Overview
This study is evaluating an investigational drug, eptacog beta (EB), for the treatment and prevention of acute bleeding episodes in people with Glanzmann Thrombasthenia, a rare inherited bleeding disorder. Eptacog beta (EB) is not currently approved by the U.S. Food and Drug Administration (FDA) for this condition.
The study will assess the effectiveness and safety of eptacog beta (EB) when used to treat serious bleeding events, and in an optional phase, when used routinely to prevent bleeding. During the first three (3) months, participants will manage any bleeding episodes with their standard treatment (e.g., factor products or platelet transfusions). After this initial period, they will use the study drug to treat serious bleeding events.
Participants will have approximately 4 to 5 visits with their hematologist over the 9-month study period. They will also be asked to complete a diary documenting bleeding episodes and treatments, and to answer questions about how bleeding affects their daily life. Blood samples will be collected to monitor their condition and any potential side effects of the study drug.
At the end of the main study, participants will have the option to enter an optional extension phase, where they will receive routine intravenous infusions of the study drug 2 to 3 times per week for 6 months to help prevent future bleeding episodes and complications.
Description
This study aims to investigate eptacog beta (EB), a new form of recombinant activated factor VIIa, for bleeding management in persons with Glanzmann thrombasthenia regardless of platelet refractoriness status.
Investigators will enroll six (6) people (adult or pediatric) with Glanzmann thrombasthenia (GT) who have a severe bleeding phenotype (defined as ≥ 2 treated bleeding events in the past 12 months, ≥ 1 hospitalization for bleeding or severe anemia or requiring prophylactic therapy to prevent bleeding). Initially, a retrospective chart review will collect data regarding bleeding events and their management over the previous 6 months before enrollment.
The initial 3 months of this trial will be a non-interventional phase during which time, participants will receive standard-of-care on-demand therapy for acute bleeding events at the discretion of their hematologist. They will complete a diary logging their bleeding events and their management. Hemostatic efficacy following acute bleed treatment will be evaluated using a 4-point hemostasis efficacy score.
Following this initial non-interventional phase, participants will use eptacog beta (EB) 75 mcg/kg/dose every 3 Hours for the management of breakthrough bleeding episodes that are not responsive to local hemostatic control and anti-fibrinolytic therapies, with the precise frequency of infusions and duration of treatment at the discretion of the subject's treating physician. This on-demand interventional phase will last 6 months. During this time, participants will log their acute bleeding episodes and management. At varying time points following a dose of EB, participants will complete a 4-point hemostasis scale assessing the efficacy of EB in controlling bleeding.
Following the 6-month interventional on-demand phase, participants may choose to continue in an interventional prophylaxis arm.
Eligibility
Inclusion Criteria:
- Adult or Pediatric persons with inherited Glanzmann thrombasthenia (see diagnostic criteria below)
- Severe bleeding phenotype
- Adequate hepatic function
- Adequate renal function
- Adults subject (≥18 years of age) or caregiver (parent or legally authorized representative) for minor subjects, subjects with cognitive impairment, or subjects with impaired decision-making capacity have provided written informed consent, and the participant has given consent/assent (if applicable)
- Ability to speak, read, and understand the English language
Exclusion Criteria:
- Thrombocytopenia (platelet count \< 100k)
- Acquired Glanzmann thrombasthenia secondary to autoimmune disease, malignancy, or medication
- Inherited or acquired bleeding diathesis other than Glanzmann thrombasthenia
- Have a history of venous or arterial thrombotic event within 2 years of study enrollment
- Active malignancy
- Known or suspected hypersensitivity to rabbits, rabbit protein, other forms of rFVIIa, or to any of the EB excipients
- Have received an investigational drug within 30 days or within 5 half-lives of that investigational drug (whichever is longer) or are expected to receive such a drug during participation in this study
- Be using aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), herbs, natural medications, or other drugs with platelet inhibitor properties for the duration of the study
- Be using or administered anticoagulant agents for the duration of the study
- Have any life-threatening disease or other disease or condition which, according to the investigator's judgement, could imply a potential hazard to the patient, or interfere with the study participation or study outcome
- Use of systemic immunomodulators at enrollment or planned use during the study