E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hemophilia A or B with inhibitors |
|
E.1.1.1 | Medical condition in easily understood language |
Hemophilia A or B with inhibitors |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060612 |
E.1.2 | Term | Hemophilia A |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060614 |
E.1.2 | Term | Hemophilia B (Factor IX) |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate tolerability and safety of FEIBA reconstituted in a 50% reduced volume of sterile water for injection (SWFI) administered at the standard infusion rate of 2 U/kg/min and at increased rates of 4 and 10 U/kg/min, based on the occurrence of any adverse event, in particular of thromboembolic events and hypersensitivity reactions |
|
E.2.2 | Secondary objectives of the trial |
Exploratory Objectives
1. To monitor pre (within 60 min before the infusion) and post-infusion (at 30 min,
hours 1, 2, 6, 8 and 12) activity of coagulation factor II
2. Evaluate subject treatment preference using Treatment Satisfaction Questionnaire
for Medication (TSQM) and patient preference questionnaire |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥ 18 to ≤ 65 years old at the time of screening
2. Hemophilia A or B of any severity, with a documented ≥ 3 months history of inhibitors (≥ 0.6 BU) requiring the use of bypassing agents (FEIBA or rFVIIa) prior to screening. Inhibitor level will be tested at screening if no documented history is available.
3. Hepatitis C virus (HCV) negative, either by antibody testing or polymerase chain reaction (PCR); or HCV positive with stable liver disease
4. Human immune deficiency virus (HIV) negative; or HIV positive with stable disease and CD4 count ≥ 200 cell/mm3 at screening
5. Adequate venous access
6. Willing and able to comply with the requirements of the protocol
7. If a female of childbearing potential, must have a negative blood pregnancy test and agrees to employ adequate birth control measures for the
duration of the study, such as:
a. Abstain from sexual intercourse
b. Use a reliable method of contraception (contraception such as an intrauterine device, barrier method [e.g., diaphragm or sponge; female condom not permitted] with spermicide, oral contraceptive, injectable progesterone, sub dermal implant), and have their male partner use a condom
8. If female of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:
a. Postmenopausal, defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and with follicle-stimulating hormone levels within the laboratory-defined postmenopausal range or postmenopausal with amenorrhea for at least 24 months and on
hormonal replacement therapy
b. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, bilateral tubal ligation (with no subsequent
pregnancy at least 1 year from bilateral tubal ligation), or bilateral salpingectomy |
|
E.4 | Principal exclusion criteria |
1. Known hypersensitivity to FEIBA or any of its components
2. Advanced liver disease (e.g., liver biopsy confirmed diagnosis of cirrhosis, portal vein hypertension, ascites, prothrombin time [PT] 5 seconds above upper limit of
normal)
3. Planned elective surgery during participation in this study (excluding minor procedures that will not need preventative bleeding treatments, such as exchanges of peripherally inserted central catheters)
4. Platelet count < 100,000/μL
5. Taking Emicizumab (Hemlibra) for bleed prevention
6. Clinical or laboratory evidence of disseminated intravascular coagulation based on medical history
7. Prior history or evidence of thromboembolic event: acute myocardial infarction, deep vein thrombosis, pulmonary embolism, etc.
8. Diagnosis of advanced atherosclerosis, malignancy, and/or other diseases that may increase the subject’s risk of thromboembolic complications
9. Taking any immunomodulating drug (e.g., corticosteroid agents at a dose equivalent to hydrocortisone > 10 mg/day, or α-interferon) within 30 days prior to enrollment except anti-retroviral chemotherapy.
10. Herbal supplements that contain anti-platelet activity
11. Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
12. Family member or employee of the investigator
13. Clinically significant medical, psychiatric or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primaty outcome: Tolerability and safety (local and general) related to infusion rate and volume of reconstitution will be assessed by the occurrence of all AEs including hypersensitivity,
thromboembolic events and infusion site reactions, AEs leading to discontinuation, changes in vital signs and laboratory parameters which are considered AEs. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary objective of the study is to monitor safety parameters throughout the study with a special emphasis on hypersensitivity and thromboembolic events. Adverse event data will be collected at each visit
See protocol for more details. |
|
E.5.2 | Secondary end point(s) |
Exploratory Outcome Measure(s)
1. To monitor pre (within 60 min before the infusion) and post-infusion (at 30 min, hours 1, 2, 6, 8 and 12) activity of coagulation factor II.
2. Evaluate subject treatment preference using Treatment Satisfaction Questionnaire or Medication (TSQM) and patient preference questionnaire
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Coagulation factor II monitoring pre (within 60 min before the infusion) and post-infusion (at 30 min, hours 1, 2, 6, 8 and 12)
2. Questionnaires will be administered 5 times during the study.
See protocol for details. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Part 1: subjects are administered 2 different volumes of FEIBA in a randomized crossover manner. |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Croatia |
Poland |
Romania |
Serbia |
South Africa |
Turkey |
Ukraine |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |