Clinical trial NCT03172208: Caplacizumab Single and Multiple Dose Study in Healthy Japanese and White Subjects.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Ablynx, a Sanofi company
Sponsor class: INDUSTRY
First posted: 2017-06-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: The number of treatment-emergent adverse events (Safety and Tolerability)
timeFrame: From signing of informed consent form until Day 28 (single-dose part) or Day 34 (multiple dose part)
Secondary outcomes:
measure: Pharmacokinetics: concentration of caplacizumab in plasma
timeFrame: From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part)
measure: Pharmacokinetics: concentration of caplacizumab in urine
timeFrame: From Day 1 to Day 4 (single dose part) or to Day 8 (multiple dose part)
measure: Pharmacodynamics as measured by Ristocetin cofactor activity in plasma
timeFrame: From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part)
measure: Pharmacodynamics as measured by von Willebrand factor antigen in plasma
timeFrame: From screening to Day 6 (single dose part) or to Day 12 (multiple dose part)
measure: Pharmacodynamics as measured by Factor VIII clotting activity in plasma
timeFrame: From Day -1 to Day 6 (single dose part) or to Day 12 (multiple dose part)
measure: Immunogenicity as measured by the concentration of anti-caplacizumab antibodies in serum
timeFrame: From screening until Day 28 (single-dose part) or Day 34 (multiple dose part)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Investigator Site
state: California
Study officials:
affiliation: Ablynx, a Sanofi company
name: Ablynx Clinical Department
role: STUDY_DIRECTOR
References: