A Phase 1 Safety, Pharmacokinetics And Pharmacodynamics Study Of PF-05280602, A Recombinant Factor VIIa Variant (813d), In Adult Subjects With Hemophilia A Or B

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01439971
First received: August 26, 2011
Last updated: May 11, 2015
Last verified: May 2015
  Purpose

This study hypothesizes that the study drug, PF-05280602 (at the selected doses) will be safe to administer to subjects with severe Hemophilia A or B with or without inhibitors and will demonstrate evidence of hemostatic activity. This is supported by the preclinical findings in hemophilic animal models.


Condition Intervention Phase
Hemophilia A
Biological: PF-05280602
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Ascending Single Dose Study To Evaluate The Safety, Tolerability And Pharmacokinetics/Pharmacodynamics Of Pf-05280602, A Recombinant Factor Viia Variant (813d), In Adult Hemophilia A And B Subjects With Or Without Inhibitors

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Incdence of subjects wtih treatment emergent adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of of subjects with treatment emergent hemophilia adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of subjects with treatment emergent serious adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- blood pressure [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's ECG [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's physical examination [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for Tropin T levels [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for Troponin T levels [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of an immune response [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for Anti-Thrombin III [ Time Frame: Within 3 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for Tissue Factor Pathway Inhibitor [ Time Frame: Within 3 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Number of subjects with clinically significant changes from baseline in their fibrinogen [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- weight [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- temperature [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- respiration rate [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Changes from baseline in patient's vital signs- pulse rate [ Time Frame: Baseline, Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Severity of subjects wtih treatment emergent adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Severity of of subjects with treatment emergent hemophilia adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Severity of subjects with treatment emergent serious adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Withdrawals due to treatment emergent adverse events [ Time Frame: Within 60 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Withdrawals due to treatment emergent hemophilia events [ Time Frame: Within 60 Day of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for hematology [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for hematology [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for chemistry [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for chemistry [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for urinalysis [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for urinalysis [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for platelet count [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for platelet count [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for Anti-Thrombin III [ Time Frame: Within 3 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for Tissue Factor Pathway Inhibitor [ Time Frame: Within 3 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Incidence of treatment emergent clinical laboratory abnormalities for C-Reactive Protein [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]
  • Magnitude of treatment emergent clinical laboratory abnormalities for C-Reactive Protein [ Time Frame: Within 15 Days of Dosing ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, Cmax [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, area under the curve (AUC last) [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, terminal half-life [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, recovery [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Pharmacodynamic (Hematologic) activity as measured by the Prothrombin Time [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the activated partial thrombinplastin time [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the thrombin antithrombin complexes [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by the prothrombin fragments 1+2 [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by D-Dimers [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic (Hematologic) activity as measured by thrombin generation [ Time Frame: Through Day 15 Post Dosing ] [ Designated as safety issue: Yes ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, area under the curve (AUC inf) [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, mean residence time [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, Vss [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, clearance [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]
  • Factor VIIa concentration in subject plasma as measured by FVIIa PK assay, Tmax [ Time Frame: Through Day 3 Post Dosing ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: December 2011
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Biological: PF-05280602
4.5 micrograms per kilogram of PF-05280602, IV infusion, single dose
Experimental: 2 Biological: PF-05280602
9.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
Experimental: 3 Biological: PF-05280602
18.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
Experimental: 4 Biological: PF-05280602
30.0 micrograms per kilogram of PF-05280602, IV infusion, single dose

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male subjects 18 to <65 years old with severe hemophilia A or B with or without inhibitors to FVIII or FIX.
  • Subjects is willing and able to comply with the mandatory washout periods prior to screening and prior to dosing and through 48 hours post dosing. At screening this includes a washout of FIX for 96 hours and FVIII for 72 houts. At dosing this includes a washout of FIX for 96 hours and FVIII and other hemostatic agents for 72 hours through 48 hours post dosing.
  • Subjects must agree and commit to using a a highly effective method of birth control from the time of screening through four weeks after study drug administration.

Exclusion Criteria:

  • Presence of a bleeding disorder in addition to hemophilia A or B.
  • Regular, concomitant therapy with immunomodulating drugs (eg, intravenous immunoglobulin, and routine systemic corticosteroids).
  • History of coronary artery disease, thrombolic disease or diagnosis of prothrombic disorder.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01439971

Locations
United States, California
University of California San Diego medical center
San Diego, California, United States, 92103
United States, Connecticut
New Haven Clinical Research Unit
New Haven, Connecticut, United States, 06511
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Ohio
Cincinnati Children¿s Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Oregon
Doernbecher Children's Hospital
Portland, Oregon, United States, 97239
OHSU Investigational Pharmacy
Portland, Oregon, United States, 97239
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
CTRC
Philadelphia, Pennsylvania, United States, 19104
Penn Comprehensive Hemophilia Program - Center for Blood Disorders
Philadelphia, Pennsylvania, United States, 19104
Belgium
Pfizer Clinical Research Unit
Bruxelles, Belgium, B-1070
Hungary
Semmelweis Egyetem Altalanos Orvostudomanyi Kar/ I.sz. Belgyogyaszati Klinika
Budapest, Hungary, 1083
Italy
Ospedale Civile
Castelfranco Veneto, Treviso, Italy, 31033
Dipartimento Transfusionale ed Immunologia Centro Regionale per le Malattie del Sangue
Castelfranco Veneto, Italy, 31033
Servizio Farmacia- Ospedale Castelfranco Veneto
Castelfranco Veneto - Treviso, Italy, 31033
Centro Emofilia e Trombosi "Angelo Bianchi Bonomi"
Milano, Italy, 20122
Servizio Farmacia, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Milano, Italy, 20122
Centro Malattie Emorragiche e Trombotiche - Ematologia
Vicenza, Italy, 36100
Farmacia Ospedaliera Ospedale San Bortolo
Vicenza, Italy, 36100
New Zealand
Christchurch Clinical Studies Trust (CCST)
Christchurch, New Zealand, 08011
South Africa
Phoenix Pharma (Pty) Ltd
Port Elizabeth, Eastern Cape, South Africa, 6001
Turkey
Ege University
Bornova/Izmir, Turkey, 35100
United Kingdom
Haematology Department
London, United Kingdom, W12 0HS
Royal Free Hampstead NHS Trust, Royal Free Hospital
London, United Kingdom, NW3 2QG
Central Manchester Universtiy Hospitals NHS Foundation Trust
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01439971     History of Changes
Other Study ID Numbers: B3051001, 2011-002170-23
Study First Received: August 26, 2011
Last Updated: May 11, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Phase 1
Safety
Pharmacokinetic
Pharmacodynamic

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on May 26, 2015