Phase 2
N=26
PF-06741086 Multiple Dose Study in Severe Hemophilia
Hemophilia A or B
Bottom Line
View on ClinicalTrials.gov: NCT02974855 ↗Enrolled (actual)
26
Serious AEs
15.2%
Results posted
Dec 2019
Primary outcome: Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) — 7; 4; 6; 4 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- PF-06741086 (Biological)
- Age
- Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Pfizer
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
7; 4; 6; 4; 11; 21 | — |
| PRIMARY Number of Participants Discontinued From Study Due to TEAEs |
0; 1; 0; 1; 1; 2 | — |
| PRIMARY Number of Participants With Abnormal Laboratory Findings-Hematology |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Laboratory Findings-Clinical Chemistry |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Laboratory Findings-Urinalysis |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Change From Baseline for Globulin by Dose Cohort |
-0.3; -1.7; -1.3; 0.4; 0.1; -0.7 | — |
| PRIMARY Change From Baseline for Prothrombin International Normalized Ratio (PT/INR) by Dose Cohort |
-0.03; -0.02; 0.05; 0.03; 0.00; 0.01 | — |
| PRIMARY Change From Baseline for Activated Partial Thromboplastin Time (aPTT) by Dose Cohort |
8.49; 10.63; 11.03; -12.26; -1.89; 3.98 | — |
| PRIMARY Change From Baseline for Fibrinogen by Dose Cohort |
-49.7; -59.7; -3.5; -54.4; -52.1; -42.6 | — |
| PRIMARY Change From Baseline for Antithrombin III by Dose Cohort |
2.1; -1.8; 3.7; -7.3; -2.6; -1.0 | — |
| PRIMARY Change From Baseline for Troponin I by Dose Cohort |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Vital Signs Data Meeting Pre-specified Criteria |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Electrocardiogram (ECG) Change Meeting Pre-specified Criteria |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Changes in Physical Examination Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Infusion and Injection Site Reactions |
3; 1; 0; 1; 4; 5 | — |
| SECONDARY Annualized Bleeding Rate (ABR) |
23.00; 14.67; 20.33; 17.33; 20.17; 18.83 | 0.0002 sig |
| SECONDARY Plasma PF-06741086 Concentrations |
12180; 15620; 11640; 18130; 15150; 17560 | — |
| SECONDARY Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06741086 |
1818000; 2675000; 2806000; 2495000; 2130000 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of PF-06741086 |
14880; 19480; 23070; 19680; 17110; 61850 | — |
| SECONDARY Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06741086 |
7980; 13040; 15660; 11140; 9429; 42120 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of PF-06741086 |
70.0; 69.7; 71.6; 70.7; 70.1; 23.7 | — |
| SECONDARY Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of PF-06741086 |
9045000; 3309000; 11090000; 9248000; 9146000 | — |
| SECONDARY Apparent Clearance After Oral Dose (CL/F) of PF-06741086 |
33.16; 45.34; 40.60; 32.43; 32.79 | — |
| SECONDARY Change From Baseline in Total Tissue Factor Pathway Inhibitor (TFPI) |
3.9; -13.4; 8.2; 0.4; 2.1; 39.4 | — |
| SECONDARY Change From Baseline in Thrombin Generation (TGA) Lag Time |
-7.16; -2.77; -3.93; -4.13; -5.64; -6.80 | — |
| SECONDARY Change From Baseline in Thrombin Generation (TGA) Peak |
72.93; 70.92; 68.18; 63.41; 68.17; 60.00 | — |
| SECONDARY Change From Baseline in Endogenous Thrombin Generation (TGA) Potential |
864.0; 816.8; 999.8; 1065.3; 964.6; 766.7 | — |
| SECONDARY Change From Baseline in Prothrombin Fragments 1 + 2 |
430.0; 498.3; 275.7; 438.9; 434.4; 548.1 | — |
| SECONDARY Change From Baseline in D-Dimer |
0.0393; 0.0792; 0.1900; 0.1086; 0.0739; 0.2050 | — |
| SECONDARY Change From Baseline in Dilute Prothrombin Time |
-27.84; -13.32; -31.25; -17.14; -22.49; -30.03 | — |
| SECONDARY Number of Participants Who Tested Positive for Anti-PF-06741086 Antibody (ADA) |
0; 1; 2; 0; 0; 3 | — |
| SECONDARY Number of Participants Who Tested Positive for Neutralizing Antibody (NAb) |
0; 0; 0; 0; 0; 0 | — |
Summary
This study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of multiple subcutaneous and/or intravenous doses of PF-06741086 in subjects with severe hemophilia.
Eligibility Criteria
Inclusion Criteria
- Severe hemophilia A or B (Factor VIII or Factor IX activity ≤ 1%), including patients with inhibitors to Factor VIII or Factor IX
- Episodic (on-demand) treatment regimen prior to screening
- At least 6 acute bleeding episodes during the 6-month period prior to screening
Exclusion Criteria
- Known coronary artery, thrombotic, or ischemic disease
- Currently receiving treatment for acute bleeding episodes with APCC and cannot substitute treatment with rFVIIa
Data sourced from ClinicalTrials.gov (NCT02974855). 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.