PF-06741086 Multiple Dose Study in Severe Hemophilia

Study at a glance

From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A MULTICENTER, OPEN-LABEL, MULTIPLE ASCENDING DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF SUBCUTANEOUS OR INTRAVENOUS PF-06741086 IN SUBJECTS WITH SEVERE HEMOPHILIA

ClinicalTrials.gov ID

NCT02974855

Acronym / sponsor ID

B7841002

Conditions

Hemophilia A or B

Keywords

hemophilia

Phase

Phase 2

Study type

Interventional

Recruitment status

Completed

Enrolment

27 participants (actual)

Lead sponsor

PfizerIndustry (pharma, biotech, devices)

Study start

8 Mar 2017 (actual)

Primary completion

3 Dec 2018 (actual)

Study completion

3 Dec 2018 (actual)

First posted

29 Nov 2016 (estimated)

Results

Posted 4 Dec 2019

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

Prevention

Allocation

Non-randomised

Intervention model

Sequential

Masking

None (open label)

Number of arms

4

Who may qualify

Ages

18 to 64 years

Sex

Male only

Healthy volunteers

Not accepted

Age groups

Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs)

   Time frame: Study Day 1 to Day 113 Visit

   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.

2. Number of Participants Discontinued From Study Due to TEAEs

   Time frame: Study Day 1 to Day 113 Visit

   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.

3. Number of Participants With Abnormal Laboratory Findings-Hematology

   Time frame: Baseline to Study Day 113 Visit

   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).

4. Number of Participants With Abnormal Laboratory Findings-Clinical Chemistry

   Time frame: Baseline to Study Day 113

   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.

5. Number of Participants With Abnormal Laboratory Findings-Urinalysis

   Time frame: Baseline to Study Day 113 Visit

   Urinalysis included: pH, urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, leukocyte esterase, urine erythrocytes, urine leukocytes and bacteria.

6. Change From Baseline for Globulin by Dose Cohort

   Time frame: Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113.

   Blood samples were obtained to determine globulin level in serum, total globulin was derived as total protein other than albumin.

7. Change From Baseline for Prothrombin International Normalized Ratio (PT/INR) by Dose Cohort

   Time frame: Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113.

   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®).

8. Change From Baseline for Activated Partial Thromboplastin Time (aPTT) by Dose Cohort

   Time frame: Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113.

   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.

9. Change From Baseline for Fibrinogen by Dose Cohort

   Time frame: Baseline, Study Day 8, 15, 22, 29, 57, 85 and 113.

   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.

10. Change From Baseline for Antithrombin III by Dose Cohort

    Time frame: Baseline, Study Day 8, 15, 22 and 29.

    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.

11. Change From Baseline for Troponin I by Dose Cohort

    Time frame: Baseline, Study Day 8, 15, 22, 29, 57 and 85.

    Blood samples were collected to measure the level of cardiac-specific troponin I in the blood to help detect heart injury.

12. Number of Participants With Vital Signs Data Meeting Pre-specified Criteria

    Time frame: Baseline to Study Day 113 Visit

    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.

13. Number of Participants With Electrocardiogram (ECG) Change Meeting Pre-specified Criteria

    Time frame: Baseline to Study Day 29 Visit.

    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.

14. Number of Participants With Clinically Significant Changes in Physical Examination Findings

    Time frame: Baseline to Study Day 113 Visit

    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.

15. Number of Participants With Infusion and Injection Site Reactions

    Time frame: Baseline to Study Day 113 Visit

    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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2019.
• 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.
• Derived from this study: PubMed 35999026Mahlangu 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.
• To obtain contact information for a study center near you, click here.Link provided by the sponsor.
• Individual participant dataSharing planned: Yes. 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.

10 sites in 6 countries: see every site and its status.