Hemophilia A and B
Conditions
Keywords
Subcutaneous, Prophylaxis, Non-Inhibitors, Inhibitors
Brief summary
The purpose of this study was to assess the safety and tolerability of multiple doses of a human monoclonal antibody (BAY1093884) given under the skin in subjects with hemophilia A or B. This antibody was intended to protect from bleeds by inhibiting a substance (Tissue Factor Pathway Inhibitor, TFPI) that reduces the ability of the body to form blood clots.
Detailed description
The primary objective of the study was to assess the safety and tolerability of multiple subcutaneous injections of BAY1093884 (anti-TFPI monoclonal antibody, immunoglobulin G2, IgG2) in patients with hemophilia A or B with or without inhibitors.
Interventions
DRUGBefovacimab (BAY1093884)
Once weekly doses until premature termination of the study, subcutaneous injection
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male severe hemophilic patients with undetectable FVIII activity \<1% or FIX activity \<2%, with or without inhibitors (any titer) are eligible. * Subjects with a past history of inhibitors (any inhibitor titer) are eligible. * Age ≥18 years. * Documentation of ≥4 bleeding episodes (any type or location of bleeds, treated or not) within the 6 months prior to screening. * For subjects on prophylaxis: Willingness to interrupt ongoing prophylaxis. * For subjects on immune tolerance induction (ITI): Willingness to interrupt ongoing ITI.
Exclusion criteria
* History of any other coagulation disorder (particularly disseminated intravascular coagulopathy or combined FVIII/FV deficiency) or platelet disorder. * History of diseases related to venous thromboembolic events (e.g., pulmonary embolism, deep vein thrombosis, thrombophlebitis) or thrombotic microangiopathy. * Risk factors for venous or arterial diseases (e.g., uncontrolled hypertension, uncontrolled diabetes). * History of cardiac, coronary and/or arterial peripheral atherosclerotic disease * Platelet count \<100,000/μL. * Human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4+) lymphocyte count of \<200/mm\^3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug-related Treatment-emergent Adverse Events | After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days | An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as treatment-emergent AEs (TEAEs). Drug-related TEAEs were TEAEs that had reasonable causal relationship to the study treatment decided by the investigators. |
| Number of Participants With Serious Treatment-emergent Adverse Events | After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days | A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was lifethreatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. SAEs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as serious treatment-emergent AEs (TESAEs). Drug-related TESAEs were TESAEs that had reasonable causal relationship to the study treatment decided by the investigators. |
| Number of Participants With Treatment-emergent Adverse Events of Special Interest | After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days | Any thromboembolic or thrombotic microangiopathic event or any hypersensitivity reaction was an adverse event of special interest (AESI). AESIs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as treatment-emergent AESIs. |
| Number of Participants With Clinically Relevant Abnormalities in Laboratory Values | After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days | Clinically relevant implied the presence of a clinical sign or symptom that required medical action. |
Countries
Australia, Austria, Bulgaria, France, Hungary, Italy, Japan, New Zealand, South Korea, Taiwan, United Kingdom
Participant flow
Recruitment details
Study was conducted at multiple centers in 11 countries or regions between 24 July 2018 (first subject first visit) and 15 October 2019 (last subject last visit).
Pre-assignment details
Overall, 26 participants were screened. Of them, 1 participant was screen failure and 1 participant could not start subsequent treatment on schedule; 24 participants received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| BAY1093884 100mg Subjects received BAY1093884 100 mg once a week until premature termination of the study | 8 |
| BAY1093884 225mg Subjects received BAY1093884 225 mg once a week until premature termination of the study | 8 |
| BAY1093884 400mg Subjects received BAY1093884 400mg once a week until premature termination of the study | 8 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Premature termination of the study | 7 | 7 | 8 |
| Overall Study | Serious adverse event | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | BAY1093884 100mg | BAY1093884 225mg | BAY1093884 400mg | Total |
|---|---|---|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 14.5 | 43.5 years STANDARD_DEVIATION 15.6 | 43.1 years STANDARD_DEVIATION 5.9 | 43.5 years STANDARD_DEVIATION 12.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 7 / 8 | 6 / 8 | 6 / 8 |
| serious Total, serious adverse events | 1 / 8 | 2 / 8 | 1 / 8 |
Outcome results
Primary
Number of Participants With Clinically Relevant Abnormalities in Laboratory Values
Clinically relevant implied the presence of a clinical sign or symptom that required medical action.
Time frame: After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days
Population: Safety analysis set (SAF): all participants with at least one intake of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BAY1093884 100mg | Number of Participants With Clinically Relevant Abnormalities in Laboratory Values | 0 Participants |
| BAY1093884 225mg | Number of Participants With Clinically Relevant Abnormalities in Laboratory Values | 0 Participants |
| BAY1093884 400mg | Number of Participants With Clinically Relevant Abnormalities in Laboratory Values | 0 Participants |
Primary
Number of Participants With Drug-related Treatment-emergent Adverse Events
An adverse event (AE) was any untoward medical occurrence (i.e., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a participant in the study. Any bleeding event occurring during the study was not documented as an AE because this event was planned to be captured in the assessment of efficacy. AEs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as treatment-emergent AEs (TEAEs). Drug-related TEAEs were TEAEs that had reasonable causal relationship to the study treatment decided by the investigators.
Time frame: After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days
Population: Safety analysis set (SAF): all participants with at least one intake of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BAY1093884 100mg | Number of Participants With Drug-related Treatment-emergent Adverse Events | 1 Participants |
| BAY1093884 225mg | Number of Participants With Drug-related Treatment-emergent Adverse Events | 4 Participants |
| BAY1093884 400mg | Number of Participants With Drug-related Treatment-emergent Adverse Events | 5 Participants |
Primary
Number of Participants With Serious Treatment-emergent Adverse Events
A serious adverse event (SAE) was any untoward medical occurrence that at any dose was resulting in death, was lifethreatening, requires hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity. SAEs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as serious treatment-emergent AEs (TESAEs). Drug-related TESAEs were TESAEs that had reasonable causal relationship to the study treatment decided by the investigators.
Time frame: After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days
Population: Safety analysis set (SAF): all participants with at least one intake of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BAY1093884 100mg | Number of Participants With Serious Treatment-emergent Adverse Events | TESAEs | 1 Participants |
| BAY1093884 100mg | Number of Participants With Serious Treatment-emergent Adverse Events | Drug-related TESAEs | 0 Participants |
| BAY1093884 225mg | Number of Participants With Serious Treatment-emergent Adverse Events | TESAEs | 2 Participants |
| BAY1093884 225mg | Number of Participants With Serious Treatment-emergent Adverse Events | Drug-related TESAEs | 2 Participants |
| BAY1093884 400mg | Number of Participants With Serious Treatment-emergent Adverse Events | TESAEs | 1 Participants |
| BAY1093884 400mg | Number of Participants With Serious Treatment-emergent Adverse Events | Drug-related TESAEs | 1 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events of Special Interest
Any thromboembolic or thrombotic microangiopathic event or any hypersensitivity reaction was an adverse event of special interest (AESI). AESIs occurring after the first administration of study drug and up to and including 30 days after the last administration of study drug were defined as treatment-emergent AESIs.
Time frame: After the first administration of study drug and up to and including 30 days after the last administration of study drug, with an average of 183 days
Population: Safety analysis set (SAF): all participants with at least one intake of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BAY1093884 100mg | Number of Participants With Treatment-emergent Adverse Events of Special Interest | 0 Participants |
| BAY1093884 225mg | Number of Participants With Treatment-emergent Adverse Events of Special Interest | 2 Participants |
| BAY1093884 400mg | Number of Participants With Treatment-emergent Adverse Events of Special Interest | 1 Participants |