PF-06741086 Long-term Treatment in Severe Hemophilia

A MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE LONG-TERM SAFETY, TOLERABILITY AND EFFICACY OF SUBCUTANEOUS PF-06741086 IN SUBJECTS WITH SEVERE HEMOPHILIA

This study is designed to evaluate the safety, tolerability and efficacy of long-term treatment with PF-06741086 in subjects with severe hemophilia who participated in the 3-month Phase 1b/2 B7841002 study. Additionally, de novo subjects will be recruited into this study.

Study Overview

• Status: Completed
• Conditions: Hemophilia A or B
• Intervention / Treatment: Biological: PF-06741086

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SAO Paulo
    • Campinas, SAO Paulo, Brazil, 13083-878
      • Centro de Hematologia e Hemoterapia de Campinas- Hemocentro de Campinas
• Chile
  • Puente ALTO
    • Santiago, Puente ALTO, Chile, 8207257
      • Hospital Dr. Sótero del Río
• Croatia
  • Zagreb, Croatia, 10000
    • Klinički bolnički centar Zagreb
• Poland
  • Gdansk, Poland, 80-214
    • Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne
• South Africa
  • Eastern CAPE
    • Port Elizabeth, Eastern CAPE, South Africa, 6001
      • Phoenix Pharma (Pty) Ltd
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Charlotte Maxeke Johannesburg Academic Hospital
• Switzerland
  • Zurich, Switzerland, 8091
    • Universitatsspital Zurich
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UC Denver Hemophilia and Thrombosis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 74 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Severe hemophilia A or B (Factor VIII or Factor IX activity ≤ 1%)
• Subjects enrolled as Factor VIII or Factor IX inhibitor patients must have a positive inhibitor test result (above the upper limit of normal) at the local laboratory and must receive a bypass agent as primary treatment for bleeding episodes.
• Episodic (on-demand) treatment regimen prior to screening
• At least 6 acute bleeding episodes during the 6-month period prior to screening

Exclusion Criteria:

• Known coronary artery, thrombotic, or ischemic disease
• Concomitant treatment with activated prothrombin complex concentrate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PF-06741086 (Cohort 1)	Biological: PF-06741086; PF-06741086 subcutaneous injection
EXPERIMENTAL: PF-06741086 (Cohort 2)	Biological: PF-06741086; PF-06741086 subcutaneous injection
EXPERIMENTAL: PF-06741086 (Cohort 3)	Biological: PF-06741086; PF-06741086 subcutaneous injection
EXPERIMENTAL: PF-06741086 (Cohort 4)	Biological: PF-06741086; PF-06741086 subcutaneous injection
EXPERIMENTAL: PF-06741086 (Cohort 5)	Biological: PF-06741086; PF-06741086 subcutaneous injection
EXPERIMENTAL: PF-06741086 (Cohort 6)	Biological: PF-06741086; PF-06741086 subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), TEAEs by Severity, and Serious Adverse Events (SAEs) (All Causality and Treatment-Related)	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. Treatment-related TEAEs were determined by the investigator. Grades 3 AEs were severe and undesirable adverse events. Grades 4 AEs were life threatening or disabling adverse events.	Day 1 up to Day 393
Number of Participants With Abnormal Laboratory Findings Without Regard to Baseline Abnormality (Including Hematology, Serum Chemistry, and Urinalysis)	Following parameters were analyzed for laboratory examination: hematology, clinical chemistry, and urinalysis. The hematology parameters and pre-defined criteria included: neutrophils (10^3/millimeter[mm]^3) <0.8*lower limit of normal (LLN), and basophils (10^3/mm^3) >1.2*upper limit of normal (ULN). The clinical chemistry parameter and pre-defined criteria included: bilirubin (milligrams [mg]/decilitre [dL]) >1.5 ULN, aspartate aminotransferase (units [U]/liter [L]) >3.0 ULN, glucose (mg/dL) >1.5*ULN. The urinalysis parameter and pre-defined criteria included: urine glucose ≥1, ketones (scalar) ≥1, urine protein ≥1, urine hemoglobin (scalar) ≥1, and hyaline casts per low power field (/LPF). Participants met criteria at any time point were included.	Hematology and serum chemistry: Baseline, Days 1, 29, 57, 85, 169, 253, and 365 visits. Urinalysis: Baseline, Days 1, 85, 169, 253, and 365 visits.
Number of Participants With Changes From Baseline in Vital Signs Measurements Meeting the Pre-Defined Categorical Summarization Criteria	Following parameters were analyzed for vital sign examination: blood pressure (BP), pulse rate (PR), temperature, respiration rate. Categorical vital signs: Temperature >38.5 degree(s) Celsius (℃), Supine PR: <40 or >120 beats per minute (BPM), Systolic BP: <90 mm Hg, >=30 mm Hg change from baseline, Diastolic BP: <50 mm Hg, >=20 mm Hg change from baseline.	Baseline, Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365 and 393 visits.
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters Meeting the Pre-defined Categorical Summarization Criteria	Baseline was defined as the average of triplicate ECG measurements collected prior to dosing on Day 1 in B7841003. Criteria for potentially clinically important changes in ECG were defined as: PR interval value >=300 millisecond (msec); PR interval baseline >200 msec and change >=25%; PR interval baseline <=200 msec and change >=50%; QRS complex value >=140 msec and change >=50%; QTcF value >=450 msec and change >=30 msec. Only the number of participants meeting pre-defined criteria was reported below.	Baseline, Days 1 and 29 visits
Number of Participants With Abnormalities in Physical Examination Findings	Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The limited or abbreviated physical examination was focused on general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. For measuring weight, a scale with appropriate range and resolution was used and must have been placed on a stable, flat surface. Participants removed shoes, bulky layers of clothing, and jackets so that only light clothing remains. They also removed the contents of their pockets and remain still during measurement of weight.	Day 1 to Day 393
Number of Participants With Injection Site Reactions	Injection site reactions included but were not limited to: erythema, induration, ecchymosis, pain and pruritus. 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.	Day 1 to Day 365, and Day 393 visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleeding Rate (ABR)	The ABR was calculated as ([number of bleeding events × 365.25] / observed treatment period in days)	Day 1 to Day 365, and Day 393 visit. Pre-Treatment summarized the data up to 6 months prior to participation in B7841003 for de novo participants and up to 6 months prior to participation in B7841002 for roll over participants.

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Mahlangu J, Luis Lamas J, Cristobal Morales J, Malan DR, Teeter J, Charnigo RJ, Hwang E, Arkin S. Long-term safety and efficacy of the anti-tissue factor pathway inhibitor marstacimab in participants with severe haemophilia: Phase II study results. Br J Haematol. 2023 Jan;200(2):240-248. doi: 10.1111/bjh.18495. Epub 2022 Oct 11.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 30, 2018
• Primary Completion (ACTUAL): August 5, 2020
• Study Completion (ACTUAL): August 5, 2020

Study Registration Dates

• First Submitted: November 30, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (ACTUAL): December 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 6, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: hemophilia
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: B7841003; 2017-001255-31 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No