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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01439971
First Posted: September 23, 2011
Last Update Posted: May 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Catalyst Biosciences
Results First Submitted: October 20, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition: Hemophilia A
Intervention: Biological: PF-05280602

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This was an open-label study to characterize the single dose pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of 5 intravenous dose levels of PF-05280602 (0.5, 4.5, 9.0, 18.0 and 30.0 micrograms/kilogram [mcg/kg]).

Reporting Groups
  Description
PF-05280602 0.5 mcg/kg PF-05280602 0.5 mcg/kg, the original lowest dosing arm, was administered as a single dose of bolus intravenous infusion on Day 1. The protocol was amended after a single participant was enrolled and the starting dose was changed to 4.5 mcg/kg.
PF-05280602 4.5 mcg/kg PF-05280602 4.5 mcg/kg was administered as a single dose of bolus intravenous infusion on Day 1.
PF-05280602 9.0 mcg/kg PF-05280602 9.0 mcg/kg was administered as a single dose of bolus intravenous infusion on Day 1.
PF-05280602 18.0 mcg/kg PF-05280602 18.0 mcg/kg was administered as a single dose of bolus intravenous infusion on Day 1.
PF-05280602 30.0 mcg/kg PF-05280602 30.0 mcg/kg was administered as a single dose of bolus intravenous infusion on Day 1.

Participant Flow:   Overall Study
    PF-05280602 0.5 mcg/kg   PF-05280602 4.5 mcg/kg   PF-05280602 9.0 mcg/kg   PF-05280602 18.0 mcg/kg   PF-05280602 30.0 mcg/kg
STARTED   1   7   8   6   7 
Received Treatment   1   6   6   6   6 
COMPLETED   1   6   6   6   6 
NOT COMPLETED   0   1   2   0   1 
Required number in cohort dosed                0                1                2                0                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The baseline analysis population included all enrolled participants who received the study drug.

Reporting Groups
  Description
PF-05280602 0.5 mcg/kg PF-05280602 0.5 mcg/kg, the original lowest dosing arm, was administered as a single dose of bolus intravenous infusion on Day 1. The protocol was amended after a single participant was enrolled and the starting dose was changed to 4.5 mcg/kg.
PF-05280602 4.5 mcg/kg PF-05280602 4.5 mcg/kg was administered as a single dose of bolus intravenous infusion on Day 1.
PF-05280602 9.0 mcg/kg PF-05280602 9.0 mcg/kg was administered as a single dose of bolus intravenous infusion on Day 1.
PF-05280602 18.0 mcg/kg PF-05280602 18.0 mcg/kg was administered as a single dose of bolus intravenous infusion on Day 1.
PF-05280602 30.0 mcg/kg PF-05280602 30.0 mcg/kg was administered as a single dose of bolus intravenous infusion on Day 1.
Total Total of all reporting groups

Baseline Measures
   PF-05280602 0.5 mcg/kg   PF-05280602 4.5 mcg/kg   PF-05280602 9.0 mcg/kg   PF-05280602 18.0 mcg/kg   PF-05280602 30.0 mcg/kg   Total 
Overall Participants Analyzed 
[Units: Participants]
 1   6   6   6   6   25 
Age [1] 
[Units: Years]
Mean (Standard Deviation)
 59.0 [1]   32.7  (13.4)   38.5  (12.1)   32.8  (12.3)   41.0  (15.7)   37.2  (13.6) 
[1] Single participant in cohort
Sex: Female, Male 
[Units: Participants]
Count of Participants
           
FEMALE      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
MALE      1 100.0%      6 100.0%      6 100.0%      6 100.0%      6 100.0%      25 100.0% 


  Outcome Measures
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1.  Primary:   Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)   [ Time Frame: Baseline, Day 2, Day 3, and Day 15 ]

2.  Primary:   Change From Baseline in Body Weight   [ Time Frame: Baseline, Day 2, Day 3, and Day 15 ]

3.  Primary:   Change From Baseline in Body Temperature   [ Time Frame: Baseline, Day 2, Day 3, and Day 15 ]

4.  Primary:   Change From Baseline in Respiration Rate   [ Time Frame: Baseline, Day 2, Day 3, and Day 15 ]

5.  Primary:   Change From Baseline in Supine Pulse Rate   [ Time Frame: Baseline, Day 2, Day 3, and Day 15 ]

6.  Primary:   Number of Participants With Changes Since Previous Physical Examination   [ Time Frame: Baseline (Day 0), Day 1, Day 2, Day 3, Day 15 ]

7.  Primary:   Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings   [ Time Frame: Baseline through Day 15 ]

8.  Primary:   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 ]

9.  Primary:   Number of Participants With Treatment-Emergent Hemophilia AEs and Withdrawals Due to Hemophilia AEs   [ Time Frame: Baseline through Day 60 ]

10.  Primary:   Number of Treatment-Emergent AEs and SAEs by Severity (Except Hemophilia AEs)   [ Time Frame: Baseline through Day 60 ]

11.  Primary:   Number of Treatment-Emergent Hemophilia AEs by Severity   [ Time Frame: Baseline through Day 60 ]

12.  Primary:   Number of Participants With Treatment-Emergent Abnormal Troponin-T Levels by Magnitude   [ Time Frame: Baseline through Day 15 ]

13.  Primary:   Number of Participants With Treatment-Emergent Abnormal Anti-Thrombin III (ATIII) Levels by Magnitude   [ Time Frame: Baseline through Day 3 ]

14.  Primary:   Number of Participants With Treatment-Emergent Abnormal Tissue Factor Pathway Inhibitor (TFPI) Levels by Magnitude   [ Time Frame: Baseline through Day 3 ]

15.  Primary:   Number of Participants With Treatment-Emergent Laboratory Test Abnormalities (Normal Baseline)   [ Time Frame: Baseline through Day 15 ]

16.  Primary:   Number of Participants With Clinically Significant Laboratory Abnormalities Meeting Stopping Criteria   [ Time Frame: Baseline through Day 15 ]

17.  Primary:   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 ]

18.  Secondary:   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) ]

19.  Secondary:   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) ]

20.  Secondary:   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) ]

21.  Secondary:   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) ]

22.  Secondary:   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) ]

23.  Secondary:   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) ]

24.  Secondary:   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) ]

25.  Secondary:   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) ]

26.  Secondary:   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) ]

27.  Secondary:   Maximum Mean Decrease From Baseline in Prothrombin Time (PT)   [ Time Frame: Baseline through Day 15 ]

28.  Secondary:   Maximum Mean Decrease From Baseline in Activated Partial Thromboplastin Time (aPTT)   [ Time Frame: Baseline through Day 15 ]

29.  Secondary:   Maximum Mean Increase From Baseline in Thrombin Anti-Thrombin (TAT) Complexes   [ Time Frame: Baseline through Day 3 ]

30.  Secondary:   Maximum Mean Increase From Baseline in Prothrombin Fragments 1+2   [ Time Frame: Baseline through Day 3 ]

31.  Secondary:   Maximum Mean Increase From Baseline in D-Dimers   [ Time Frame: Baseline through Day 15 ]

32.  Secondary:   Maximum Mean Increase From Baseline in Endogenous Thrombin Potential (ETP)   [ Time Frame: Baseline through Day 3 ]

33.  Secondary:   Maximum Mean Decrease From Baseline in Thrombin Generation Lag Time   [ Time Frame: Baseline through Day 3 ]

34.  Secondary:   Maximum Mean Increase From Baseline in Peak Thrombin Generation   [ Time Frame: Baseline through Day 3 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Catalyst Biosciences
phone: 1-650-266-8671
e-mail: hlevy@catbio.com



Responsible Party: Catalyst Biosciences
ClinicalTrials.gov Identifier: NCT01439971     History of Changes
Other Study ID Numbers: B3051001
2011-002170-23 ( EudraCT Number )
First Submitted: August 26, 2011
First Posted: September 23, 2011
Results First Submitted: October 20, 2016
Results First Posted: April 6, 2017
Last Update Posted: May 12, 2017