Phase 1 N=29 Basic Science

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

Hemophilia A

Bottom Line

View on ClinicalTrials.gov: NCT01439971 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Apr 2017

Primary outcome: Primary: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) — 122.0; 130.2; 120.2; 124.2 mmHg

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: PF-05280602 (Biological)
Age: Adult · 18+ yrs
Sex: Male
Sponsor: Catalyst Biosciences
Primary completion: Oct 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	122.0; 130.2; 120.2; 124.2; 125.5; 0.0	—
PRIMARY Change From Baseline in Body Weight	72.7; 75.0; 78.7; 78.0; 73.4; -0.9	—
PRIMARY Change From Baseline in Body Temperature	36.1; 36.5; 36.5; 36.6; 36.4; 0.4	—
PRIMARY Change From Baseline in Respiration Rate	12.0; 15.0; 15.2; 15.7; 16.0; 0.0	—
PRIMARY Change From Baseline in Supine Pulse Rate	62.0; 64.8; 69.3; 60.7; 66.5; 1.0	—
PRIMARY Number of Participants With Changes Since Previous Physical Examination	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs (Except Hemophilia AEs)	1; 4; 4; 3; 2; 0	—
PRIMARY Number of Participants With Treatment-Emergent Hemophilia AEs and Withdrawals Due to Hemophilia AEs	1; 1; 1; 1; 2; 0	—
PRIMARY Number of Treatment-Emergent AEs and SAEs by Severity (Except Hemophilia AEs)	2; 6; 5; 7; 1; 1	—
PRIMARY Number of Treatment-Emergent Hemophilia AEs by Severity	1; 0; 0; 0; 0; 1	—
PRIMARY Number of Participants With Treatment-Emergent Abnormal Troponin-T Levels by Magnitude	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Treatment-Emergent Abnormal Anti-Thrombin III (ATIII) Levels by Magnitude	0; 0; 0; 0; 2; 0	—
PRIMARY Number of Participants With Treatment-Emergent Abnormal Tissue Factor Pathway Inhibitor (TFPI) Levels by Magnitude	0; 1; 2; 0; 0; 1	—
PRIMARY Number of Participants With Treatment-Emergent Laboratory Test Abnormalities (Normal Baseline)	0; 0; 2; 1; 2	—
PRIMARY Number of Participants With Clinically Significant Laboratory Abnormalities Meeting Stopping Criteria	0; 0; 0; 0; 0; 0	—
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)	0; 0; 0; 1; 0; 0	—
SECONDARY Maximum Observed Plasma Concentration (Cmax)	1.68; 84.78; 183.1; 496.2; 814.8	—
SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	3.82; 300.7; 638.9; 1557; 2788	—
SECONDARY Terminal Elimination Half-Life (t1/2)	NA; 3.533; 3.637; 3.303; 3.580	—
SECONDARY Incremental Recovery (IncRec)	3.48; 18.49; 20.06; 27.67; 26.87	—
SECONDARY Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)	NA; 300.7; 638.9; 1557; 2788	—
SECONDARY Mean Residence Time (MRT)	NA; 7.948; 5.697; 4.963; 5.087	—
SECONDARY Volume of Distribution at Steady State (Vss)	NA; 0.1168; 0.08060; 0.05651; 0.05494	—
SECONDARY Clearance (CL)	NA; 0.01502; 0.01423; 0.01149; 0.01089	—
SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax)	0.167; 0.167; 0.242; 0.142; 0.150	—
SECONDARY Maximum Mean Decrease From Baseline in Prothrombin Time (PT)	-0.70; -3.37; -3.80; -3.85; -4.45	—
SECONDARY Maximum Mean Decrease From Baseline in Activated Partial Thromboplastin Time (aPTT)	-1.30; -17.93; -24.47; -43.02; -46.85	—
SECONDARY Maximum Mean Increase From Baseline in Thrombin Anti-Thrombin (TAT) Complexes	3.70; 23.82; 4.72; 5.52; 22.47	—
SECONDARY Maximum Mean Increase From Baseline in Prothrombin Fragments 1+2	38.0; 31.8; 66.4; 76.7; 238.3	—
SECONDARY Maximum Mean Increase From Baseline in D-Dimers	240.0; 75.0; 28.3; 88.3; 238.3	—
SECONDARY Maximum Mean Increase From Baseline in Endogenous Thrombin Potential (ETP)	13.400; 212.643; 186.196; 287.173; 522.758	—
SECONDARY Maximum Mean Decrease From Baseline in Thrombin Generation Lag Time	-0.540; -6.235; -7.088; -13.400; -2.425	—
SECONDARY Maximum Mean Increase From Baseline in Peak Thrombin Generation	-0.620; 17.982; 16.568; 23.362; 49.130	—

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01439971). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.