Clinical trial NCT01439971: Phase 1 Safety, Pharmacokinetics And Pharmacodynamics Study Of Recombinant Factor VIIa Variant (813d) In Adult Subjects With Hemophilia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia A
Keywords: Phase 1
Safety
Pharmacokinetic
Pharmacodynamic
Lead sponsor: Catalyst Biosciences
Sponsor class: INDUSTRY
First posted: 2011-09-23
Enrollment: 29
Sex: MALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The was an ascending dose trial with one open label treatment, intervention model was sequential dose escalation.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Day 2, Day 3, and Day 15
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Day 2, Day 3, and Day 15
measure: Change From Baseline in Body Temperature
timeFrame: Baseline, Day 2, Day 3, and Day 15
measure: Change From Baseline in Respiration Rate
timeFrame: Baseline, Day 2, Day 3, and Day 15
measure: Change From Baseline in Supine Pulse Rate
timeFrame: Baseline, Day 2, Day 3, and Day 15
measure: Number of Participants With Changes Since Previous Physical Examination
timeFrame: Baseline (Day 0), Day 1, Day 2, Day 3, Day 15
measure: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Baseline through Day 15
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs (Except Hemophilia AEs)
timeFrame: Baseline through Day 60
measure: Number of Participants With Treatment-Emergent Hemophilia AEs and Withdrawals Due to Hemophilia AEs
timeFrame: Baseline through Day 60
measure: Number of Treatment-Emergent AEs and SAEs by Severity (Except Hemophilia AEs)
timeFrame: Baseline through Day 60
measure: Number of Treatment-Emergent Hemophilia AEs by Severity
timeFrame: Baseline through Day 60
measure: Number of Participants With Treatment-Emergent Abnormal Troponin-T Levels by Magnitude
timeFrame: Baseline through Day 15
measure: Number of Participants With Treatment-Emergent Abnormal Anti-Thrombin III (ATIII) Levels by Magnitude
timeFrame: Baseline through Day 3
measure: Number of Participants With Treatment-Emergent Abnormal Tissue Factor Pathway Inhibitor (TFPI) Levels by Magnitude
timeFrame: Baseline through Day 3
measure: Number of Participants With Treatment-Emergent Laboratory Test Abnormalities (Normal Baseline)
timeFrame: Baseline through Day 15
measure: Number of Participants With Clinically Significant Laboratory Abnormalities Meeting Stopping Criteria
timeFrame: Baseline through Day 15
measure: Number of Participants With Positive Immune Response (Anti-Drug Antibodies [ADA], PF-05280602 Inhibitor, Factor VIIa Inhibitor, Factor VII Inhibitor, and Depletion of Factor VII Activity)
timeFrame: Baseline through Day 60
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Terminal Elimination Half-Life (t1/2)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Incremental Recovery (IncRec)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Mean Residence Time (MRT)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Clearance (CL)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Day 1 (pre-dose and 5 min, 10 min, 20 min, 30 min, 1 hr, 3 hr, 6 hr, 9 hr, and 12 hrs post-dose), Day 2 (24 hrs post-dose), Day 3 (48 hrs post-dose)
measure: Maximum Mean Decrease From Baseline in Prothrombin Time (PT)
timeFrame: Baseline through Day 15
measure: Maximum Mean Decrease From Baseline in Activated Partial Thromboplastin Time (aPTT)
timeFrame: Baseline through Day 15
measure: Maximum Mean Increase From Baseline in Thrombin Anti-Thrombin (TAT) Complexes
timeFrame: Baseline through Day 3
measure: Maximum Mean Increase From Baseline in Prothrombin Fragments 1+2
timeFrame: Baseline through Day 3
measure: Maximum Mean Increase From Baseline in D-Dimers
timeFrame: Baseline through Day 15
measure: Maximum Mean Increase From Baseline in Endogenous Thrombin Potential (ETP)
timeFrame: Baseline through Day 3
measure: Maximum Mean Decrease From Baseline in Thrombin Generation Lag Time
timeFrame: Baseline through Day 3
measure: Maximum Mean Increase From Baseline in Peak Thrombin Generation
timeFrame: Baseline through Day 3
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Doernbecher Children's Hospital
state: Oregon
city: Portland
country: United States
facility: OHSU Investigational Pharmacy
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: CTRC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Comprehensive Hemophilia Program - Center for Blood Disorders
state: Pennsylvania
city: Bruxelles
country: Belgium
facility: Pfizer Clinical Research Unit
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Altalanos Orvostudomanyi Kar/ I.sz. Belgyogyaszati Klinika
city: Castelfranco Veneto (TV)
country: Italy
facility: Dipartimento di Medicina Clinica 1-Centro Regionale per le Malattie del Sangue
city: Castelfranco Veneto - Treviso
country: Italy
facility: Servizio Farmacia- Ospedale Castelfranco Veneto
city: Milano
country: Italy
facility: Centro Emofilia e Trombosi "Angelo Bianchi Bonomi" U.O.S. Dipartimentale per la Diagnosi e la Terapi
city: Milano
country: Italy
facility: Servizio Farmacia Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
city: Vicenza
country: Italy
facility: Centro Malattie Emorragiche e Trombotiche - Ematologia
city: Vicenza
country: Italy
facility: Farmacia Ospedaliera Ospedale San Bortolo
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust
city: Port Elizabeth
country: South Africa
facility: Phoenix Pharma (Pty) Ltd
state: Eastern Cape
city: Izmir
country: Turkey
facility: Ege University Tip Fakultesi
city: London
country: United Kingdom
facility: Royal Free Hampstead NHS Trust, Royal Free Hospital
city: London
country: United Kingdom
facility: Haematology Department
city: Manchester
country: United Kingdom
facility: Central Manchester Universtiy Hospitals NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: