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

Ablynx

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Other: Placebo iv (single-dose); Other: Placebo sc (single-dose); Biological: Caplacizumab Dose 2 sc (multiple-dose); Biological: Caplacizumab Dose 1 iv (single-dose); Biological: Caplacizumab Dose 2 iv (single-dose); Biological: Caplacizumab Dose 2 sc (single-dose); Other: Placebo sc (multiple-dose)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03172208

ALX0681-C103

Details and patient eligibility

About

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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 12 patient groups, including a placebo group

Group 1: Japanese - Caplacizumab Dose 1 iv (SD)

Experimental group

Description:

Single dose (SD) of Caplacizumab Dose 1 administered intravenously (iv) to Japanese participants

Treatment:

Biological: Caplacizumab Dose 1 iv (single-dose)

Group 1: Japanese - Placebo iv (SD)

Placebo Comparator group

Description:

Single dose (SD) of Placebo administered intravenously (iv) to Japanese participants

Treatment:

Other: Placebo iv (single-dose)

Group 2: Japanese - Caplacizumab Dose 2 iv (SD)

Experimental group

Description:

Single dose (SD) of Caplacizumab Dose 2 administered intravenously (iv) to Japanese participants

Treatment:

Biological: Caplacizumab Dose 2 iv (single-dose)

Group 2: Japanese - Placebo iv (SD)

Experimental group

Description:

Single dose (SD) of Placebo administered intravenously (iv) to Japanese participants

Treatment:

Other: Placebo iv (single-dose)

Group 2: White - Caplacizumab Dose 2 iv (SD)

Experimental group

Description:

Single dose (SD) of Caplacizumab Dose 2 administered intravenously (iv) to White participants

Treatment:

Biological: Caplacizumab Dose 2 iv (single-dose)

Group 2: White - Placebo iv (SD)

Placebo Comparator group

Description:

Single dose (SD) of Placebo administered intravenously (iv) to White participants

Treatment:

Other: Placebo iv (single-dose)

Group 3: Japanese - Caplacizumab Dose 2 sc (SD)

Experimental group

Description:

Single dose (SD) of Caplacizumab Dose 2 administered subcutaneously (sc) to Japanese participants

Treatment:

Biological: Caplacizumab Dose 2 sc (single-dose)

Group 3: Japanese - Placebo sc (SD)

Placebo Comparator group

Description:

Single dose (SD) of Placebo administered subcutaneously (sc) to Japanese participants

Treatment:

Other: Placebo sc (single-dose)

Group 3: White - Caplacizumab Dose 2 sc (SD)

Experimental group

Description:

Single dose (SD) of Caplacizumab Dose 2 administered subcutaneously (sc) to White participants

Treatment:

Biological: Caplacizumab Dose 2 sc (single-dose)

Group 3: White - Placebo sc (SD)

Placebo Comparator group

Description:

Single dose (SD) Placebo administered subcutaneously (sc) to White participants

Treatment:

Other: Placebo sc (single-dose)

Group 4: Japanese - Caplacizumab Dose 2 sc (MD)

Experimental group

Description:

Multiple doses (MD) of Caplacizumab Dose 2 administered subcutaneously (sc) to Japanese participants

Treatment:

Biological: Caplacizumab Dose 2 sc (multiple-dose)

Group 4: Japanese - Placebo sc (MD)

Placebo Comparator group

Description:

Multiple doses (MD) of Placebo administered subcutaneously (sc) to Japanese participants

Treatment:

Other: Placebo sc (multiple-dose)