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

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: Caplacizumab Dose 1 iv (single-dose); Other: Placebo iv (single-dose); Biological: Caplacizumab Dose 2 iv (single-dose); Biological: Caplacizumab Dose 2 sc (single-dose); Other: Placebo sc (single-dose); Biological: Caplacizumab Dose 2 sc (multiple-dose); Other: Placebo sc (multiple-dose)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Investigator site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

12

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Ablynx

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2017
• Primary Completion (Actual): October 19, 2017
• Study Completion (Actual): October 19, 2017

Study Registration Dates

• First Submitted: May 29, 2017
• First Submitted That Met QC Criteria: May 31, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): November 14, 2017
• Last Update Submitted That Met QC Criteria: November 9, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: ALX0681-C103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No