Clinical trial NCT02974855: PF-06741086 Multiple Dose Study in Severe Hemophilia
Official title: A MULTICENTER, OPEN-LABEL, MULTIPLE ASCENDING DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF SUBCUTANEOUS OR INTRAVENOUS PF-06741086 IN SUBJECTS WITH SEVERE HEMOPHILIA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia A or B
Keywords: hemophilia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-11-29
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: This study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of multiple subcutaneous and/or intravenous doses of PF-06741086 in subjects with severe hemophilia.


Eligibility criteria: Inclusion Criteria:

* Severe hemophilia A or B (Factor VIII or Factor IX activity ≤ 1%), including patients with inhibitors to Factor VIII or Factor IX
* Episodic (on-demand) treatment regimen prior to screening
* At least 6 acute bleeding episodes during the 6-month period prior to screening

Exclusion Criteria:

* Known coronary artery, thrombotic, or ischemic disease
* Currently receiving treatment for acute bleeding episodes with APCC and cannot substitute treatment with rFVIIa

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Study Day 1 to Day 113 Visit
measure: Number of Participants Discontinued From Study Due to TEAEs
timeFrame: Study Day 1 to Day 113 Visit
measure: Number of Participants With Abnormal Laboratory Findings-Hematology
timeFrame: Baseline to Study Day 113 Visit
measure: Number of Participants With Abnormal Laboratory Findings-Clinical Chemistry
timeFrame: Baseline to Study Day 113
measure: Number of Participants With Abnormal Laboratory Findings-Urinalysis
timeFrame: Baseline to Study Day 113 Visit
measure: Change From Baseline for Globulin by Dose Cohort
timeFrame: Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113.
measure: Change From Baseline for Prothrombin International Normalized Ratio (PT/INR) by Dose Cohort
timeFrame: Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113.
measure: Change From Baseline for Activated Partial Thromboplastin Time (aPTT) by Dose Cohort
timeFrame: Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113.
measure: Change From Baseline for Fibrinogen by Dose Cohort
timeFrame: Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113.
measure: Change From Baseline for Antithrombin III by Dose Cohort
timeFrame: Baseline, Study Day 8, 15, 22 and 29.
measure: Change From Baseline for Troponin I by Dose Cohort
timeFrame: Baseline, Study Day 8, 15, 22, 29, 57 and 85.
measure: Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
timeFrame: Baseline to Study Day 113 Visit
measure: Number of Participants With Electrocardiogram (ECG) Change Meeting Pre-specified Criteria
timeFrame: Baseline to Study Day 29 Visit.
measure: Number of Participants With Clinically Significant Changes in Physical Examination Findings
timeFrame: Baseline to Study Day 113 Visit
measure: Number of Participants With Infusion and Injection Site Reactions
timeFrame: Baseline to Study Day 113 Visit
Secondary outcomes:
measure: Annualized Bleeding Rate (ABR)
timeFrame: Pre-treatment: within 6 months prior to study enrollment; On-study: Day 1 to 9 days after the last dose (Day 78)
measure: Plasma PF-06741086 Concentrations
timeFrame: pre-dose on Study Day 1, 24hours (h), 72h post Study Day 1 dosing, pre-dose on Study Day 8, 15 and 22, pre-dose on Study Day 29, 24h, 96h post Study Day 29 dosing, pre-dose on Study Day 57, 168h, 840h post Study Day 57 dosing
measure: Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06741086
timeFrame: Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing
measure: Maximum Plasma Concentration (Cmax) of PF-06741086
timeFrame: Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing
measure: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06741086
timeFrame: Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing
measure: Time to Reach Maximum Plasma Concentration (Tmax) of PF-06741086
timeFrame: Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing
measure: Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of PF-06741086
timeFrame: Pre-dose on Day 29, 24 and 96 hours post Day 29 dosing
measure: Apparent Clearance After Oral Dose (CL/F) of PF-06741086
timeFrame: Pre-dose on Day 29, 24 and 96 hours post Day 29 dosing
measure: Change From Baseline in Total Tissue Factor Pathway Inhibitor (TFPI)
timeFrame: Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113
measure: Change From Baseline in Thrombin Generation (TGA) Lag Time
timeFrame: Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113
measure: Change From Baseline in Thrombin Generation (TGA) Peak
timeFrame: Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113
measure: Change From Baseline in Endogenous Thrombin Generation (TGA) Potential
timeFrame: Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113
measure: Change From Baseline in Prothrombin Fragments 1 + 2
timeFrame: Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113
measure: Change From Baseline in D-Dimer
timeFrame: Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113
measure: Change From Baseline in Dilute Prothrombin Time
timeFrame: Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113
measure: Number of Participants Who Tested Positive for Anti-PF-06741086 Antibody (ADA)
timeFrame: Baseline up to Study Day 113
measure: Number of Participants Who Tested Positive for Neutralizing Antibody (NAb)
timeFrame: Baseline up to Study Day 113
Other outcomes:
Locations:
city: Aurora
country: United States
facility: UC Denver Hemophilia and Thrombosis Center - Pharmacy
state: Colorado
city: Aurora
country: United States
facility: UC Denver Hemophilia and Thrombosis Center
state: Colorado
city: Chicago
country: United States
facility: Pharmacy
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Santiago
country: Chile
facility: Hospital Dr. Sotero del Rio
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb
city: Gdansk
country: Poland
facility: Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne
city: Port Elizabeth
country: South Africa
facility: Phoenix Pharma (Pty) Ltd
state: Eastern CAPE
city: Johannesburg
country: South Africa
facility: Haemophilia Comprehensive Care Centre
state: Gauteng
city: Zurich
country: Switzerland
facility: UniversitatsSpital Zurich, Klinik fur Hamatologie
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Mahlangu JN, Lamas JL, Morales JC, Malan DR, Salek SZ, Wang M, Boggio LN, Hegemann I, Mital A, Cardinal M, Zhu T, Sun P, Arkin S. A phase 1b/2 clinical study of marstacimab, targeting human tissue factor pathway inhibitor, in haemophilia. Br J Haematol. 2023 Jan;200(2):229-239. doi: 10.1111/bjh.18420. Epub 2022 Aug 23.