Healthy Volunteers
Conditions
Brief summary
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.
Interventions
BIOLOGICALCaplacizumab Dose 1 iv (single-dose)
Single intravenous (iv) administration of Caplacizumab Dose 1
BIOLOGICALCaplacizumab Dose 2 iv (single-dose)
Single intravenous (iv) administration of Caplacizumab Dose 2
BIOLOGICALCaplacizumab Dose 2 sc (single-dose)
Single subcutaneous (sc) administration of Caplacizumab Dose 2
BIOLOGICALCaplacizumab Dose 2 sc (multiple-dose)
Once daily subcutaneous (sc) administration of Caplacizumab Dose 2 during 7 consecutive days
OTHERPlacebo iv (single-dose)
Single intravenous (iv) administration of Placebo
OTHERPlacebo sc (single-dose)
Single subcutaneous (sc) administration of Placebo
OTHERPlacebo sc (multiple-dose)
Once daily subcutaneous (sc) administration of Placebo during 7 consecutive days
Sponsors
Ablynx, a Sanofi company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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) |
| Pharmacokinetics: concentration of caplacizumab in plasma | From Day -1 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) |
| 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) |
Countries
United States
Outcome results
None listed