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

NCT03172208 | Completed Phase 1 FDA Drug

• 1 other identifier: ALX0681-C103
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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)

Study Arms (12)

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

EXPERIMENTAL

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

Biological: Caplacizumab Dose 1 iv (single-dose)

Group 1: Japanese - Placebo iv (SD)

PLACEBO COMPARATOR

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

Other: Placebo iv (single-dose)

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

EXPERIMENTAL

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

Biological: Caplacizumab Dose 2 iv (single-dose)

Group 2: Japanese - Placebo iv (SD)

EXPERIMENTAL

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

Other: Placebo iv (single-dose)

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

EXPERIMENTAL

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

Biological: Caplacizumab Dose 2 iv (single-dose)

Group 2: White - Placebo iv (SD)

PLACEBO COMPARATOR

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

Other: Placebo iv (single-dose)

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

EXPERIMENTAL

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

Biological: Caplacizumab Dose 2 sc (single-dose)

Group 3: Japanese - Placebo sc (SD)

PLACEBO COMPARATOR

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

Other: Placebo sc (single-dose)

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

EXPERIMENTAL

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

Biological: Caplacizumab Dose 2 sc (single-dose)

Group 3: White - Placebo sc (SD)

PLACEBO COMPARATOR

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

Other: Placebo sc (single-dose)

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

EXPERIMENTAL

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

Biological: Caplacizumab Dose 2 sc (multiple-dose)

Group 4: Japanese - Placebo sc (MD)

PLACEBO COMPARATOR

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

Other: Placebo sc (multiple-dose)

Interventions

Caplacizumab Dose 1 iv (single-dose) BIOLOGICAL

Single intravenous (iv) administration of Caplacizumab Dose 1

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

Caplacizumab Dose 2 iv (single-dose) BIOLOGICAL

Single intravenous (iv) administration of Caplacizumab Dose 2

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

Caplacizumab Dose 2 sc (single-dose) BIOLOGICAL

Single subcutaneous (sc) administration of Caplacizumab Dose 2

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

Caplacizumab Dose 2 sc (multiple-dose) BIOLOGICAL

Once daily subcutaneous (sc) administration of Caplacizumab Dose 2 during 7 consecutive days

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

Placebo iv (single-dose) OTHER

Single intravenous (iv) administration of Placebo

Group 1: Japanese - Placebo iv (SD); Group 2: Japanese - Placebo iv (SD); Group 2: White - Placebo iv (SD)

Placebo sc (single-dose) OTHER

Single subcutaneous (sc) administration of Placebo

Group 3: Japanese - Placebo sc (SD); Group 3: White - Placebo sc (SD)

Placebo sc (multiple-dose) OTHER

Once daily subcutaneous (sc) administration of Placebo during 7 consecutive days

Group 4: Japanese - Placebo sc (MD)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ablynx, a Sanofi company: lead

Study Sites (1)

Investigator Site

Glendale, California, 91206, United States

Location

Study Officials

• Ablynx Clinical Department

  Ablynx, a Sanofi company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2017
• First Posted: June 1, 2017
• Study Start: June 5, 2017
• Primary Completion: October 19, 2017
• Study Completion: October 19, 2017
• Last Updated: November 14, 2017

Record last verified: 2017-11

Locations

US (1)