Phase 1 N=6 Basic Science

Study to Evaluate Safety and Tolerability of a Single Dose of PF-06741086 in Chinese Adult Participants With Severe Hemophilia

Severe Hemophilia

Bottom Line

View on ClinicalTrials.gov: NCT04878731 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jul 2023

Primary outcome: Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) — 1; 0; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: PF-06741086 (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: Male
Sponsor: Pfizer
Primary completion: Aug 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	1; 0; 0	—
PRIMARY Number of Participants With Serious Adverse Events (SAEs)	—	—
PRIMARY Number of Participants With Maximum Grade 3 or 4 or 5 TEAEs	—	—
PRIMARY Number of Participants With TEAEs Leading to Permanent or Temporary Discontinuation From Study	—	—
PRIMARY Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality	6; 1; 2	—
PRIMARY Mean Absolute Value of Prothrombin Time (PT) / International Normalized Ratio (INR)	1.000; 0.990; 0.972; 0.960; 0.982; 0.988	—
PRIMARY Change From Baseline in PT/INR at Days 2, 7, 14, 21 and 28	-0.010; -0.028; -0.040; -0.018; -0.012	—
PRIMARY Mean Absolute Value of Activated Partial Thromboplastin Time (APTT)	85.38; 87.15; 87.78; 80.95; 64.10; 68.92	—
PRIMARY Change From Baseline in APTT at Days 2, 7, 14, 21 and 28	1.77; 2.40; -4.43; -21.28; -16.47	—
PRIMARY Mean Absolute Value of Fibrinogen	284.3; 267.0; 249.5; 284.0; 267.7; 273.2	—
PRIMARY Change From Baseline in Fibrinogen at Days 2, 7, 14, 21 and 28	-17.3; -34.8; -0.3; -16.7; -11.2	—
PRIMARY Mean Absolute Value of Antithrombin III (ATIII)	92.75; 88.68; 94.07; 97.98; 96.10; 97.18	—
PRIMARY Change From Baseline in ATIII at Days 2, 7, 14, 21 and 28	-4.07; 1.32; 5.23; 3.35; 4.43	—
PRIMARY Mean Absolute Value of Cardiac Troponin I (cTnI)	0.0250; 0.0250; 0.0250	—
PRIMARY Change From Baseline in cTnI at Days 2 and 4	0.0000; 0.0000	—
PRIMARY Number of Participants With Vital Signs Data Meeting Categorical Criteria of Potential Clinical Concern	0; 0; 0; 0; 1; 0	—
PRIMARY Change From Baseline in Supine Systolic BP at Days 1, 2, 3, 4, 7, 14, 21 and 28	2.50; 1.67; 4.17; -1.83; 3.00; -0.67	—
PRIMARY Change From Baseline in Diastolic Systolic BP at Days 1, 2, 3, 4, 7, 14, 21 and 28	-2.67; -3.83; -6.33; -8.67; -3.50; -5.17	—
PRIMARY Change From Baseline in Supine Pulse Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28	-1.33; -2.00; 0.33; -1.50; -5.33; -6.67	—
PRIMARY Change From Baseline in Oral Temperature at Days 1, 2, 3, 4, 7, 14, 21 and 28	0.10; 0.28; 0.50; 0.17; 0.22; 0.25	—
PRIMARY Change From Baseline in Respiratory Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28	-0.50; -0.67; 0.17; -0.50; -1.50; -1.33	—
PRIMARY Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria of Potential Clinical Concern	0; 0; 0; 0; 0; 0	—
PRIMARY Change From Baseline in ECG Mean Heart Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28	0.43; -1.57; 1.43; -1.73; -1.57; -3.07	—
PRIMARY Change From Baseline in PR Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28	-4.22; 0.45; -8.38; -6.55; -10.88; -2.72	—
PRIMARY Change From Baseline in QRS Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28	-2.27; -4.27; -2.27; -1.60; 1.57; -2.77	—
PRIMARY Change From Baseline in QT Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28	-6.57; -0.90; -11.07; -0.07; 2.60; 0.77	—
PRIMARY Change From Baseline in QT Interval Corrected at Days 1, 2, 3, 4, 7, 14, 21 and 28	-4.15; -4.82; -7.15; -4.15; -0.32; -7.82	—
PRIMARY Change From Baseline in Corrected QT Interval (Fridericia Method) (QTcF Interval) at Days 1, 2, 3, 4, 7, 14, 21 and 28	-5.38; -3.22; -8.55; -2.88; 0.28; -4.88	—
PRIMARY Number of Participants With Physical Examination Findings	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Injection Site Reactions	—	—
SECONDARY Mean Plasma Marstacimab Concentration Versus Time at Days 1, 2, 3, 4, 7, 14, 21 and 28	0.0000; 582.0; 1746; 5647; 9033; 14300	—
SECONDARY Maximum Plasma Concentration (Cmax) of Marstacimab	15610	—
SECONDARY Time for Cmax (Tmax) of Marstacimab	73.15	—
SECONDARY Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Marstacimab	2917000	—
SECONDARY Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of Marstacimab	4549000	—
SECONDARY Terminal Half-Life (t1/2) of Marstacimab	90.48	—
SECONDARY Apparent Volume of Distribution (Vz/F) of Marstacimab	8.305	—
SECONDARY Apparent Clearance (CL/F) of Marstacimab	0.06595	—
SECONDARY Maximum Increase From Baseline for Tissue Factor Pathway Inhibitor (TFPI), Day 1 up to Day 28	79.50	—
SECONDARY Area Under the Curve (AUC) of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TFPI	5730.07; 15425.73; 15526.33	—
SECONDARY Maximum Increase From Baseline for Prothrombin Fragments 1+2 (PF 1+2), Day 1 up to Day 28	531.9	—
SECONDARY AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for PF 1+2	56871.2823; 116439.2948; 144733.7020	—
SECONDARY Maximum Increase From Baseline for D-Dimer, Day 1 up to Day 28	0.463	—
SECONDARY AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for D-Dimer	46.245; 110.855; 176.463	—
SECONDARY Maximum Decrease From Baseline for Dilute Prothrombin Time (dPT), Day 1 up to Day 28	-19.62	—
SECONDARY AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for dPT	-1910.10; -4079.87; -6792.18	—
SECONDARY Maximum Decrease From Baseline for Thrombin Generation Assay (TGA) Lag Time, Day 1 up to Day 28	-0.92	—
SECONDARY AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA Lag Time	-95.10; -188.08; -174.70	—
SECONDARY Maximum Increase From Baseline for TGA Peak, Day 1 up to Day 28	105.83	—
SECONDARY AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA Peak	10584.58; 20276.98; 28016.08	—
SECONDARY Maximum Increase From Baseline for TGA Endogenous Thrombin Potential (EGTP), Day 1 up to Day 28	1093.7	—
SECONDARY AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA EGTP	123700.0; 238797.8; 332461.2	—
SECONDARY Number of Participants With Anti-Drug Antibody (ADA) Against Marstacimab	0; 0; 1; 1	—
SECONDARY Number of Participants With Neutralizing Antibody (NAb) Against Marstacimab	0; 0; 0; 0	—

Summary

This Phase 1 study will be a single-arm, open-label, non-randomized, non-controlled investigation of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06741086 in Chinese adult participants with severe hemophilia.

Eligibility Criteria

Inclusion Criteria

Participant must be male and 18 to 450 msec for male participants or QTc >480 msec in participants with bundle branch block.
Individuals with hypersensitivity or an allergic reaction to hamster protein or other components of the study intervention.
A positive urine drug screen
Current routine prophylaxis with bypassing agent or non coagulation factor-replacement therapy (eg, emicizumab)
Regular, concomitant therapy with immunomodulatory drugs
Ongoing or planned use of immune tolerance induction or prophylaxis with FVIII or FIX replacement during the study.
Participation in other studies involving investigational drug(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry and/or during study participation.
CD4 cell count ≤200/uL if human immunodeficiency virus (HIV)-positive
Baseline ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04878731). 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.