaneously (sc) to White participants | Other: Placebo sc (single-dose)<br>* Single subcutaneous (sc) administration of Placebo<br>|
| Experimental: Group 4: Japanese - Caplacizumab Dose 2 sc (MD)<br>Multiple doses (MD) of Caplacizumab Dose 2 administered subcutaneously (sc) to Japanese participants | Biological: Caplacizumab Dose 2 sc (multiple-dose)<br>* Once daily subcutaneous (sc) administration of Caplacizumab Dose 2 during 7 consecutive days<br>|
| Placebo Comparator: Group 4: Japanese - Placebo sc (MD)<br>Multiple doses (MD) of Placebo administered subcutaneously (sc) to Japanese participants | Other: Placebo sc (multiple-dose)<br>* Once daily subcutaneous (sc) administration of Placebo during 7 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of treatment-emergent adverse events (Safety and Tolerability) |  | From signing of informed consent form until Day 28 (single-dose part) or Day 34 (multiple dose part) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: concentration of caplacizumab in plasma |  | From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part) | 
| Pharmacokinetics: concentration of caplacizumab in urine |  | From Day 1 to Day 4 (single dose part) or to Day 8 (multiple dose part) | 
| Pharmacodynamics as measured by Ristocetin cofactor activity in plasma |  | From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part) | 
| Pharmacodynamics as measured by von Willebrand factor antigen in plasma |  | From screening to Day 6 (single dose part) or to Day 12 (multiple dose part) | 
| Pharmacodynamics as measured by Factor VIII clotting activity in plasma |  | From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part) | 
| Immunogenicity as measured by the concentration of anti-caplacizumab antibodies in serum |  | From screening until Day 28 (single-dose part) or Day 34 (multiple dose part) |