Severe HemophiliaPhase 1NCT04878731

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

A Phase 1 study testing PF-06741086 in people with Severe Hemophilia, run by Pfizer at 1 site in China.

Completed

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

Trial 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. Read more about this study

Who is it for?: Ages 18 to 74 years, men only
Conditions the study is for: Severe Hemophilia
What is being tested?: PF-06741086
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 6 participants
Where: 1 siteChina
Study dates: 16 Apr 2021to 10 Aug 2021
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 74 years
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Participant must be male and 18 to <75 years of age with a minimum body weight of 30 kg at screening.
Participants with a diagnosis of severe hemophilia A or B (FVIII or FIX activity <1%, respectively)
Participants without inhibitor must also meet the following criteria:
No detectable or documented history of inhibitors
Participants with on-demand treatment regimen with ≥6 acute bleeding episodes (spontaneous or traumatic) that required coagulation factor infusion during the 4 months period prior to enrollment and willing to continue to receive on demand treatment during the study.
Participants with Inhibitor must also meet the following criteria:
Documentation of current high titer inhibitor (≥5 BU/mL) or current low titer inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement and with FVIII or FIX recovery <60% of expected within previous 4 months prior to screening.
Participants with on-demand treatment regimen with ≥6 bleeding episodes (spontaneous and/or traumatic) necessitating treatment with bypass factor for at least 4 months prior to screening and willing to continue to receive on-demand treatment during the study.

Who cannot join

Previous or current treatment for and/or history of coronary artery diseases, venous or arterial thrombosis or ischemic disease
Known planned surgical procedure during the planned study period.
Known hemostatic defect other than hemophilia A or B.
Abnormal renal or hepatic function
Current unstable liver or biliary disease
Abnormal hematologic parameters

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Abnormal coagulation activity
Other acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator.
Corrected QT interval (QTc) >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

Trial locations and contacts

1 site in 1 country.

China1 site

Institute of Hematology, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020

Other trials in China

About this study

Official title: A PHASE 1, SINGLE-ARM, OPEN-LABEL, NON-RANDOMIZED, NON-CONTROLLED MULTICENTER STUDY TO EVALUATE THE PHARMACOKINETICS, PHARMACODYNAMICS, SAFETY, AND TOLERABILITY OF A SINGLE SUBCUTANEOUS DOSE OF PF-06741086 IN CHINESE ADULT PARTICIPANTS WITH SEVERE HEMOPHILIA

Conditions: Severe Hemophilia
Being tested: PF-06741086
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-06741086Biological
single dose SC injection of 300 mg PF-06741086

Study groups in NCT04878731
Study group	Role	What they receive
single arm	Experimental	PF-06741086 300mg subcutaneous(SC) Receives: Biological: PF-06741086

What is being measured

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

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs that started during the effective duration of treatment regardless of whether a similar event existed at baseline. Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL);Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=events with life-threatening consequences, urgent intervention indicated;Grade 5= death related to AE.Treatment-related TEAEs were determined by investigator.
Measured: Day 1 to Day 42
Number of Participants With Serious Adverse Events (SAEs)
An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.
Measured: Day 1 to Day 42
Number of Participants With Maximum Grade 3 or 4 or 5 TEAEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs that started during the effective duration of treatment regardless of whether a similar event existed in the baseline period. Grades of AEs were defined by NCI CTCAE version 5.0. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-related TEAEs were determined by the investigator.
Measured: Day 1 to Day 42
Number of Participants With TEAEs Leading to Permanent or Temporary Discontinuation From Study
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs that started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period. Grades of AEs were defined by NCI CTCAE version 5.0. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-related TEAEs were determined by the investigator.
Measured: Day 1 to Day 42
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Laboratory assessments included chemistry, hematology, Prothrombin Time/International Normalized Ratio (PT/INR), Activated Partial Thromboplastin Time (APTT), urinalysis, fibrinogen, Antithrombin III (ATIII) activity, and Cardiac Troponin I (cTnI). Laboratory test abnormalities reported by at least 1 participant are reported in this outcome measure. ULN = upper limit of normal.
Measured: Day 1 to Day 28
Mean Absolute Value of Prothrombin Time (PT) / International Normalized Ratio (INR)
PT is one of the laboratory tests to evaluate the ability of blood clotting. The INR is derived from PT which is calculated as a ratio of a participant's PT to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the following formula: INR = Participant PT / Control PT. Blood samples were obtained to evaluate PT/INR.
Measured: Day 1, Day 2, Day 7, Day 14, Day 21, Day 28
Change From Baseline in PT/INR at Days 2, 7, 14, 21 and 28
PT is one of the laboratory tests to evaluate the ability of blood clotting. The INR is derived from PT which is calculated as a ratio of a participant's PT to a control PT standardized for the potency of the thromboplastin reagent developed by the WHO using the following formula: INR = Participant PT / Control PT. Blood samples were obtained to evaluate PT/INR.
Measured: Baseline (Day 1), Day 2, Day 7, Day 14, Day 21, Day 28
Mean Absolute Value of Activated Partial Thromboplastin Time (APTT)
The APTT is a screening test that helps evaluate a person's ability to appropriately form blood clots. It measures the number of seconds it takes for a clot to form in a sample of blood after substances (reagents) are added. Blood samples were obtained to evaluate APTT.
Measured: Day 1, Day 2, Day 7, Day 14, Day 21, Day 28
Change From Baseline in APTT at Days 2, 7, 14, 21 and 28
The APTT is a screening test that helps evaluate a person's ability to appropriately form blood clots. It measures the number of seconds it takes for a clot to form in a sample of blood after substances (reagents) are added. Blood samples were obtained to evaluate APTT.
Measured: Baseline (Day 1), Day 2, Day 7, Day 14, Day 21, Day 28
Mean Absolute Value of Fibrinogen
Fibrinogen is a protein, specifically a clotting factor (factor I), that is essential for proper blood clot formation. Blood samples were obtained to evaluate the amount of fibrinogen.
Measured: Day 1, Day 2, Day 7, Day 14, Day 21, Day 28
Change From Baseline in Fibrinogen at Days 2, 7, 14, 21 and 28
Fibrinogen is a protein, specifically a clotting factor (factor I), that is essential for proper blood clot formation. Blood samples were obtained to evaluate the amount of fibrinogen.
Measured: Baseline (Day 1), Day 2, Day 7, Day 14, Day 21, Day 28
Mean Absolute Value of Antithrombin III (ATIII)
ATIII is a nonvitamin K-dependent protease that inhibits coagulation by lysing thrombin and factor Xa. The antithrombin activity test measures how well the protein inhibits thrombin, with a reference range of 75% - 125%. Blood samples were obtained to evaluate ATIII activity.
Measured: Day 1, Day 2, Day 7, Day 14, Day 21, Day 28
Change From Baseline in ATIII at Days 2, 7, 14, 21 and 28
ATIII is a nonvitamin K-dependent protease that inhibits coagulation by lysing thrombin and factor Xa. The antithrombin activity test measures how well the protein inhibits thrombin, with a reference range of 75% - 125%. Blood samples were obtained to evaluate ATIII activity.
Measured: Baseline (Day 1), Day 2, Day 7, Day 14, Day 21, Day 28
Mean Absolute Value of Cardiac Troponin I (cTnI)
cTnI is one of the cardiac regulatory proteins that control the calcium mediated interaction between actin and myosin, and is considered a specific marker for cardiac damage. Blood samples were obtained to evaluate the amount of cTnI.
Measured: Day 1, Day 2, Day 4
Change From Baseline in cTnI at Days 2 and 4
cTnI is one of the cardiac regulatory proteins that control the calcium mediated interaction between actin and myosin, and is considered a specific marker for cardiac damage. Blood samples were obtained to evaluate the amount of cTnI.
Measured: Baseline (Day 1), Day 2, Day 4
Number of Participants With Vital Signs Data Meeting Categorical Criteria of Potential Clinical Concern
Vital signs measurements included blood pressure (BP), pulse rate, respiratory rate and oral temperature. Categorical classes for vital signs of potential clinical concern included: (1) systolic BP - minimum (min) value <90 mmHg, maximum (max) decrease/increase from baseline >=30 mmHg; (2) diastolic BP - min value <50 mmHg, max decrease/increase from baseline >=20 mmHg; (3) supine pulse rate - min <40 beat per minute (bpm) or max >120 bpm; (4) standing pulse rate - min <40 bpm or max >140 bpm; (5) oral temperature > 38.5 celsius degree (°C). BPs were measured in a supine position so standing BPs were not evaluated and not reported.
Measured: Day 1 to Day 28
Change From Baseline in Supine Systolic BP at Days 1, 2, 3, 4, 7, 14, 21 and 28
BPs were assessed in a supine position with a completely automated device. Categorical classes for supine systolic BP of potential clinical concern included min value <90 mmHg, max decrease/increase from baseline >=30 mmHg.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in Diastolic Systolic BP at Days 1, 2, 3, 4, 7, 14, 21 and 28
BPs were assessed in a supine position with a completely automated device. Categorical classes for supine diastolic BP of potential clinical concern included min value <50 mmHg, max decrease/increase from baseline >=20 mmHg.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in Supine Pulse Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28
Pulse rates were assessed in a supine position with a completely automated device. Categorical classes for supine pulse rate of potential clinical concern included min value <40 bpm or max value >120 bpm.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in Oral Temperature at Days 1, 2, 3, 4, 7, 14, 21 and 28
No eating, drinking, or smoking was allowed for 15 minutes prior to the measurement of oral temperature. The criterion for oral temperature of potential clinical concern was oral temperature > 38.5°C.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in Respiratory Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28
Respiratory rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Respiratory rate was measured in terms of "breaths per minute", and was measured by observing and counting the respirations of the participant for 30 seconds and multiplied by 2.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria of Potential Clinical Concern
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS and QT intervals. If a single time point ECG was abnormal, a triplicate ECG was required and obtained approximately 2-4 minutes apart; the average of triplicate ECG measurements collected at pre-dose Day 1 served as each participant's baseline value. Categorical classes for ECG data of potential clinical concern included: (1) QTcF - 450 millisecond (msec)≤ max value <480 msec, 480 msec ≤ max value <500 msec, max value ≥500 msec; 30 msec ≤ QTcF max increase from baseline <60 msec; max increase from baseline ≥60 msec; (2) PR interval - max value ≥300 msec, baseline value>200 and max increase from baseline ≥25%, baseline value ≤200 and max increase from baseline ≥50%; (3) QRS interval - max value ≥140 msec, increase from baseline ≥50%.
Measured: Day 1 to Day 28
Change From Baseline in ECG Mean Heart Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28
Heart rate was measured in terms of "beats per minute". Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. If a single time point ECG was abnormal, a triplicate ECG was required, which were obtained approximately 2-4 minutes apart; the average of the triplicate ECG measurements collected at pre-dose Day 1 served as each participant's baseline value.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in PR Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. Categorical classes for PR interval data of potential clinical concern included: max value ≥300 ms, baseline value>200 and max increase from baseline≥25%, baseline value ≤200 and max increase from baseline ≥50%.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in QRS Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. Categorical classes for QRS interval data of potential clinical concern included: max value ≥140 ms, increase from baseline ≥50%.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in QT Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in QT Interval Corrected at Days 1, 2, 3, 4, 7, 14, 21 and 28
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. The corrected QT interval (QTc) estimates the QT interval at a standard heart rate of 60 bpm.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Change From Baseline in Corrected QT Interval (Fridericia Method) (QTcF Interval) at Days 1, 2, 3, 4, 7, 14, 21 and 28
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. QTcF = QT interval corrected using the Fridericia method. Categorical classes for QTcF data of potential clinical concern included: 450 ms≤ max value <480 ms, 480≤ max value <500 ms, max value ≥500 ms; 30 ms ≤ QTcF max increase from baseline <60 ms; max increase from baseline ≥60 ms.
Measured: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Number of Participants With Physical Examination Findings
A complete PE included assessments of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A brief PE included assessments of the general appearance, the respiratory and cardiovascular systems, as well as participant reported symptoms. The full PE planned for Screening may have been performed on Day -1 before dosing at the discretion of the Investigator. If a full PE was done at Screening visit, a brief PE was to be conducted on Day-1. After Day -1, brief examinations based on signs and symptoms may have been performed if clinically indicated at the discretion of the Investigator to assess changes from baseline/previous visits of any ongoing symptoms.
Measured: Screening (Day -35 to Day -2), Day -1, Day 1 (for general appearance, heart, lungs), Day 7 (for general appearance, heart, lungs), Day 28 (for general appearance, heart, lungs)
Number of Participants With Injection Site Reactions
Grades of injection site reactions were defined according to NCI CTCAE version 5.0. Grade 1=Tenderness with or without associated symptoms (eg, warmth, erythema, itching); Grade 2= Pain, lipodystrophy, edema, phlebitis; Grade 3= Ulceration or necrosis, severe tissue damage, operative intervention indicated; Grade 4=Life-threatening consequences, urgent intervention indicated; Grade 5=death. Participants with any grade of injection site reaction are reported in this outcome measure.
Measured: Day 1 to Day 7

Secondary outcomes (24)

Mean Plasma Marstacimab Concentration Versus Time at Days 1, 2, 3, 4, 7, 14, 21 and 28
Mean plasma concentration of marstacimab after participants received a single SC injection of marstacimab 300 mg.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Plasma Concentration (Cmax) of Marstacimab
Maximum plasma concentration of marstacimab after participants received a single SC injection of marstacimab 300 mg.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Time for Cmax (Tmax) of Marstacimab
Time for Cmax of marstacimab after participants received a single SC injection of marstacimab 300 mg.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Marstacimab
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration of marstacimab after participants received a single SC injection of marstacimab 300 mg.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of Marstacimab
Area under the concentration time curve from time zero to infinity of marstacimab after participants received a single SC injection of marstacimab 300 mg.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Terminal Half-Life (t1/2) of Marstacimab
Terminal half life (t1/2) of marstacimab after participants received a single SC injection of marstacimab 300 mg. t1/2 is defined as the time for plasma concentration to decrease by one half.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Apparent Volume of Distribution (Vz/F) of Marstacimab
Apparent volume of distribution of marstacimab after participants received a single SC injection of marstacimab 300 mg. 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 plasma concentration of a drug. Vz/F was influenced by the fraction absorbed. Vz/F was calculated as dose/AUCinf. AUCinf = area under the concentration time curve from time zero to infinity.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Apparent Clearance (CL/F) of Marstacimab
Apparent clearance (CL/F) of marstacimab after participants received a single SC injection of marstacimab 300 mg. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as Dose/ (AUCinf*kel). AUCinf = area under the concentration time curve from time zero to infinity. kel = terminal phase rate constant calculated by a linear regression of the log linear concentration time curve.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for Tissue Factor Pathway Inhibitor (TFPI), Day 1 up to Day 28
TFPI is a protease inhibitor, which acts as an antagonist of the extrinsic coagulation pathway via inhibition of tissue factor-activated coagulation factor VII (FVIIa) and activated factor X (FXa). Plasma total TFPI levels were measured to reflect target binding with marstacimab. TFPI in results represented total TFPI.
Measured: Day 1 to Day 28
Area Under the Curve (AUC) of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TFPI
A change from baseline-time profile was established based on changes from baseline in TFPI at specific time points. Area under the TFPI change from baseline-time profile from time zero (Day 1) to Day 7, from time zero to Day 14 and from time zero to Day 28 are presented in this outcome measure. TFPI represented total TFPI.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for Prothrombin Fragments 1+2 (PF 1+2), Day 1 up to Day 28
PF1+2 is an in vivo endpoint reflective of coagulation pathway activation. Maximum increase from baseline for PF 1+2 was provided.
Measured: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for PF 1+2
A change from baseline-time profile was established based on changes from baseline in PF 1+2 at specific time points. Area under the PF 1+2 change from baseline-time profile from time zero (Day 1) to Day 7, from time zero to Day 14 and from time zero to Day 28 are presented in this outcome measure.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for D-Dimer, Day 1 up to Day 28
D-dimer is an in vivo endpoint reflective of coagulation pathway activation. Maximum increase from baseline for D-Dimer is provided.
Measured: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for D-Dimer
A change from baseline-time profile was established based on changes from baseline in D-dimer at specific time points. Area under the D-dimer change from baseline-time profile from time zero (Day 1) to Day 7, from time zero to Day 14 and from time zero to Day 28 are presented in this outcome measure.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Decrease From Baseline for Dilute Prothrombin Time (dPT), Day 1 up to Day 28
The dilute prothrombin time (dPT) is an ex vivo endpoint reflective of coagulation pathway activation. Maximum decrease from baseline for dPT is provided.
Measured: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for dPT
A change from baseline-time profile was established based on changes from baseline in dPT at specific time points. Area under the dPT change from baseline-time profile from time zero (Day 1) to Day 7, from time zero to Day 14 and from time zero to Day 28 are presented in this outcome measure.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Decrease From Baseline for Thrombin Generation Assay (TGA) Lag Time, Day 1 up to Day 28
TGA lag time is an ex vivo endpoint reflective of coagulation pathway activation. Maximum decrease from baseline for TGA Lag Time is provided.
Measured: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA Lag Time
A change from baseline-time profile was established based on changes from baseline in TGA lag time at specific time points. Area under the TGA lag time change from baseline-time profile from time zero (Day 1) to Day 7, from time zero to Day 14 and from time zero to Day 28 are presented in this outcome measure.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for TGA Peak, Day 1 up to Day 28
TGA peak is an ex vivo endpoint reflective of coagulation pathway activation. Maximum increase from baseline for TGA Peak is provided.
Measured: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA Peak
A change from baseline-time profile was established based on changes from baseline in TGA peak at specific time points. Area under the TGA peak change from baseline-time profile from time zero (Day 1) to Day 7, from time zero to Day 14 and from time zero to Day 28 are presented in this outcome measure.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for TGA Endogenous Thrombin Potential (EGTP), Day 1 up to Day 28
TGA EGTP is an ex vivo endpoint reflective of coagulation pathway activation. Maximum increase from baseline for TGA Endogenous Thrombin Potential is provided.
Measured: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA EGTP
A change from baseline-time profile was established based on changes from baseline in TGA EGTP at specific time points. Area under the TGA EGTP change from baseline-time profile from time zero (Day 1) to Day 7, from time zero to Day 14 and from time zero to Day 28 are presented in this outcome measure.
Measured: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Number of Participants With Anti-Drug Antibody (ADA) Against Marstacimab
Summary of ADA incidence by visit is presented. ADA positive was defined as titer >=1.54.
Measured: Day 1 pre-dose (-2 hours to -5 min prior to dosing); Day 14; Day 21; Day 28
Number of Participants With Neutralizing Antibody (NAb) Against Marstacimab
Summary of NAb incidence by visit is presented. NAb positive was defined as titer >=1.08. ADA-positive participants (defined as titer >=1.54) were analyzed for NAb.
Measured: Day 1 pre-dose (-2 hours to -5 min prior to dosing); Day 14; Day 21; Day 28

Timeline

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

16 Apr 202110 Aug 2021

First posted7 May 2021
Study start16 Apr 2021
Primary completion10 Aug 2021
Study completion10 Aug 2021

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Severe HemophiliaStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04878731
Sponsor's protocol ID: B7841010
Status last verified: Aug 2022
First submitted: 16 Apr 2021
Last updated: 7 Jul 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

Nayak S, Suzuki A, Ravva P, Raje S. Clinical Pharmacokinetics and Pharmacodynamics of Marstacimab, an Anti-tissue Factor Pathway Inhibitor Monoclonal Antibody, in Adolescent and Adult Participants with Hemophilia. Clin Pharmacokinet. 2026 Sep 4. doi: 10.1007/s40262-026-01695-5. Online ahead of print.
PubMed 42698050

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

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
RecruitingPhase 3
Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors
Hemophilia A, Hemophilia B
Active, not recruitingPhase 4
A Study to Evaluate Overall Health, Physical Activity, and Joint Outcomes in Participants With Severe or Moderate Hemophilia A Without Factor VIII Inhibitors on Emicizumab Prophylaxis
Severe Hemophilia A, Moderate Hemophilia A
RecruitingPhase 1/2
A Study to Investigate the Safety and Effectiveness of a Coagulation Factor IX Gene Insertion Therapy (REGV131-LNP1265) in Pediatric, Adolescent and Adult Participants With Hemophilia B
Hemophilia B

All Severe Hemophilia trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1, SINGLE-ARM, OPEN-LABEL, NON-RANDOMIZED, NON-CONTROLLED MULTICENTER STUDY TO EVALUATE THE PHARMACOKINETICS, PHARMACODYNAMICS, SAFETY, AND TOLERABILITY OF A SINGLE SUBCUTANEOUS DOSE OF PF-06741086 IN CHINESE ADULT PARTICIPANTS WITH SEVERE HEMOPHILIA
ClinicalTrials.gov ID: NCT04878731
Acronym / sponsor ID: B7841010
Conditions: Severe Hemophilia
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 6 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 16 Apr 2021 (actual)
Primary completion: 10 Aug 2021 (actual)
Study completion: 10 Aug 2021 (actual)
First posted: 7 May 2021 (actual)
Results: Posted 7 Jul 2023

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
single arm	Experimental	Biological: PF-06741086PF-06741086 300mg subcutaneous(SC)

Who may qualify

Ages: 18 to 74 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Participant must be male and 18 to <75 years of age with a minimum body weight of 30 kg at screening.
Participants with a diagnosis of severe hemophilia A or B (FVIII or FIX activity <1%, respectively)
Participants without inhibitor must also meet the following criteria:
Participants with Inhibitor must also meet the following criteria:

Key exclusion criteria (18 listed)

Previous or current treatment for and/or history of coronary artery diseases, venous or arterial thrombosis or ischemic disease
Known planned surgical procedure during the planned study period.
Known hemostatic defect other than hemophilia A or B.
Abnormal renal or hepatic function
Current unstable liver or biliary disease

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-06741086single dose SC injection of 300 mg PF-06741086	Biological	single arm

Primary outcome

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Day 1 to Day 42
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs that started during the effective duration of treatment regardless of whether a similar event existed at baseline. Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL);Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=events with life-threatening consequences, urgent intervention indicated;Grade 5= death related to AE.Treatment-related TEAEs were determined by investigator.
Number of Participants With Serious Adverse Events (SAEs)
Time frame: Day 1 to Day 42
An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.
Number of Participants With Maximum Grade 3 or 4 or 5 TEAEs
Time frame: Day 1 to Day 42
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs that started during the effective duration of treatment regardless of whether a similar event existed in the baseline period. Grades of AEs were defined by NCI CTCAE version 5.0. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-related TEAEs were determined by the investigator.
Number of Participants With TEAEs Leading to Permanent or Temporary Discontinuation From Study
Time frame: Day 1 to Day 42
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs that started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period. Grades of AEs were defined by NCI CTCAE version 5.0. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-related TEAEs were determined by the investigator.
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
Time frame: Day 1 to Day 28
Laboratory assessments included chemistry, hematology, Prothrombin Time/International Normalized Ratio (PT/INR), Activated Partial Thromboplastin Time (APTT), urinalysis, fibrinogen, Antithrombin III (ATIII) activity, and Cardiac Troponin I (cTnI). Laboratory test abnormalities reported by at least 1 participant are reported in this outcome measure. ULN = upper limit of normal.
Mean Absolute Value of Prothrombin Time (PT) / International Normalized Ratio (INR)
Time frame: Day 1, Day 2, Day 7, Day 14, Day 21, Day 28
PT is one of the laboratory tests to evaluate the ability of blood clotting. The INR is derived from PT which is calculated as a ratio of a participant's PT to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the following formula: INR = Participant PT / Control PT. Blood samples were obtained to evaluate PT/INR.
Change From Baseline in PT/INR at Days 2, 7, 14, 21 and 28
Time frame: Baseline (Day 1), Day 2, Day 7, Day 14, Day 21, Day 28
PT is one of the laboratory tests to evaluate the ability of blood clotting. The INR is derived from PT which is calculated as a ratio of a participant's PT to a control PT standardized for the potency of the thromboplastin reagent developed by the WHO using the following formula: INR = Participant PT / Control PT. Blood samples were obtained to evaluate PT/INR.
Mean Absolute Value of Activated Partial Thromboplastin Time (APTT)
Time frame: Day 1, Day 2, Day 7, Day 14, Day 21, Day 28
The APTT is a screening test that helps evaluate a person's ability to appropriately form blood clots. It measures the number of seconds it takes for a clot to form in a sample of blood after substances (reagents) are added. Blood samples were obtained to evaluate APTT.
Change From Baseline in APTT at Days 2, 7, 14, 21 and 28
Time frame: Baseline (Day 1), Day 2, Day 7, Day 14, Day 21, Day 28
The APTT is a screening test that helps evaluate a person's ability to appropriately form blood clots. It measures the number of seconds it takes for a clot to form in a sample of blood after substances (reagents) are added. Blood samples were obtained to evaluate APTT.
Mean Absolute Value of Fibrinogen
Time frame: Day 1, Day 2, Day 7, Day 14, Day 21, Day 28
Fibrinogen is a protein, specifically a clotting factor (factor I), that is essential for proper blood clot formation. Blood samples were obtained to evaluate the amount of fibrinogen.
Change From Baseline in Fibrinogen at Days 2, 7, 14, 21 and 28
Time frame: Baseline (Day 1), Day 2, Day 7, Day 14, Day 21, Day 28
Fibrinogen is a protein, specifically a clotting factor (factor I), that is essential for proper blood clot formation. Blood samples were obtained to evaluate the amount of fibrinogen.
Mean Absolute Value of Antithrombin III (ATIII)
Time frame: Day 1, Day 2, Day 7, Day 14, Day 21, Day 28
ATIII is a nonvitamin K-dependent protease that inhibits coagulation by lysing thrombin and factor Xa. The antithrombin activity test measures how well the protein inhibits thrombin, with a reference range of 75% - 125%. Blood samples were obtained to evaluate ATIII activity.
Change From Baseline in ATIII at Days 2, 7, 14, 21 and 28
Time frame: Baseline (Day 1), Day 2, Day 7, Day 14, Day 21, Day 28
ATIII is a nonvitamin K-dependent protease that inhibits coagulation by lysing thrombin and factor Xa. The antithrombin activity test measures how well the protein inhibits thrombin, with a reference range of 75% - 125%. Blood samples were obtained to evaluate ATIII activity.
Mean Absolute Value of Cardiac Troponin I (cTnI)
Time frame: Day 1, Day 2, Day 4
cTnI is one of the cardiac regulatory proteins that control the calcium mediated interaction between actin and myosin, and is considered a specific marker for cardiac damage. Blood samples were obtained to evaluate the amount of cTnI.
Change From Baseline in cTnI at Days 2 and 4
Time frame: Baseline (Day 1), Day 2, Day 4
cTnI is one of the cardiac regulatory proteins that control the calcium mediated interaction between actin and myosin, and is considered a specific marker for cardiac damage. Blood samples were obtained to evaluate the amount of cTnI.
Number of Participants With Vital Signs Data Meeting Categorical Criteria of Potential Clinical Concern
Time frame: Day 1 to Day 28
Vital signs measurements included blood pressure (BP), pulse rate, respiratory rate and oral temperature. Categorical classes for vital signs of potential clinical concern included: (1) systolic BP - minimum (min) value <90 mmHg, maximum (max) decrease/increase from baseline >=30 mmHg; (2) diastolic BP - min value <50 mmHg, max decrease/increase from baseline >=20 mmHg; (3) supine pulse rate - min <40 beat per minute (bpm) or max >120 bpm; (4) standing pulse rate - min <40 bpm or max >140 bpm; (5) oral temperature > 38.5 celsius degree (°C). BPs were measured in a supine position so standing BPs were not evaluated and not reported.
Change From Baseline in Supine Systolic BP at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
BPs were assessed in a supine position with a completely automated device. Categorical classes for supine systolic BP of potential clinical concern included min value <90 mmHg, max decrease/increase from baseline >=30 mmHg.
Change From Baseline in Diastolic Systolic BP at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
BPs were assessed in a supine position with a completely automated device. Categorical classes for supine diastolic BP of potential clinical concern included min value <50 mmHg, max decrease/increase from baseline >=20 mmHg.
Change From Baseline in Supine Pulse Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Pulse rates were assessed in a supine position with a completely automated device. Categorical classes for supine pulse rate of potential clinical concern included min value <40 bpm or max value >120 bpm.
Change From Baseline in Oral Temperature at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
No eating, drinking, or smoking was allowed for 15 minutes prior to the measurement of oral temperature. The criterion for oral temperature of potential clinical concern was oral temperature > 38.5°C.
Change From Baseline in Respiratory Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Respiratory rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Respiratory rate was measured in terms of "breaths per minute", and was measured by observing and counting the respirations of the participant for 30 seconds and multiplied by 2.
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Criteria of Potential Clinical Concern
Time frame: Day 1 to Day 28
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS and QT intervals. If a single time point ECG was abnormal, a triplicate ECG was required and obtained approximately 2-4 minutes apart; the average of triplicate ECG measurements collected at pre-dose Day 1 served as each participant's baseline value. Categorical classes for ECG data of potential clinical concern included: (1) QTcF - 450 millisecond (msec)≤ max value <480 msec, 480 msec ≤ max value <500 msec, max value ≥500 msec; 30 msec ≤ QTcF max increase from baseline <60 msec; max increase from baseline ≥60 msec; (2) PR interval - max value ≥300 msec, baseline value>200 and max increase from baseline ≥25%, baseline value ≤200 and max increase from baseline ≥50%; (3) QRS interval - max value ≥140 msec, increase from baseline ≥50%.
Change From Baseline in ECG Mean Heart Rate at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Heart rate was measured in terms of "beats per minute". Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. If a single time point ECG was abnormal, a triplicate ECG was required, which were obtained approximately 2-4 minutes apart; the average of the triplicate ECG measurements collected at pre-dose Day 1 served as each participant's baseline value.
Change From Baseline in PR Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. Categorical classes for PR interval data of potential clinical concern included: max value ≥300 ms, baseline value>200 and max increase from baseline≥25%, baseline value ≤200 and max increase from baseline ≥50%.
Change From Baseline in QRS Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. Categorical classes for QRS interval data of potential clinical concern included: max value ≥140 ms, increase from baseline ≥50%.
Change From Baseline in QT Interval at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals.
Change From Baseline in QT Interval Corrected at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. The corrected QT interval (QTc) estimates the QT interval at a standard heart rate of 60 bpm.
Change From Baseline in Corrected QT Interval (Fridericia Method) (QTcF Interval) at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Day 1 pre-dose (baseline); 1 hour, 2 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing; Day 2; Day 3; Day 4; Day 7; Day 14; Day 21; Day 28.
Single 12-lead ECGs were performed for all participants in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals. QTcF = QT interval corrected using the Fridericia method. Categorical classes for QTcF data of potential clinical concern included: 450 ms≤ max value <480 ms, 480≤ max value <500 ms, max value ≥500 ms; 30 ms ≤ QTcF max increase from baseline <60 ms; max increase from baseline ≥60 ms.
Number of Participants With Physical Examination Findings
Time frame: Screening (Day -35 to Day -2), Day -1, Day 1 (for general appearance, heart, lungs), Day 7 (for general appearance, heart, lungs), Day 28 (for general appearance, heart, lungs)
A complete PE included assessments of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A brief PE included assessments of the general appearance, the respiratory and cardiovascular systems, as well as participant reported symptoms. The full PE planned for Screening may have been performed on Day -1 before dosing at the discretion of the Investigator. If a full PE was done at Screening visit, a brief PE was to be conducted on Day-1. After Day -1, brief examinations based on signs and symptoms may have been performed if clinically indicated at the discretion of the Investigator to assess changes from baseline/previous visits of any ongoing symptoms.
Number of Participants With Injection Site Reactions
Time frame: Day 1 to Day 7
Grades of injection site reactions were defined according to NCI CTCAE version 5.0. Grade 1=Tenderness with or without associated symptoms (eg, warmth, erythema, itching); Grade 2= Pain, lipodystrophy, edema, phlebitis; Grade 3= Ulceration or necrosis, severe tissue damage, operative intervention indicated; Grade 4=Life-threatening consequences, urgent intervention indicated; Grade 5=death. Participants with any grade of injection site reaction are reported in this outcome measure.

24 secondary outcomes

Mean Plasma Marstacimab Concentration Versus Time at Days 1, 2, 3, 4, 7, 14, 21 and 28
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Plasma Concentration (Cmax) of Marstacimab
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Time for Cmax (Tmax) of Marstacimab
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Marstacimab
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of Marstacimab
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Terminal Half-Life (t1/2) of Marstacimab
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Apparent Volume of Distribution (Vz/F) of Marstacimab
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Apparent Clearance (CL/F) of Marstacimab
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for Tissue Factor Pathway Inhibitor (TFPI), Day 1 up to Day 28
Time frame: Day 1 to Day 28
Area Under the Curve (AUC) of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TFPI
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for Prothrombin Fragments 1+2 (PF 1+2), Day 1 up to Day 28
Time frame: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for PF 1+2
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for D-Dimer, Day 1 up to Day 28
Time frame: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for D-Dimer
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Decrease From Baseline for Dilute Prothrombin Time (dPT), Day 1 up to Day 28
Time frame: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for dPT
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Decrease From Baseline for Thrombin Generation Assay (TGA) Lag Time, Day 1 up to Day 28
Time frame: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA Lag Time
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for TGA Peak, Day 1 up to Day 28
Time frame: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA Peak
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Maximum Increase From Baseline for TGA Endogenous Thrombin Potential (EGTP), Day 1 up to Day 28
Time frame: Day 1 to Day 28
AUC of Change From Baseline Values (Days 1-7, Days 1-14, Days 1-28) for TGA EGTP
Time frame: Pre-dose, and 1 hour, 4 hours, 12 hours, 24 hours, 48 hours, 72 hours, and approximately 144 hours, 312 hours, 480 hours and 648 hours post Day 1 dosing
Number of Participants With Anti-Drug Antibody (ADA) Against Marstacimab
Time frame: Day 1 pre-dose (-2 hours to -5 min prior to dosing); Day 14; Day 21; Day 28
Number of Participants With Neutralizing Antibody (NAb) Against Marstacimab
Time frame: Day 1 pre-dose (-2 hours to -5 min prior to dosing); Day 14; Day 21; Day 28

Results and safety

Results posted to the registry on 7 Jul 2023, 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-06741086 (Marstacimab) 300 mg Subcutaneous (SC) Single Dose	6	6

Primary outcome: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Time frame: Day 1 to Day 42. Count of participants. Unit: Participants

Measure	PF-06741086 (Marstacimab) 300 mg Subcutaneous (SC) Single Dose n = 6
All-Causality TEAEs	1
Treatment-Related TEAEs	0
All-Causality Severe TEAEs	0

Population analysed: The analysis population included all enrolled participants who received at least 1 dose of study intervention.

Primary outcome: Number of Participants With Serious Adverse Events (SAEs)

Time frame: Day 1 to Day 42. Count of participants. Unit: Participants

Measure	PF-06741086 (Marstacimab) 300 mg Subcutaneous (SC) Single Dose n = 6
Value	0

Population analysed: The analysis population included all enrolled participants who received at least 1 dose of study intervention.

Primary outcome: Number of Participants With Maximum Grade 3 or 4 or 5 TEAEs

Time frame: Day 1 to Day 42. Count of participants. Unit: Participants

Measure	PF-06741086 (Marstacimab) 300 mg Subcutaneous (SC) Single Dose n = 6
Value	0

Population analysed: The analysis population included all enrolled participants who received at least 1 dose of study intervention.

Primary outcome: Number of Participants With TEAEs Leading to Permanent or Temporary Discontinuation From Study

Time frame: Day 1 to Day 42. Count of participants. Unit: Participants

Measure	PF-06741086 (Marstacimab) 300 mg Subcutaneous (SC) Single Dose n = 6
Value	0

Population analysed: The analysis population included all enrolled participants who received at least 1 dose of study intervention.

24 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline (Day 1) to Day 42. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PF-06741086 (Marstacimab) 300 mg Subcutaneous (SC) Single Dose	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42698050Nayak S, Suzuki A, Ravva P, Raje S. Clinical Pharmacokinetics and Pharmacodynamics of Marstacimab, an Anti-tissue Factor Pathway Inhibitor Monoclonal Antibody, in Adolescent and Adult Participants with Hemophilia. Clin Pharmacokinet. 2026 Sep 4. doi: 10.1007/s40262-026-01695-5. Online ahead of print.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-06741086 in people with Severe Hemophilia, run by Pfizer at 1 site in China.

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 8 inclusion and 18 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 7 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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 7 Jul 2023). 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?

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: Day 1 to Day 42). The study lists 30 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 NCT04878731, which also lists 1 linked publication.

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 7 Jul 2023.