PF-06741086 Multiple Dose Study in Severe Hemophilia

NCT02974855 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: B78410022016-001885-27
• Study Type: interventional
• Target: 27
• Locations: 6 countries
• Sites: 10

Brief Summary

This study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of multiple subcutaneous and/or intravenous doses of PF-06741086 in subjects with severe hemophilia.

Conditions

Hemophilia A or B

Keywords

hemophilia

Outcome Measures

Primary Outcomes (15)

• 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.

  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

Secondary Outcomes (17)

• Annualized Bleeding Rate (ABR)

  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

  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

  Pre-dose on Day 1, 24 and 96 hours post Day 1 dosing

• Maximum Plasma Concentration (Cmax) of PF-06741086

  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

  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

Study Arms (4)

PF-06741086 (Cohort 1)

EXPERIMENTAL

Biological: PF-06741086

PF-06741086 (Cohort 2)

EXPERIMENTAL

Biological: PF-06741086

PF-06741086 (Cohort 3)

EXPERIMENTAL

Biological: PF-06741086

PF-06741086 (Cohort 4)

EXPERIMENTAL

Biological: PF-06741086

Interventions

PF-06741086 BIOLOGICAL

PF-06741086 subcutaneous (SC) injection

PF-06741086 (Cohort 1)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Severe hemophilia A or B (Factor VIII or Factor IX activity ≤ 1%), including patients with inhibitors to Factor VIII or Factor IX
• Episodic (on-demand) treatment regimen prior to screening
• At least 6 acute bleeding episodes during the 6-month period prior to screening

You may not qualify if:

• Known coronary artery, thrombotic, or ischemic disease
• Currently receiving treatment for acute bleeding episodes with APCC and cannot substitute treatment with rFVIIa

Sponsors & Collaborators

• Pfizer: lead

Study Sites (10)

UC Denver Hemophilia and Thrombosis Center - Pharmacy

Aurora, Colorado, 80045, United States

Location

UC Denver Hemophilia and Thrombosis Center

Aurora, Colorado, 80045, United States

Location

Pharmacy

Chicago, Illinois, 60612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Hospital Dr. Sotero del Rio

Santiago, 8207257, Chile

Location

Klinicki bolnicki centar Zagreb

Zagreb, 10000, Croatia

Location

Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Phoenix Pharma (Pty) Ltd

Port Elizabeth, Eastern Cape, 6001, South Africa

Location

Haemophilia Comprehensive Care Centre

Johannesburg, Gauteng, 2193, South Africa

Location

UniversitatsSpital Zurich, Klinik fur Hamatologie

Zurich, 8091, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 35999026 DERIVED

Related Links

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

MeSH Terms

Conditions

Hemophilia A

Interventions

marstacimab

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2016
• First Posted: November 29, 2016
• Study Start: March 8, 2017
• Primary Completion: December 3, 2018
• Study Completion: December 3, 2018
• Last Updated: December 4, 2019
• Results First Posted: December 4, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share

Locations

ZA (2); CH (1); CL (1); PL (1); CR (1); US (4)