Hemophilia APhase 1NCT01439971

Phase 1 Safety, Pharmacokinetics And Pharmacodynamics Study Of Recombinant Factor VIIa Variant (813d) In Adult Subjects With Hemophilia

A Phase 1 study testing PF-05280602 in people with Hemophilia A, run by Catalyst Biosciences at 23 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 64 years, men only
Conditions the study is for: Hemophilia A
What is being tested?: PF-05280602
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 23 sitesin 8 countries
Study dates: Dec 2011to Oct 2015
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 64 years
Men only
No healthy volunteers
Adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

23 sites in 8 countries.

Country

City, postcode or hospital

23 sites in 8 countries

United States9 sites

Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
New Haven Clinical Research Unit
New Haven, Connecticut, 06511
CTRC
Philadelphia, Pennsylvania, 19104
Penn Comprehensive Hemophilia Program - Center for Blood Disorders
Philadelphia, Pennsylvania, 19104
Doernbecher Children's Hospital
Portland, Oregon, 97239
OHSU Investigational Pharmacy
Portland, Oregon, 97239
Oregon Health & Science University
Portland, Oregon, 97239
University of California San Diego Medical Center
San Diego, California, 92103-8651

Other trials in United States

Italy6 sites

Servizio Farmacia- Ospedale Castelfranco Veneto
Castelfranco Veneto - Treviso, Italy, 31033
Dipartimento di Medicina Clinica 1-Centro Regionale per le Malattie del Sangue
Castelfranco Veneto (TV), Italy, 31033
Servizio Farmacia Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Milan, Italy, 20122
Centro Emofilia e Trombosi "Angelo Bianchi Bonomi" U.O.S. Dipartimentale per la Diagnosi e la Terapi
Milan, 20122
Farmacia Ospedaliera Ospedale San Bortolo
Vicenza, Italy, 36100
Centro Malattie Emorragiche e Trombotiche - Ematologia
Vicenza, 36100

Other trials in Italy

United Kingdom3 sites

Royal Free Hampstead NHS Trust, Royal Free Hospital
London, NW3 2QG
Haematology Department
London, W12 0HS
Central Manchester Universtiy Hospitals NHS Foundation Trust
Manchester, M13 9WL

Other trials in United Kingdom

Belgium1 site

Pfizer Clinical Research Unit
Brussels, B-1070

Other trials in Belgium

Hungary1 site

Semmelweis Egyetem Altalanos Orvostudomanyi Kar/ I.sz. Belgyogyaszati Klinika
Budapest, 1083

Other trials in Hungary

New Zealand1 site

Christchurch Clinical Studies Trust
Christchurch, New Zealand, 08011

Other trials in New Zealand

South Africa1 site

Phoenix Pharma (Pty) Ltd
Port Elizabeth, Eastern Cape, 6001

Other trials in South Africa

Turkey (Türkiye)1 site

Ege University Tip Fakultesi
Izmir, Turkey, 35100

Other trials in Turkey (Türkiye)

About this study

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

Conditions: Hemophilia A
Being tested: PF-05280602
Keywords: Phase 1, Safety, Pharmacokinetic, Pharmacodynamic
Medical subject headings: Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PF-05280602Biological
0.5 micrograms per kilogram of PF-05280602, IV infusion, single dose
PF-05280602Biological
4.5 micrograms per kilogram of PF-05280602, IV infusion, single dose
PF-05280602Biological
9.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
PF-05280602Biological
18.0 micrograms per kilogram of PF-05280602, IV infusion, single dose
PF-05280602Biological
30.0 micrograms per kilogram of PF-05280602, IV infusion, single dose

Study groups in NCT01439971
Study group	Role	What they receive
1	Experimental	Not described Receives: Biological: PF-05280602
2	Experimental	Not described Receives: Biological: PF-05280602
3	Experimental	Not described Receives: Biological: PF-05280602
4	Experimental	Not described Receives: Biological: PF-05280602
5	Experimental	Not described Receives: Biological: PF-05280602

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Supine blood pressure (BP) was measured with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mmHg) after 5 minutes of rest. The same arm (preferably the dominant arm) was to be used throughout the study.
Measured: Baseline, Day 2, Day 3, and Day 15
Change From Baseline in Body Weight
Measured: Baseline, Day 2, Day 3, and Day 15
Change From Baseline in Body Temperature
Body temperature was measured by mouth (oral) or ear (tympanic). A temperature greater than 38.5 degree Celsius was considered a fever.
Measured: Baseline, Day 2, Day 3, and Day 15
Change From Baseline in Respiration Rate
Respiration rate measured as respirations per minute (resp/min).
Measured: Baseline, Day 2, Day 3, and Day 15
Change From Baseline in Supine Pulse Rate
Change from baseline is the vital sign value at Day 2, Day 3, and Day 15 minus vital sign value at baseline.
Measured: Baseline, Day 2, Day 3, and Day 15
Number of Participants With Changes Since Previous Physical Examination
Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner. A complete physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, genitourinary, gastrointestinal, musculoskeletal, and neurological systems. The limited or abbreviated physical examination focused on general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms.
Measured: Baseline (Day 0), Day 1, Day 2, Day 3, Day 15
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
ECG findings of potential clinical concern were: PR interval greater than or equal to (>=)300 milliseconds (msec), >=25% increase from baseline for baseline values >200 msec, >=50% increase from baseline for baseline values less than or equal to (<=)200 msec; QRS complex >=140 msec or >=50% increase from baseline; QTcF interval (Fridericia's correction) >=450 msec or >=30 msec increase from baseline.
Measured: Baseline through Day 15
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs (Except Hemophilia AEs)
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 15 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Measured: Baseline through Day 60
Number of Participants With Treatment-Emergent Hemophilia AEs and Withdrawals Due to Hemophilia AEs
Hemophilia AEs included spontaneous (no known contributing factor) and traumatic (known or presumed contributing factor/reason) bleeding episodes.
Measured: Baseline through Day 60
Number of Treatment-Emergent AEs and SAEs by Severity (Except Hemophilia AEs)
AE severity were graded as mild, moderate, or severe. Mild severity AEs do not interfere with the participant's usual function. Moderate AEs interfere to some extent with the participant's usual function. Severe AEs interfere significantly with the participant's usual function.
Measured: Baseline through Day 60
Number of Treatment-Emergent Hemophilia AEs by Severity
Mild severity AEs do not interfere with the participant's usual function. Moderate AEs interfere to some extent with the participant's usual function. Severe AEs interfere significantly with the participant's usual function.
Measured: Baseline through Day 60
Number of Participants With Treatment-Emergent Abnormal Troponin-T Levels by Magnitude
Troponin-T is a cardiac marker for the evaluation of possible cardiovascular injury. Troponin-T levels of potential clinical concern are values >1.5 times the upper limit of normal (1.5X ULN) or >=2.5X ULN.
Measured: Baseline through Day 15
Number of Participants With Treatment-Emergent Abnormal Anti-Thrombin III (ATIII) Levels by Magnitude
ATIII is a protein in the blood that blocks abnormal blood clots from forming. Low levels of ATIII can cause abnormal blood clots. ATIII levels of potential clinical concern are values <1X LLN and >1X ULN.
Measured: Baseline through Day 3
Number of Participants With Treatment-Emergent Abnormal Tissue Factor Pathway Inhibitor (TFPI) Levels by Magnitude
TFPI is a polypeptide that can regulate blood coagulation. TFPI levels of potential clinical concern are values <1X LLN and >1X ULN.
Measured: Baseline through Day 3
Number of Participants With Treatment-Emergent Laboratory Test Abnormalities (Normal Baseline)
The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, creatinine, blood urea nitrogen [BUN], glucose, uric acid, sodium, potassium, chloride, bicarbonate, calcium, albumin, total protein, creatine kinase); urinalysis (urine white blood cell [WBC], urine RBC); other (troponin T).
Measured: Baseline through Day 15
Number of Participants With Clinically Significant Laboratory Abnormalities Meeting Stopping Criteria
Clinically significant findings for stopping rules are: hemoglobin <8 grams/deciliter (g/dL) or >20% decrease from normal baseline; WBC >20,000 cells/mm^3 or <1,500 decrease with normal baseline; platelets <100,000/mm^3 or >33% decrease from baseline; total bilirubin >1.5X ULN; AST or ALT >2.5X ULN; alkaline phosphatase >3X ULN; creatinine >1.5X baseline; BUN >31.0 mg/dL; glucose <0.6 or >1.5X reference range; uric acid > ULN; sodium >150 or <130 mEq/L; potassium >5.5 or <3.0 mEq/L; calcium >11.5 or <8.0 mg/dL; albumin <2.0 g/L; total protein <5.0 g/L; positive D-dimer at Day 15; PT prolonged by 3 seconds above baseline; ATIII < LLN and >20% decrease from baseline; troponin-T values above the reference range; fibrinogen <0.75X LLN or >25% decrease from baseline.
Measured: Baseline through Day 15
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)
Assays for the determination of a positive immune response was performed. An antibody immune response was defined as a confirmed post-treatment positive ELISA result in combination with a negative baseline sample ELISA result. Positive antibody immune responses to PF-05280602 by ELISA was evaluated for cross reactivity to NovoSeven RT and to Factor VII.
Measured: Baseline through Day 60

Secondary outcomes (17)

Maximum Observed Plasma Concentration (Cmax)
Measured: 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)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Measured: 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)
Terminal Elimination Half-Life (t1/2)
t1/2 is the time measured for the plasma concentration to decrease by one half.
Measured: 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)
Incremental Recovery (IncRec)
IncRec is the maximum rise in plasma concentration per administered dose.
Measured: 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)
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
AUCinf is area under the plasma concentration-time curve from time 0 extrapolated to infinite time.
Measured: 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)
Mean Residence Time (MRT)
MRT is AUMCinf/AUCinf, where AUMC is the area under the first moment curve.
Measured: 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)
Volume of Distribution at Steady State (Vss)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Measured: 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)
Clearance (CL)
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose is influenced by the fraction of the dose absorbed.
Measured: 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)
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measured: 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)
Maximum Mean Decrease From Baseline in Prothrombin Time (PT)
PT measures how long it takes blood to clot. Maximum mean decrease from baseline at any time point was reported.
Measured: Baseline through Day 15
Maximum Mean Decrease From Baseline in Activated Partial Thromboplastin Time (aPTT)
aPTT is a blood test that characterizes blood coagulation. Maximum mean decrease from baseline at any time point was reported.
Measured: Baseline through Day 15
Maximum Mean Increase From Baseline in Thrombin Anti-Thrombin (TAT) Complexes
TAT complex is a parameter of coagulation and fibrinolysis. The normal reference range of values for TAT is 1 to 4.1 mcg/L. Elevated TAT concentrations may signify predisposition to thrombosis. Maximum mean increase from baseline at any time point was reported.
Measured: Baseline through Day 3
Maximum Mean Increase From Baseline in Prothrombin Fragments 1+2
Prothrombin fragment 1+2 is a coagulation factor, released when prothrombin is cleaved by activated Factor X. Elevated plasma levels of prothrombin fragment 1+2 indicate high risk of thrombosis. Maximum mean increase from baseline at any time point was reported.
Measured: Baseline through Day 3
Maximum Mean Increase From Baseline in D-Dimers
D-dimer is an indicator of fibrin formation and its subsequent lysis and is a useful biomarker representing overall activation of blood coagulation. Maximum mean increase from baseline at any time point was reported.
Measured: Baseline through Day 15
Maximum Mean Increase From Baseline in Endogenous Thrombin Potential (ETP)
ETP was evaluated using a Thrombin Generation Assay (TGA), a validated automated ex-vivo assay that measures the ability of plasma to generate thrombin. Thrombin generation curves are generated and calculated using dedicated software. ETP is the area under the thrombin generation curve and represents the total amount of generated thrombin. Maximum mean increase from baseline at any time point was reported.
Measured: Baseline through Day 3
Maximum Mean Decrease From Baseline in Thrombin Generation Lag Time
The lag time is defined as the time to reach one sixth of the peak height and is a measure of the initiation phase. It is equivalent to the clotting time. Maximum mean decrease from baseline at any time point was reported.
Measured: Baseline through Day 3
Maximum Mean Increase From Baseline in Peak Thrombin Generation
The peak height is defined as the maximum thrombin concentration produced. Maximum mean increase from baseline at any time point was reported.
Measured: Baseline through Day 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2011Oct 2015

First posted23 Sep 2011 (estimated)
Study startDec 2011
Primary completionOct 2015
Study completionOct 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hemophilia AStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Sequential
Model description: The was an ascending dose trial with one open label treatment, intervention model was sequential dose escalation.
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01439971
Sponsor's protocol ID: B3051001
Other IDs: 2011-002170-23
Status last verified: Apr 2017
First submitted: 26 Aug 2011
Last updated: 12 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B

All Hemophilia A trials

Study at a glance

From the registry record, last updated by the sponsor on 12 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01439971
Acronym / sponsor ID: B3051001
Conditions: Hemophilia A
Keywords: Phase 1, Safety, Pharmacokinetic, Pharmacodynamic
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Catalyst BiosciencesIndustry (pharma, biotech, devices)
Study start: Dec 2011
Primary completion: Oct 2015 (actual)
Study completion: Oct 2015 (actual)
First posted: 23 Sep 2011 (estimated)
Results: Posted 6 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 5
Model description: The was an ascending dose trial with one open label treatment, intervention model was sequential dose escalation.

Arm	Type	Receives
1	Experimental	Biological: PF-05280602
2	Experimental	Biological: PF-05280602
3	Experimental	Biological: PF-05280602
4	Experimental	Biological: PF-05280602
5	Experimental	Biological: PF-05280602

Who may qualify

Ages: 18 to 64 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PF-052806020.5 micrograms per kilogram of PF-05280602, IV infusion, single dose	Biological	1
PF-052806024.5 micrograms per kilogram of PF-05280602, IV infusion, single dose	Biological	2
PF-052806029.0 micrograms per kilogram of PF-05280602, IV infusion, single dose	Biological	3
PF-0528060218.0 micrograms per kilogram of PF-05280602, IV infusion, single dose	Biological	4
PF-0528060230.0 micrograms per kilogram of PF-05280602, IV infusion, single dose	Biological	5

Primary outcome

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline, Day 2, Day 3, and Day 15
Supine blood pressure (BP) was measured with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mmHg) after 5 minutes of rest. The same arm (preferably the dominant arm) was to be used throughout the study.
Change From Baseline in Body Weight
Time frame: Baseline, Day 2, Day 3, and Day 15
Change From Baseline in Body Temperature
Time frame: Baseline, Day 2, Day 3, and Day 15
Body temperature was measured by mouth (oral) or ear (tympanic). A temperature greater than 38.5 degree Celsius was considered a fever.
Change From Baseline in Respiration Rate
Time frame: Baseline, Day 2, Day 3, and Day 15
Respiration rate measured as respirations per minute (resp/min).
Change From Baseline in Supine Pulse Rate
Time frame: Baseline, Day 2, Day 3, and Day 15
Change from baseline is the vital sign value at Day 2, Day 3, and Day 15 minus vital sign value at baseline.
Number of Participants With Changes Since Previous Physical Examination
Time frame: Baseline (Day 0), Day 1, Day 2, Day 3, Day 15
Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner. A complete physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, genitourinary, gastrointestinal, musculoskeletal, and neurological systems. The limited or abbreviated physical examination focused on general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Time frame: Baseline through Day 15
ECG findings of potential clinical concern were: PR interval greater than or equal to (>=)300 milliseconds (msec), >=25% increase from baseline for baseline values >200 msec, >=50% increase from baseline for baseline values less than or equal to (<=)200 msec; QRS complex >=140 msec or >=50% increase from baseline; QTcF interval (Fridericia's correction) >=450 msec or >=30 msec increase from baseline.
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs (Except Hemophilia AEs)
Time frame: Baseline through Day 60
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 15 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Number of Participants With Treatment-Emergent Hemophilia AEs and Withdrawals Due to Hemophilia AEs
Time frame: Baseline through Day 60
Hemophilia AEs included spontaneous (no known contributing factor) and traumatic (known or presumed contributing factor/reason) bleeding episodes.
Number of Treatment-Emergent AEs and SAEs by Severity (Except Hemophilia AEs)
Time frame: Baseline through Day 60
AE severity were graded as mild, moderate, or severe. Mild severity AEs do not interfere with the participant's usual function. Moderate AEs interfere to some extent with the participant's usual function. Severe AEs interfere significantly with the participant's usual function.
Number of Treatment-Emergent Hemophilia AEs by Severity
Time frame: Baseline through Day 60
Mild severity AEs do not interfere with the participant's usual function. Moderate AEs interfere to some extent with the participant's usual function. Severe AEs interfere significantly with the participant's usual function.
Number of Participants With Treatment-Emergent Abnormal Troponin-T Levels by Magnitude
Time frame: Baseline through Day 15
Troponin-T is a cardiac marker for the evaluation of possible cardiovascular injury. Troponin-T levels of potential clinical concern are values >1.5 times the upper limit of normal (1.5X ULN) or >=2.5X ULN.
Number of Participants With Treatment-Emergent Abnormal Anti-Thrombin III (ATIII) Levels by Magnitude
Time frame: Baseline through Day 3
ATIII is a protein in the blood that blocks abnormal blood clots from forming. Low levels of ATIII can cause abnormal blood clots. ATIII levels of potential clinical concern are values <1X LLN and >1X ULN.
Number of Participants With Treatment-Emergent Abnormal Tissue Factor Pathway Inhibitor (TFPI) Levels by Magnitude
Time frame: Baseline through Day 3
TFPI is a polypeptide that can regulate blood coagulation. TFPI levels of potential clinical concern are values <1X LLN and >1X ULN.
Number of Participants With Treatment-Emergent Laboratory Test Abnormalities (Normal Baseline)
Time frame: Baseline through Day 15
The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, creatinine, blood urea nitrogen [BUN], glucose, uric acid, sodium, potassium, chloride, bicarbonate, calcium, albumin, total protein, creatine kinase); urinalysis (urine white blood cell [WBC], urine RBC); other (troponin T).
Number of Participants With Clinically Significant Laboratory Abnormalities Meeting Stopping Criteria
Time frame: Baseline through Day 15
Clinically significant findings for stopping rules are: hemoglobin <8 grams/deciliter (g/dL) or >20% decrease from normal baseline; WBC >20,000 cells/mm^3 or <1,500 decrease with normal baseline; platelets <100,000/mm^3 or >33% decrease from baseline; total bilirubin >1.5X ULN; AST or ALT >2.5X ULN; alkaline phosphatase >3X ULN; creatinine >1.5X baseline; BUN >31.0 mg/dL; glucose <0.6 or >1.5X reference range; uric acid > ULN; sodium >150 or <130 mEq/L; potassium >5.5 or <3.0 mEq/L; calcium >11.5 or <8.0 mg/dL; albumin <2.0 g/L; total protein <5.0 g/L; positive D-dimer at Day 15; PT prolonged by 3 seconds above baseline; ATIII < LLN and >20% decrease from baseline; troponin-T values above the reference range; fibrinogen <0.75X LLN or >25% decrease from baseline.
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)
Time frame: Baseline through Day 60
Assays for the determination of a positive immune response was performed. An antibody immune response was defined as a confirmed post-treatment positive ELISA result in combination with a negative baseline sample ELISA result. Positive antibody immune responses to PF-05280602 by ELISA was evaluated for cross reactivity to NovoSeven RT and to Factor VII.

17 secondary outcomes

Maximum Observed Plasma Concentration (Cmax)
Time frame: 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)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time frame: 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)
Terminal Elimination Half-Life (t1/2)
Time frame: 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)
Incremental Recovery (IncRec)
Time frame: 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)
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
Time frame: 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)
Mean Residence Time (MRT)
Time frame: 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)
Volume of Distribution at Steady State (Vss)
Time frame: 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)
Clearance (CL)
Time frame: 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)
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 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)
Maximum Mean Decrease From Baseline in Prothrombin Time (PT)
Time frame: Baseline through Day 15
Maximum Mean Decrease From Baseline in Activated Partial Thromboplastin Time (aPTT)
Time frame: Baseline through Day 15
Maximum Mean Increase From Baseline in Thrombin Anti-Thrombin (TAT) Complexes
Time frame: Baseline through Day 3
Maximum Mean Increase From Baseline in Prothrombin Fragments 1+2
Time frame: Baseline through Day 3
Maximum Mean Increase From Baseline in D-Dimers
Time frame: Baseline through Day 15
Maximum Mean Increase From Baseline in Endogenous Thrombin Potential (ETP)
Time frame: Baseline through Day 3
Maximum Mean Decrease From Baseline in Thrombin Generation Lag Time
Time frame: Baseline through Day 3
Maximum Mean Increase From Baseline in Peak Thrombin Generation
Time frame: Baseline through Day 3

Results and safety

Results posted to the registry on 6 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PF-05280602 0.5 mcg/kg	1	1
PF-05280602 4.5 mcg/kg	7	6
PF-05280602 9.0 mcg/kg	8	6
PF-05280602 18.0 mcg/kg	6	6
PF-05280602 30.0 mcg/kg	7	6

Primary outcome: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Time frame: Baseline, Day 2, Day 3, and Day 15. Mean (Standard Deviation). Unit: mmHg

Measure	PF-05280602 0.5 mcg/kg n = 1	PF-05280602 4.5 mcg/kg n = 6	PF-05280602 9.0 mcg/kg n = 6	PF-05280602 18.0 mcg/kg n = 6	PF-05280602 30.0 mcg/kg n = 6
SBP: Baseline	122.0 (NA)	130.2 (7.14)	120.2 (25.41)	124.2 (7.68)	125.5 (8.53)
SBP: Change at Day 2	0.0 (NA)	-8.7 (8.24)	-0.2 (14.41)	-3.0 (6.51)	-1.5 (5.58)
SBP: Change at Day 3	5.0 (NA)	-7.0 (6.99)	2.2 (19.30)	-5.5 (7.66)	0.0 (8.58)
SBP: Change at Day 15	-10.0 (NA)	-5.5 (12.18)	4.7 (18.00)	-4.5 (14.92)	1.8 (11.84)
DBP: Baseline	78.0 (NA)	73.7 (6.35)	70.5 (10.97)	75.8 (4.67)	77.0 (6.87)
DBP: Change at Day 2	2.0 (NA)	-2.8 (6.43)	2.7 (6.28)	-0.8 (5.12)	-3.3 (5.50)
DBP: Change at Day 3	-3.0 (NA)	-6.5 (6.57)	3.3 (6.56)	-2.2 (8.11)	4.3 (10.41)
DBP: Change at Day 15	-9.0 (NA)	-3.5 (11.41)	6.0 (13.11)	-4.3 (11.15)	-4.5 (5.65)

Population analysed: The safety population included all enrolled participants who received the study drug.

Primary outcome: Change From Baseline in Body Weight

Time frame: Baseline, Day 2, Day 3, and Day 15. Mean (Standard Deviation). Unit: kilograms (kg)

Measure	PF-05280602 0.5 mcg/kg n = 1	PF-05280602 4.5 mcg/kg n = 6	PF-05280602 9.0 mcg/kg n = 6	PF-05280602 18.0 mcg/kg n = 6	PF-05280602 30.0 mcg/kg n = 6
Baseline	72.7 (NA)	75.0 (12.65)	78.7 (10.73)	78.0 (11.31)	73.4 (6.88)
Change at Day 2	-0.9 (NA)	-1.0 (0.98)	-0.6 (0.72)	-0.8 (1.31)	-0.4 (0.83)
Change at Day 3	-0.8 (NA)	-0.6 (0.85)	-0.5 (0.60)	-0.8 (1.39)	-0.3 (0.56)
Change at Day 15	-0.5 (NA)	0.4 (1.09)	0.6 (1.55)	0.6 (1.26)	0.2 (0.59)

Population analysed: The safety population included all enrolled participants who received the study drug.

Primary outcome: Change From Baseline in Body Temperature

Time frame: Baseline, Day 2, Day 3, and Day 15. Mean (Standard Deviation). Unit: degree Celcius

Measure	PF-05280602 0.5 mcg/kg n = 1	PF-05280602 4.5 mcg/kg n = 6	PF-05280602 9.0 mcg/kg n = 6	PF-05280602 18.0 mcg/kg n = 6	PF-05280602 30.0 mcg/kg n = 6
Baseline	36.1 (NA)	36.5 (0.29)	36.5 (0.34)	36.6 (0.30)	36.4 (0.43)
Change at Day 2	0.4 (NA)	-0.4 (0.62)	-0.1 (0.30)	0.1 (0.34)	0.2 (0.29)
Change at Day 3	0.3 (NA)	-0.2 (0.60)	0.1 (0.15)	-0.0 (0.41)	0.2 (0.13)
Change at Day 15	0.3 (NA)	0.1 (0.39)	0.1 (0.36)	0.1 (0.24)	0.2 (0.60)

Population analysed: The safety population included all enrolled participants who received the study drug.

Primary outcome: Change From Baseline in Respiration Rate

Time frame: Baseline, Day 2, Day 3, and Day 15. Mean (Standard Deviation). Unit: resp/min

Measure	PF-05280602 0.5 mcg/kg n = 1	PF-05280602 4.5 mcg/kg n = 6	PF-05280602 9.0 mcg/kg n = 6	PF-05280602 18.0 mcg/kg n = 6	PF-05280602 30.0 mcg/kg n = 6
Baseline	12.0 (NA)	15.0 (2.76)	15.2 (2.04)	15.7 (1.97)	16.0 (2.83)
Change at Day 2	0.0 (NA)	0.5 (1.76)	0.3 (3.50)	2.2 (2.56)	0.5 (1.22)
Change at Day 3	0.0 (NA)	0.2 (3.37)	0.3 (3.50)	1.7 (1.63)	0.2 (2.23)
Change at Day 15	2.0 (NA)	0.7 (4.32)	-0.2 (2.14)	1.2 (3.49)	-0.3 (1.97)

Population analysed: The safety population included all enrolled participants who received the study drug.

17 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to 28 days after last study drug administration (Day 60). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PF-05280602 0.5 mcg/kg	0 of 1 (0%)	1 of 1 (100%)	Not reported
PF-05280602 4.5 mcg/kg	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
PF-05280602 9.0 mcg/kg	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
PF-05280602 18.0 mcg/kg	0 of 6 (0%)	3 of 6 (50%)	Not reported
PF-05280602 30.0 mcg/kg	0 of 6 (0%)	3 of 6 (50%)	Not reported

Limitations and caveats (from the sponsor): The protocol was amended to a starting dose of 4.5 mcg/kg. The positive anti-PF-05280602 antibody was cross-reactive with NovoSeven and native Factor VII and the weak positive immune response at Day 60 may represent a false-positive test result.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

23 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-05280602 in people with Hemophilia A, run by Catalyst Biosciences at 23 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Italy, United Kingdom, Belgium, Hungary and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) (time frame: Baseline, Day 2, Day 3, and Day 15). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01439971.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2017.