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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001885-27 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-06741086 (Cohort 1) | Experimental |
| |
| PF-06741086 (Cohort 2) | Experimental |
| |
| PF-06741086 (Cohort 3) | Experimental |
| |
| PF-06741086 (Cohort 4) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-06741086 | Biological | PF-06741086 subcutaneous (SC) injection |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (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 or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator. | Study Day 1 to Day 113 Visit |
| Number of Participants Discontinued From Study Due to TEAEs | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. | Study Day 1 to Day 113 Visit |
| Number of Participants With Abnormal Laboratory Findings-Hematology | Hematology evaluation included: hemoglobin, hematocrit, erythrocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils and monocytes. Predefined criteria for hemoglobin and hematocrit: <0.8*lower limit of normal (LLN) or <0.8*Baseline(Baseline <1.0*LLN); for platelets: <100,000*10^3/mm^3 or <= 0.77*Baseline (Baseline <1.0*LLN). | Baseline to Study Day 113 Visit |
| Number of Participants With Abnormal Laboratory Findings-Clinical Chemistry | Clinical chemistry evaluation included bilirubin, direct and indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, triglycerides, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase, troponin I, cholesterol and fibrinogen. |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Bleeding Rate (ABR) | Pre-treatment ABR = number of bleeding episodes within 6 months prior to study enrollment (total number of bleeding episodes in hemophilia history CRF) × 2; On-study ABR = number of bleeding episodes occurred within 9 days after the last dose / ([last dose date + 9 - first dose date + 1] / 365.25) The historical On Demand group was constructed using the following internal Pfizer studies: ReFacto AF 3082B2-4432 (B1831004), BeneFIX B1821010, and BeneFIX 3090A1-400 (B1821004). Participants who were on On Demand treatment in B1831004, as well as data from the On Demand period in B1821004 and B1821010 were used to construct the historical On Demand group. The resulting dataset were further filtered to match the key inclusion/exclusion criteria of Study B7841002 based on age and factor activity (18 <=age <=65 and factor activity <=1%). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Denver Hemophilia and Thrombosis Center - Pharmacy | Aurora | Colorado | 80045 | United States | ||
| UC Denver Hemophilia and Thrombosis Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35999026 | Derived | Mahlangu JN, Lamas JL, Morales JC, Malan DR, Salek SZ, Wang M, Boggio LN, Hegemann I, Mital A, Cardinal M, Zhu T, Sun P, Arkin S. A phase 1b/2 clinical study of marstacimab, targeting human tissue factor pathway inhibitor, in haemophilia. Br J Haematol. 2023 Jan;200(2):229-239. doi: 10.1111/bjh.18420. Epub 2022 Aug 23. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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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A total of 27 participants were enrolled in the study and assigned to 1 of 4 cohorts. Only 26 participants received the study treatment and 1 participant withdrew after randomization but prior to dosing.
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-06741086 300 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| FG001 | PF-06741086 300 mg SC Loading + 150 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg loading dose on Day 1 and 150 mg subcutaneously (SC) once weekly (QW) from Day 8 to Day 78. |
| FG002 | PF-06741086 450 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 450 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| FG003 | PF-06741086 300 mg SC QW Inhibitor | Participants with inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline analysis population included all participants who received at least 1 dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-06741086 300 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| BG001 | PF-06741086 300 mg SC Loading + 150 mg SC QW Non-Inhibitor |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (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 or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator. | The analysis population included all participants who received at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Study Day 1 to Day 113 Visit |
|
113 days
The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-06741086 300 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tooth socket haemorrhage | Gastrointestinal disorders | MedDRA21.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA21.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 2, 2017 | Nov 15, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 20, 2017 | Nov 15, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000656192 | marstacimab |
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| PF-06741086 |
| Biological |
PF-06741086 SC injection |
|
| PF-06741086 | Biological | PF-06741086 SC injection |
|
| PF-06741086 | Biological | PF-06741086 SC injection |
|
| Baseline to Study Day 113 |
| Number of Participants With Abnormal Laboratory Findings-Urinalysis | Urinalysis included: pH, urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, leukocyte esterase, urine erythrocytes, urine leukocytes and bacteria. | Baseline to Study Day 113 Visit |
| Change From Baseline for Globulin by Dose Cohort | Blood samples were obtained to determine globulin level in serum, total globulin was derived as total protein other than albumin. | Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113. |
| Change From Baseline for Prothrombin International Normalized Ratio (PT/INR) by Dose Cohort | Blood samples were obtained to evaluate this ratio. The prothrombin time (PT) is a test that helps evaluate your ability to appropriately form blood clots. The international normalized ratio (INR) is a calculation based on results of a PT that is used to monitor individuals who are being treated with the blood-thinning medication (anticoagulant) warfarin (Coumadin®). | Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113. |
| Change From Baseline for Activated Partial Thromboplastin Time (aPTT) by Dose Cohort | The activated partial thromboplastin time (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 sample were obtained to evaluate aPTT. | Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113. |
| Change From Baseline for Fibrinogen by Dose Cohort | 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. | Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113. |
| Change From Baseline for Antithrombin III by Dose Cohort | Antithrombin (AT) is a protein produced by the liver that helps regulate blood clot formation (i.e., a naturally-occurring mild blood thinner). Blood samples were collected to measure the activity (function) and the amount (quantity) of antithrombin in an individual's blood is used to evaluate the person for excessive blood clotting. | Baseline, Study Day 8, 15, 22 and 29. |
| Change From Baseline for Troponin I by Dose Cohort | Blood samples were collected to measure the level of cardiac-specific troponin I in the blood to help detect heart injury. | Baseline, Study Day 8, 15, 22, 29, 57 and 85. |
| Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Criteria for potentially clinically important findings in vital signs data were defined as: 1) supine systolic blood pressure (BP): value <90 mm Hg or change >=30 mm Hg increase; 2) Supine diastolic BP: value <50 mm Hg or change >=20 mm Hg increase; 3) Supine pulse rate: value <40 beats/min or >120 beats/min. | Baseline to Study Day 113 Visit |
| Number of Participants With Electrocardiogram (ECG) Change Meeting Pre-specified Criteria | Criteria for potentially clinically important changes in ECG were defined as: PR interval baseline >200 msec and increase of >=25%; PR interval baseline <=200 msec and increase of >=50%; QRS interval increase of >=50%. Only the number of participants meeting pre-defined criteria was reported below. | Baseline to Study Day 29 Visit. |
| Number of Participants With Clinically Significant Changes in Physical Examination Findings | Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Clinical significance was judged by the investigator. | Baseline to Study Day 113 Visit |
| Number of Participants With Infusion and Injection Site Reactions | Infusion and injection site reactions included: injection site bruising, injection site erythema, injection site haemorrhage, injection site induration, injection site pain, injection site pruritus, injection site swelling and injection site warmth. Grade of severity was defined as follows: Mild: Transient or mild discomfort (< 48 hours); no medical intervention/therapy required. Moderate: Mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required. Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible. | Baseline to Study Day 113 Visit |
| Pre-treatment: within 6 months prior to study enrollment; On-study: Day 1 to 9 days after the last dose (Day 78) |
| Plasma PF-06741086 Concentrations | Plasma PF-06741086 concentrations were analyzed using a validated, sensitive and specific electrochemiluminescence (ECL) method. | pre-dose on Study Day 1, 24hours (h), 72h post Study Day 1 dosing, pre-dose on Study Day 8, 15 and 22, pre-dose on Study Day 29, 24h, 96h post Study Day 29 dosing, pre-dose on Study Day 57, 168h, 840h post Study Day 57 dosing |
| Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06741086 | AUClast was calculated by linear/Log trapezoidal method. | Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing |
| Maximum Plasma Concentration (Cmax) of PF-06741086 | Cmax was observed directly from data. | Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
| Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06741086 | Cmin was observed directly from data. | Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
| Time to Reach Maximum Plasma Concentration (Tmax) of PF-06741086 | Tmax was observed directly from data as time of first occurrence. | Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
| Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of PF-06741086 | The dosing interval tau was 1 week. AUCtau was obtained by linear/log trapezoidal method. | Pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
| Apparent Clearance After Oral Dose (CL/F) of PF-06741086 | CL/F was calculated by dose/AUCtau. | Pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
| Change From Baseline in Total Tissue Factor Pathway Inhibitor (TFPI) | Total amount of tissue factor pathway inhibitor (TFPI) (bound and unbound) in plasma. 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). Human plasma samples were analyzed for total TFPI concentrations using a validated, sensitive and specific high-performance liquid chromatography tandem mass spectrometric method (LC-MS/MS). Mixed model repeated measures (MMRM) was used to analyze the change from baseline on TFPI. | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
| Change From Baseline in Thrombin Generation (TGA) Lag Time | An ex vivo pharmacodynamic measure of thrombin generation (initiation of thrombin generation), the lag time is the time needed to form the first traces of thrombin. | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
| Change From Baseline in Thrombin Generation (TGA) Peak | An ex vivo pharmacodynamic measure of thrombin generation (initiation of thrombin generation). The peak represents the highest thrombin concentration that can be generated. There may be patients who reach the peak faster or slower than others and this may represent hyper- or hypocoagulability, respectively. | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
| Change From Baseline in Endogenous Thrombin Generation (TGA) Potential | An ex vivo pharmacodynamic measure of thrombin generation. The endogenous TGA potential represents the total amount of active thrombin formed during thrombin generation and the peak height the maximal amount of thrombin formed. | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
| Change From Baseline in Prothrombin Fragments 1 + 2 | An in vivo pharmacodynamic measure of thrombin generation (prothrombin cleavage). Prothrombin fragment 1+2 (F 1+2) is the amino terminus fragment of the prothrombin molecule. It is a polypeptide with a half-life of approximately 90 minutes. F 1+2 is released from prothrombin when prothrombin is converted to thrombin by the prothrombinase complex. | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
| Change From Baseline in D-Dimer | An in vivo pharmacodynamic measure of thrombin generation (fibrin degradation). D-dimer is a fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. D-dimer is one of the protein fragments produced when a blood clot gets dissolved in the body. It is normally undetectable or detectable at a very low level unless the body is forming and breaking down blood clots. Then, its level in the blood can significantly rise. | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
| Change From Baseline in Dilute Prothrombin Time | An ex vivo pharmacodynamic measure of thrombin generation (via extrinsic pathway). Clotting time is measured using a dilute prothrombin time reagent consisting of a unique formulation of relipidated recombinant tissue factor and calcium. | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
| Number of Participants Who Tested Positive for Anti-PF-06741086 Antibody (ADA) | Human plasma ADA samples were analyzed for the detection of anti PF-06741086 antibodies by using semi-quantitative electrochemiluminescence (ECL) method. The criterion for positive result of ADA samples was ADA titer >=1.53. Treatment induced are negative prior to dosing and become positive during/after dosing. Treatment boosted are positive prior to dosing but titer increases during/after dosing. | Baseline up to Study Day 113 |
| Number of Participants Who Tested Positive for Neutralizing Antibody (NAb) | Human plasma NAb samples were analyzed for the presence or absence of NAb to PF-06741086 using semi-quantitative electrochemiluminescence (ECL) method. Treatment induced are negative prior to dosing and become positive during/after dosing. Treatment boosted are positive prior to dosing but titer increases during/after dosing. | Baseline up to Study Day 113 |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Pharmacy | Chicago | Illinois | 60612 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Hospital Dr. Sotero del Rio | Santiago | 8207257 | Chile |
| Klinicki bolnicki centar Zagreb | Zagreb | 10000 | Croatia |
| Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne | Gdansk | 80-952 | Poland |
| Phoenix Pharma (Pty) Ltd | Port Elizabeth | Eastern Cape | 6001 | South Africa |
| Haemophilia Comprehensive Care Centre | Johannesburg | Gauteng | 2193 | South Africa |
| UniversitatsSpital Zurich, Klinik fur Hamatologie | Zurich | 8091 | Switzerland |
Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg loading dose on Day 1 and 150 mg subcutaneously (SC) once weekly (QW) from Day 8 to Day 78. |
| BG002 | PF-06741086 450 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 450 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| BG003 | PF-06741086 300 mg SC QW Inhibitor | Participants with inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 |
| PF-06741086 300 mg SC QW Non-Inhibitor |
Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| OG001 | PF-06741086 300 mg SC Loading + 150 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg loading dose on Day 1 and 150 mg subcutaneously (SC) once weekly (QW) from Day 8 to Day 78. |
| OG002 | PF-06741086 450 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 450 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| OG003 | PF-06741086 300 mg SC QW Inhibitor | Participants with inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. |
| OG004 | Overall PF-06741086 300 mg SC | The overall PF-06741086 300 mg SC group combined participants from both the PF-06741086 300 mg SC QW non-inhibitor and inhibitor dose cohorts. |
| OG005 | Total | The total group combined participants from all PF-06741086 cohorts in this study. |
|
|
| Primary | Number of Participants Discontinued From Study Due to TEAEs | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. | The analysis population included all participants who received at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Study Day 1 to Day 113 Visit |
|
|
|
| Primary | Number of Participants With Abnormal Laboratory Findings-Hematology | Hematology evaluation included: hemoglobin, hematocrit, erythrocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils and monocytes. Predefined criteria for hemoglobin and hematocrit: <0.8*lower limit of normal (LLN) or <0.8*Baseline(Baseline <1.0*LLN); for platelets: <100,000*10^3/mm^3 or <= 0.77*Baseline (Baseline <1.0*LLN). | This analysis population included all participants who received at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Baseline to Study Day 113 Visit |
|
|
|
| Primary | Number of Participants With Abnormal Laboratory Findings-Clinical Chemistry | Clinical chemistry evaluation included bilirubin, direct and indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, triglycerides, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase, troponin I, cholesterol and fibrinogen. | This analysis population included all participants who received at least 1 dose of investigational product. Number analyzed refers to number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | Baseline to Study Day 113 |
|
|
|
| Primary | Number of Participants With Abnormal Laboratory Findings-Urinalysis | Urinalysis included: pH, urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, leukocyte esterase, urine erythrocytes, urine leukocytes and bacteria. | This analysis population included all participants who received at least 1 dose of investigational product. Number analyzed refers to number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | Baseline to Study Day 113 Visit |
|
|
|
| Primary | Change From Baseline for Globulin by Dose Cohort | Blood samples were obtained to determine globulin level in serum, total globulin was derived as total protein other than albumin. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | Mean | Standard Deviation | gram/liter | Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113. |
|
|
|
| Primary | Change From Baseline for Prothrombin International Normalized Ratio (PT/INR) by Dose Cohort | Blood samples were obtained to evaluate this ratio. The prothrombin time (PT) is a test that helps evaluate your ability to appropriately form blood clots. The international normalized ratio (INR) is a calculation based on results of a PT that is used to monitor individuals who are being treated with the blood-thinning medication (anticoagulant) warfarin (Coumadin®). | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | Mean | Standard Deviation | Ratio | Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113. |
|
|
|
| Primary | Change From Baseline for Activated Partial Thromboplastin Time (aPTT) by Dose Cohort | The activated partial thromboplastin time (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 sample were obtained to evaluate aPTT. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | Mean | Standard Deviation | seconds | Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113. |
|
|
|
| Primary | Change From Baseline for Fibrinogen by Dose Cohort | 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. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | Mean | Standard Deviation | milligram/deciliter | Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113. |
|
|
|
| Primary | Change From Baseline for Antithrombin III by Dose Cohort | Antithrombin (AT) is a protein produced by the liver that helps regulate blood clot formation (i.e., a naturally-occurring mild blood thinner). Blood samples were collected to measure the activity (function) and the amount (quantity) of antithrombin in an individual's blood is used to evaluate the person for excessive blood clotting. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | Mean | Standard Deviation | Percentage of activity of AT in plasma | Baseline, Study Day 8, 15, 22 and 29. |
|
|
|
| Primary | Change From Baseline for Troponin I by Dose Cohort | Blood samples were collected to measure the level of cardiac-specific troponin I in the blood to help detect heart injury. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | Mean | Standard Deviation | nanogram/milliliter | Baseline, Study Day 8, 15, 22, 29, 57 and 85. |
|
|
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| Primary | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Criteria for potentially clinically important findings in vital signs data were defined as: 1) supine systolic blood pressure (BP): value <90 mm Hg or change >=30 mm Hg increase; 2) Supine diastolic BP: value <50 mm Hg or change >=20 mm Hg increase; 3) Supine pulse rate: value <40 beats/min or >120 beats/min. | This analysis population included all participants who received at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Baseline to Study Day 113 Visit |
|
|
|
| Primary | Number of Participants With Electrocardiogram (ECG) Change Meeting Pre-specified Criteria | Criteria for potentially clinically important changes in ECG were defined as: PR interval baseline >200 msec and increase of >=25%; PR interval baseline <=200 msec and increase of >=50%; QRS interval increase of >=50%. Only the number of participants meeting pre-defined criteria was reported below. | This analysis population included all participants who received at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Baseline to Study Day 29 Visit. |
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|
| Primary | Number of Participants With Clinically Significant Changes in Physical Examination Findings | Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Clinical significance was judged by the investigator. | This analysis population included all participants who received at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Baseline to Study Day 113 Visit |
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|
| Primary | Number of Participants With Infusion and Injection Site Reactions | Infusion and injection site reactions included: injection site bruising, injection site erythema, injection site haemorrhage, injection site induration, injection site pain, injection site pruritus, injection site swelling and injection site warmth. Grade of severity was defined as follows: Mild: Transient or mild discomfort (< 48 hours); no medical intervention/therapy required. Moderate: Mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required. Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible. | This analysis population included all participants who received at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Baseline to Study Day 113 Visit |
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|
|
| Secondary | Annualized Bleeding Rate (ABR) | Pre-treatment ABR = number of bleeding episodes within 6 months prior to study enrollment (total number of bleeding episodes in hemophilia history CRF) × 2; On-study ABR = number of bleeding episodes occurred within 9 days after the last dose / ([last dose date + 9 - first dose date + 1] / 365.25) The historical On Demand group was constructed using the following internal Pfizer studies: ReFacto AF 3082B2-4432 (B1831004), BeneFIX B1821010, and BeneFIX 3090A1-400 (B1821004). Participants who were on On Demand treatment in B1831004, as well as data from the On Demand period in B1821004 and B1821010 were used to construct the historical On Demand group. The resulting dataset were further filtered to match the key inclusion/exclusion criteria of Study B7841002 based on age and factor activity (18 <=age <=65 and factor activity <=1%). | This efficacy analysis was conducted in the Per Protocol Analysis Set (PPAS) that included all participants who received at least 1 dose of investigational product and did not have any major protocol deviations. | Posted | Mean | Standard Deviation | Bleeding episodes per year | Pre-treatment: within 6 months prior to study enrollment; On-study: Day 1 to 9 days after the last dose (Day 78) |
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|
|
| Secondary | Plasma PF-06741086 Concentrations | Plasma PF-06741086 concentrations were analyzed using a validated, sensitive and specific electrochemiluminescence (ECL) method. | The PK concentration population included all enrolled participants treated who had at least 1 quantifiable concentration. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | Mean | Standard Deviation | nanogram/milliliter | pre-dose on Study Day 1, 24hours (h), 72h post Study Day 1 dosing, pre-dose on Study Day 8, 15 and 22, pre-dose on Study Day 29, 24h, 96h post Study Day 29 dosing, pre-dose on Study Day 57, 168h, 840h post Study Day 57 dosing |
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|
|
| Secondary | Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06741086 | AUClast was calculated by linear/Log trapezoidal method. | The PK parameter analysis population included all enrolled participants treated who had at least 1 quantifiable concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour/milliliter | Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing |
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|
| Secondary | Maximum Plasma Concentration (Cmax) of PF-06741086 | Cmax was observed directly from data. | The PK parameter analysis population included all enrolled participants treated who had at least 1 quantifiable concentration. Number analyzed refers to number of participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter | Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
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|
| Secondary | Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06741086 | Cmin was observed directly from data. | The PK parameter analysis population included all enrolled participants treated who had at least 1 quantifiable concentration. Number analyzed refers to number of participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter | Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
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|
| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of PF-06741086 | Tmax was observed directly from data as time of first occurrence. | The PK parameter analysis population included all enrolled participants treated who had at least 1 quantifiable concentration. Number analyzed refers to number of participants evaluable for specified rows. | Posted | Median | Full Range | hours | Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing, pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
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|
| Secondary | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of PF-06741086 | The dosing interval tau was 1 week. AUCtau was obtained by linear/log trapezoidal method. | The PK parameter analysis population included all enrolled participants treated who had at least 1 quantifiable concentration and in whom at least 1 of the PK parameters of interest was calculated. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour/milliliter | Pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
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| Secondary | Apparent Clearance After Oral Dose (CL/F) of PF-06741086 | CL/F was calculated by dose/AUCtau. | The PK parameter analysis population included all enrolled participants treated who had at least 1 quantifiable concentration and in whom at least 1 of the PK parameters of interest was calculated. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliter/hour | Pre-dose on Day 29, 24 and 96 hours post Day 29 dosing |
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| Secondary | Change From Baseline in Total Tissue Factor Pathway Inhibitor (TFPI) | Total amount of tissue factor pathway inhibitor (TFPI) (bound and unbound) in plasma. 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). Human plasma samples were analyzed for total TFPI concentrations using a validated, sensitive and specific high-performance liquid chromatography tandem mass spectrometric method (LC-MS/MS). Mixed model repeated measures (MMRM) was used to analyze the change from baseline on TFPI. | The analysis population included all enrolled participants who received at least 1 dose of study medication and had a baseline measurement and at least 1 post-dose measurement for at least 1 pharmacodynamic endpoint. | Posted | Mean | Standard Deviation | nanogram/milliliter | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
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| Secondary | Change From Baseline in Thrombin Generation (TGA) Lag Time | An ex vivo pharmacodynamic measure of thrombin generation (initiation of thrombin generation), the lag time is the time needed to form the first traces of thrombin. | The analysis population included all enrolled participants who received at least 1 dose of study medication and had a baseline measurement and at least 1 post-dose measurement for at least 1 pharmacodynamic endpoint. | Posted | Mean | Standard Deviation | minutes | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
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|
| Secondary | Change From Baseline in Thrombin Generation (TGA) Peak | An ex vivo pharmacodynamic measure of thrombin generation (initiation of thrombin generation). The peak represents the highest thrombin concentration that can be generated. There may be patients who reach the peak faster or slower than others and this may represent hyper- or hypocoagulability, respectively. | The analysis population included all enrolled participants who received at least 1 dose of study medication and had a baseline measurement and at least 1 post-dose measurement for at least 1 pharmacodynamic endpoint. | Posted | Mean | Standard Deviation | nanomole | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
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|
| Secondary | Change From Baseline in Endogenous Thrombin Generation (TGA) Potential | An ex vivo pharmacodynamic measure of thrombin generation. The endogenous TGA potential represents the total amount of active thrombin formed during thrombin generation and the peak height the maximal amount of thrombin formed. | The analysis population included all enrolled participants who received at least 1 dose of study medication and had a baseline measurement and at least 1 post-dose measurement for at least 1 pharmacodynamic endpoint. | Posted | Mean | Standard Deviation | nanomole*minute | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
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| Secondary | Change From Baseline in Prothrombin Fragments 1 + 2 | An in vivo pharmacodynamic measure of thrombin generation (prothrombin cleavage). Prothrombin fragment 1+2 (F 1+2) is the amino terminus fragment of the prothrombin molecule. It is a polypeptide with a half-life of approximately 90 minutes. F 1+2 is released from prothrombin when prothrombin is converted to thrombin by the prothrombinase complex. | The analysis population included all enrolled participants who received at least 1 dose of study medication and had a baseline measurement and at least 1 post-dose measurement for at least 1 pharmacodynamic endpoint. | Posted | Mean | Standard Deviation | picomole/liter | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
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|
| Secondary | Change From Baseline in D-Dimer | An in vivo pharmacodynamic measure of thrombin generation (fibrin degradation). D-dimer is a fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. D-dimer is one of the protein fragments produced when a blood clot gets dissolved in the body. It is normally undetectable or detectable at a very low level unless the body is forming and breaking down blood clots. Then, its level in the blood can significantly rise. | The analysis population included all enrolled participants who received at least 1 dose of study medication and had a baseline measurement and at least 1 post-dose measurement for at least 1 pharmacodynamic endpoint. | Posted | Mean | Standard Deviation | microgram/milliliter | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
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| Secondary | Change From Baseline in Dilute Prothrombin Time | An ex vivo pharmacodynamic measure of thrombin generation (via extrinsic pathway). Clotting time is measured using a dilute prothrombin time reagent consisting of a unique formulation of relipidated recombinant tissue factor and calcium. | The analysis population included all enrolled participants who received at least 1 dose of study medication and had a baseline measurement and at least 1 post-dose measurement for at least 1 pharmacodynamic endpoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Study Day 2, 4, 8, 15, 22, 29, 30, 33, 57, 85 and 113 |
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| Secondary | Number of Participants Who Tested Positive for Anti-PF-06741086 Antibody (ADA) | Human plasma ADA samples were analyzed for the detection of anti PF-06741086 antibodies by using semi-quantitative electrochemiluminescence (ECL) method. The criterion for positive result of ADA samples was ADA titer >=1.53. Treatment induced are negative prior to dosing and become positive during/after dosing. Treatment boosted are positive prior to dosing but titer increases during/after dosing. | This analysis population included all participants who received at least 1 dose of investigational drug. | Posted | Count of Participants | Participants | Baseline up to Study Day 113 |
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|
| Secondary | Number of Participants Who Tested Positive for Neutralizing Antibody (NAb) | Human plasma NAb samples were analyzed for the presence or absence of NAb to PF-06741086 using semi-quantitative electrochemiluminescence (ECL) method. Treatment induced are negative prior to dosing and become positive during/after dosing. Treatment boosted are positive prior to dosing but titer increases during/after dosing. | Only positive ADA samples and the corresponding baseline sample were tested in the NAb assay. | Posted | Count of Participants | Participants | Baseline up to Study Day 113 |
|
|
|
| 0 |
| 7 |
| 1 |
| 7 |
| 6 |
| 7 |
| EG001 | PF-06741086 300 mg SC Loading + 150 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg loading dose on Day 1 and 150 mg subcutaneously (SC) once weekly (QW) from Day 8 to Day 78. | 0 | 6 | 1 | 6 | 4 | 6 |
| EG002 | PF-06741086 450 mg SC QW Non-Inhibitor | Participants without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 450 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG003 | PF-06741086 300 mg SC QW Inhibitor | Participants with inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in this cohort received PF-06741086 300 mg subcutaneously (SC) once weekly (QW) from Day 1 to Day 78. | 0 | 7 | 1 | 7 | 4 | 7 |
| EG004 | Overall PF-06741086 300 mg SC | The overall PF-06741086 300 mg SC group combined participants from both the PF-06741086 300 mg SC QW non-inhibitor and inhibitor dose cohorts. | 0 | 14 | 2 | 14 | 10 | 14 |
| EG005 | Total | The total group combined participants from all PF-06741086 cohorts in this study. | 0 | 26 | 4 | 26 | 20 | 26 |
| Cholelithiasis | Hepatobiliary disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA21.1 | Non-systematic Assessment |
|
| Physical assault | Social circumstances | MedDRA21.1 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Injection site bruising | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Injection site haemorrhage | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Injection site induration | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Injection site pain | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Injection site warmth | General disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA21.1 | Non-systematic Assessment |
|
| Periodontitis | Infections and infestations | MedDRA21.1 | Non-systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA21.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA21.1 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA21.1 | Non-systematic Assessment |
|
| Occupational exposure to product | Injury, poisoning and procedural complications | MedDRA21.1 | Non-systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA21.1 | Non-systematic Assessment |
|
| Blood fibrinogen decreased | Investigations | MedDRA21.1 | Non-systematic Assessment |
|
| Fibrin D dimer increased | Investigations | MedDRA21.1 | Non-systematic Assessment |
|
| Prothrombin time prolonged | Investigations | MedDRA21.1 | Non-systematic Assessment |
|
| Troponin I increased | Investigations | MedDRA21.1 | Non-systematic Assessment |
|
| Troponin increased | Investigations | MedDRA21.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Haemophilic arthropathy | Musculoskeletal and connective tissue disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Cerebrospinal fluid leakage | Nervous system disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA21.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA21.1 | Non-systematic Assessment |
|
Not provided
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| Treatment-related TEAE |
|
| Hematocrit meeting pre-defined criteria |
|
| Erythrocytes <0.8*LLN |
|
| Platelets meeting pre-defined criteria |
|
| Leukocytes <0.6*LLN |
|
| Leukocytes >1.5*upper limit of normal (ULN) |
|
| Lymphocytes <0.8*LLN |
|
| Lymphocytes >1.2*ULN |
|
| Neutrophils <0.8*LLN |
|
| Neutrophils >1.2*ULN |
|
| Basophils >1.2*ULN |
|
| Eosinophils >1.2*ULN |
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| Monocytes >1.2*ULN |
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|
| Direct Bilirubin >1.5*ULN |
|
|
| Indirect Bilirubin >1.5*ULN |
|
|
| Aspartate Aminotransferase >3.0*ULN |
|
|
| Alanine Aminotransferase >3.0*ULN |
|
|
| Gamma Glutamyl Transferase >3.0*ULN |
|
|
| Alkaline Phosphatase |
|
|
| Protein <0.8*LLN |
|
|
| Protein >1.2*ULN |
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|
| Albumin <0.8*LLN |
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|
| Albumin >1.2*ULN |
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| Urea Nitrogen >1.3*ULN |
|
|
| Creatinine >1.3*ULN |
|
|
| Urate >1.2*ULN |
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|
| Triglycerides >1.3*ULN |
|
|
| Sodium <0.95*LLN |
|
|
| Sodium >1.05*ULN |
|
|
| Potassium <0.9*LLN |
|
|
| Potassium >1.1*ULN |
|
|
| Chloride <0.9*LLN |
|
|
| Chloride >1.1*ULN |
|
|
| Calcium <0.9*LLN |
|
|
| Calcium >1.1*ULN |
|
|
| Bicarbonate <0.9*LLN |
|
|
| Bicarbonate >1.1*ULN |
|
|
| Glucose <0.6*LLN |
|
|
| Glucose >1.5*ULN |
|
|
| Creatine Kinase >2.0*ULN |
|
|
| Troponin I >1.0*ULN |
|
|
| Cholesterol >1.3*ULN |
|
|
| Fibrinogen <=0.5*LLN or <=0.5*baseline |
|
|
|
| pH (Scalar) >8 |
|
|
| Urine glucose >=1 |
|
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| Ketones (Scalar) >=1 |
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| Urine protein >=1 |
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| Urine hemoglobin (Scalar) >=1 |
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| Urobilinogen >=1 |
|
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| Urine bilirubin (Scalar) >=1 |
|
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| Nitrite (Scalar) >=1 |
|
|
| Leukocyte esterase (Scalar) >=1 |
|
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| Urine erythrocytes (/HPF) >=20 |
|
|
| Urine leukocytes (/HPF) >=20 |
|
|
| Bacteria (/HPF) >20 |
|
|
|
| Globulin, Change at Day 15 |
|
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| Globulin, Study Day 22 |
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| Globulin, Change at Day 29 |
|
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| Globulin, Change at Day 57 |
|
|
| Globulin, Change at Day 85 |
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| Globulin, Change at Day 113 |
|
|
|
| PT/INR, Change at Day 15 |
|
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| PT/INR, Change at Day 22 |
|
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| PT/INR, Change at Day 29 |
|
|
| PT/INR, Change at Day 57 |
|
|
| PT/INR, Change at Day 85 |
|
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| PT/INR, Change at Day 113 |
|
|
|
| aPTT, Change at Day 15 |
|
|
| aPTT, Change at Day 22 |
|
|
| aPTT, Change at Day 29 |
|
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| aPTT, Change at Day 57 |
|
|
| aPTT, Change at Day 85 |
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|
| aPTT, Change at Day 113 |
|
|
|
| Fibrinogen, Change at Day 15 |
|
|
| Fibrinogen, Change at Day 22 |
|
|
| Fibrinogen, Change at Day 29 |
|
|
| Fibrinogen, Change at Day 57 |
|
|
| Fibrinogen, Change at Day 85 |
|
|
| Fibrinogen, Change at Day 113 |
|
|
|
| Antithrombin III, Change at Day 15 |
|
|
| Antithrombin III, Change at Day 22 |
|
|
| Antithrombin III, Change at Day 29 |
|
|
|
| Troponin I, Change at Day 15 |
|
|
| Troponin I, Change at Day 22 |
|
|
| Troponin I, Change at Day 29 |
|
|
| Troponin I, Change at Day 57 |
|
|
| Troponin I, Change at Day 85 |
|
|
| Supine systolic BP change >=30 mm Hg increase |
|
| Supine diastolic BP value <50 mm Hg |
|
| Supine diastolic BP change >=20 mm Hg increase |
|
| Supine pulse rate value <40 beats/min |
|
| Supine pulse rate value >120 beats/min |
|
| Treatment-related Mild |
|
| All-causality Moderate |
|
| Treatment-related Moderate |
|
| All-causality Severe |
|
| Treatment-related Severe |
|
| On-Study |
|
| The comparator was the Historical on Demand Group | Negative Binomial Model | 0.0001 | ratio | 0.05 | 2-Sided | 80 | 0.02 | 0.14 | Superiority | Prophylactic treatment with PF-06741086 will be considered superior to On Demand treatment with respect to ABR reduction if 1) the upper limit of the 2-sided 80%CI of the ratio of ABR in PF/historical On Demand is <1 and 2) the estimate of the ratio of ABR in PF/historical On Demand ≤0.3. Drug will be considered not superior to On Demand treatment if the lower limit of the 2-sided 80%CI of the ratio of PF/historical On Demand >0.3. |
| The comparator was the Historical on Demand Group | Negative Binomial Model | 0.0002 | ratio | 0.15 | 2-Sided | 80 | 0.08 | 0.29 | Superiority | Prophylactic treatment with PF-06741086 will be considered superior to On Demand treatment with respect to ABR reduction if 1) the upper limit of the 2-sided 80%CI of the ratio of ABR in PF/historical On Demand is <1 and 2) the estimate of the ratio of ABR in PF/historical On Demand ≤0.3. Drug will be considered not superior to On Demand treatment if the lower limit of the 2-sided 80%CI of the ratio of PF/historical On Demand >0.3. |
| The comparator was the Historical on Demand Group | Negative Binomial Model | 0.0005 | ratio | 0.03 | 2-Sided | 80 | 0.01 | 0.10 | Superiority | Prophylactic treatment with PF-06741086 will be considered superior to On Demand treatment with respect to ABR reduction if 1) the upper limit of the 2-sided 80%CI of the ratio of ABR in PF/historical On Demand is <1 and 2) the estimate of the ratio of ABR in PF/historical On Demand ≤0.3. Drug will be considered not superior to On Demand treatment if the lower limit of the 2-sided 80%CI of the ratio of PF/historical On Demand >0.3. |
| The comparator was the Historical on Demand Group | Negative Binomial Model | <0.0001 | ratio | 0.09 | 2-Sided | 80 | 0.05 | 0.16 | Superiority | Prophylactic treatment with PF-06741086 will be considered superior to On Demand treatment with respect to ABR reduction if 1) the upper limit of the 2-sided 80%CI of the ratio of ABR in PF/historical On Demand is <1 and 2) the estimate of the ratio of ABR in PF/historical On Demand ≤0.3. Drug will be considered not superior to On Demand treatment if the lower limit of the 2-sided 80%CI of the ratio of PF/historical On Demand >0.3. |
| On-Study versus Pre-Treatment | Negative Binomial Model | <0.0001 | ratio | 0.18 | 2-Sided | 80 | 0.11 | 0.31 | Superiority |
| On-Study versus Pre-Treatment | Negative Binomial Model | 0.0002 | ratio | 0.10 | 2-Sided | 80 | 0.04 | 0.22 | Superiority |
| On-Study versus Pre-Treatment | Negative Binomial Model | 0.0154 | ratio | 0.20 | 2-Sided | 80 | 0.09 | 0.47 | Superiority |
| On-Study versus Pre-Treatment | Negative Binomial Model | 0.0005 | ratio | 0.04 | 2-Sided | 80 | 0.01 | 0.14 | Superiority |
| On-Study versus Pre-Treatment | Negative Binomial Model | <0.0001 | ratio | 0.12 | 2-Sided | 80 | 0.08 | 0.20 | Superiority |
| 24h post Day 1 dosing |
|
|
| 72h post Day 1 dosing |
|
|
| Pre-dose on Day 8 |
|
|
| Pre-dose on Day 15 |
|
|
| Pre-dose on Day 22 |
|
|
| Pre-dose on Day 29 |
|
|
| 24h post Day 29 dosing |
|
|
| 96h post Day 29 dosing |
|
|
| Pre-dose on Day 57 |
|
|
| 168h post Day 57 dosing |
|
|
| 840h post Day 57 dosing |
|
|
|
| Cmax, Day 29 |
|
|
|
| Cmin, Day 29 |
|
|
|
| Tmax, Day 29 |
|
|
|
| TFPI, Change at Day 4 |
|
|
| TFPI, Change at Day 8 |
|
|
| TFPI, Change at Day 15 |
|
|
| TFPI, Change at Day 22 |
|
|
| TFPI, Change at Day 29 |
|
|
| TFPI, Change at Day 30 |
|
|
| TFPI, Change at Day 33 |
|
|
| TFPI, Change at Day 57 |
|
|
| TFPI, Change at Day 85 |
|
|
| TFPI, Change at Day 113 |
|
|
|
| TGA lag time, Change at Day 4 |
|
|
| TGA lag time, Change at Day 8 |
|
|
| TGA lag time, Change at Day 15 |
|
|
| TGA lag time, Change at Day 22 |
|
|
| TGA lag time, Change at Day 29 |
|
|
| TGA lag time, Change at Day 30 |
|
|
| TGA lag time, Change at Day 33 |
|
|
| TGA lag time, Change at Day 57 |
|
|
| TGA lag time,Change at Day 85 |
|
|
| TGA lag time, Change at Day 113 |
|
|
|
| TGA peak, Change at Day 4 |
|
|
| TGA peak, Change at Day 8 |
|
|
| TGA peak, Change at Day 15 |
|
|
| TGA peak, Change at Day 22 |
|
|
| TGA peak, Change at Day 29 |
|
|
| TGA peak, Change at Day 30 |
|
|
| TGA peak, Change at Day 33 |
|
|
| TGA peak, Change at Day 57 |
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|
| TGA peak, Change at Day 85 |
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|
| TGA peak, Change at Day 113 |
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|
|
| Endogenous TGA Potential, Change at Day 4 |
|
|
| Endogenous TGA Potential, Change at Day 8 |
|
|
| Endogenous TGA Potential, Change at Day 15 |
|
|
| Endogenous TGA Potential, Change at Day 22 |
|
|
| Endogenous TGA Potential, Change at Day 29 |
|
|
| Endogenous TGA Potential, Change at Day 30 |
|
|
| Endogenous TGA Potential, Change at Day 33 |
|
|
| Endogenous TGA Potential, Change at Day 57 |
|
|
| Endogenous TGA Potential, Change at Day 85 |
|
|
| Endogenous TGA Potential, Change at Day 113 |
|
|
|
| Prothrombin fragments 1 + 2, Change at Day 4 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 8 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 15 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 22 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 29 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 30 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 33 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 57 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 85 |
|
|
| Prothrombin fragments 1 + 2, Change at Day 113 |
|
|
|
| D-dimer, Change at Day 4 |
|
|
| D-dimer, Change at Day 8 |
|
|
| D-dimer, Change at Day 15 |
|
|
| D-dimer, Change at Day 22 |
|
|
| D-dimer, Change at Day 29 |
|
|
| D-dimer, Change at Day 30 |
|
|
| D-dimer, Change at Day 33 |
|
|
| D-dimer, Change at Day 57 |
|
|
| D-dimer, Change at Day 85 |
|
|
| D-dimer, Change at Day 113 |
|
|
|
| Dilute prothrombin Time, Change at Day 4 |
|
|
| Dilute prothrombin Time, Change at Day 8 |
|
|
| Dilute prothrombin Time, Change at Day 15 |
|
|
| Dilute prothrombin Time, Change at Day 22 |
|
|
| Dilute prothrombin Time, Change at Day 29 |
|
|
| Dilute prothrombin Time, Change at Day 30 |
|
|
| Dilute prothrombin Time, Change at Day 33 |
|
|
| Dilute prothrombin Time, Change at Day 57 |
|
|
| Dilute prothrombin TIme, Change at Day 85 |
|
|
| Dilute prothrombin Time, Change at Day 113 |
|
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| Participants with treatment induced ADA incidence |
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| Participants with treatment boosted ADA incidence |
|
| Participants with treatment induced NAb incidence |
|
| Participants with treatment boosted NAb incidence |
|