Hemophilia A With InhibitorsPhase 3NCT02020369
Phase III Study of Coagulation FVIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors
A Phase 3 study testing Coagulation Factor VIIa (Recombinant) in people with Hemophilia A With Inhibitors and Hemophilia B With Inhibitors, run by rEVO Biologics at 17 sites in 10 countries.
Trial summary
The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX Read more about this study
- Who is it for?
- Ages 12 to 75 years, men only
- Conditions the study is for
- Hemophilia A With Inhibitors, Hemophilia B With Inhibitors
- What is being tested?
- Coagulation Factor VIIa (Recombinant)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 17 sitesin 10 countries
- Study dates
- Apr 2014to Aug 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 75 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- be male with a diagnosis of congenital hemophilia A and/or B of any severity
- have one of the following:
- a positive inhibitor test Bethesda Unit (BU) ≥ 5 (as confirmed at screening by the institutional lab), OR
- a BU<5 but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings, OR
- a BU<5 but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings
- be 12 years or older, up to and including 75 years of age (NOTE: different age restrictions may apply per local regulation and/or ethical considerations)
- have at least 3 bleeding episodes of any severity in the past 6 months be capable of understanding and willing to comply with the conditions of the protocol
- have read, understood and provided written informed consent (patient and/or parent(s)/legal guardian(s) if <18 years of age)
Who cannot join
- have any coagulation disorder other than hemophilia A or B
- be immuno-suppressed (i.e., the patient should not be receiving systemic immunosuppressive medication, cluster of differentiation 4 (CD4) counts at screening should be >200/µl)
- have a known allergy or hypersensitivity to rabbits
- have platelet count <100,000/mL
- have had within one month prior to first administration of the study drug in this study a major surgical procedure (e.g. orthopedic, abdominal)
- have received an investigational drug within 30 days of the first study drug administration, or is expected to receive such drug during participation in this study
Show all 10Show fewer
- have a clinically relevant hepatic (AST and/or alanine aminotransferase (ALT) >3 times the upper limit of normal) and/or renal impairment (creatinine >2 times the upper limit of normal)
- have a history of arterial and/or venous thromboembolic events (such as myocardial infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis or pulmonary embolism) within 2 years prior to first dose of study drug, or current New York Heart Association (NYHA) functional classification score of stage II -IV
- have an active malignancy (those with non-melanoma skin cancer are allowed)
- have any life-threatening disease or other disease or condition which, according to the investigator's judgment, could imply a potential hazard to the patient, interfere with the trial participation or trial outcome (e.g., a history of non-responsiveness to bypassing products).
Trial locations and contacts
17 sites in 10 countries.
17 sites in 10 countries
United States5 sites
University of Colorado Hemophilia and Thrombosis Center
Aurora, Colorado, 80045
Rush University Medical Center
Chicago, Illinois, 60612
Orthopaedic Hemophilia Treatment Center
Los Angeles, California, 90007
University of Minnesota Medical Center Fairview
Minneapolis, Minnesota, 55455
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Russia3 sites
Kirov Research Institute of Hematology and Blood Transfusion
Kirov
Hematology Research Center
Moscow
City Outpatient Clinic #37
Saint Petersburg
Ukraine2 sites
Kyiv City Clinical Hospital #9
Kyiv
Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine
Lviv
Belarus1 site
Republican Research Center for Radiation Medicine and Human Ecology
Homyel
Bulgaria1 site
Specialized Hospital for Active Treatment of Hematological Diseases
Sofia
United Kingdom1 site
Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
Basingstoke
About this study
Official title: A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors to Factor VIII or IX
The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX
Read the detailed description
This was a global, multicenter, Phase III, prospective, open-label, randomized, crossover study. After obtaining informed consent and performance of screening procedures, patients who met all inclusion and exclusion criteria were randomized to one of two treatment regimens as follows:
- 75 µg/kg treatment regimen
- 225 µg/kg treatment regimen
For each treatment regimen there were two phases:
- Phase A (Initial phase)
- Phase B (Treatment phase)
The assigned treatment regimen was the dose administered in Phase A and was the starting dose in Phase B.
- Being tested
- Coagulation Factor VIIa (Recombinant)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coagulation Factor VIIa (Recombinant)Biological
A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX
| Study group | Role | What they receive |
|---|---|---|
| FVIIa: 75 µg/kg first, then 225 µg/kg | Experimental | Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion. Receives: Biological: Coagulation Factor VIIa (Recombinant) |
| FVIIa: 225 µg/kg first, then 75 µg/kg | Experimental | Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion. Receives: Biological: Coagulation Factor VIIa (Recombinant) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Successfully Treated Mild/Moderate Bleeding Episodes
For the primary efficacy endpoint, successful treatment of a bleeding episode was defined as a combination of the following:
- "Good" or "Excellent" response noted by the patient
- Study drug treatment: No further treatment with study drug beyond timepoint for this bleeding episode
- No other hemostatic treatment needed for this bleeding episode
- No administration of blood products that would indicate continuation of bleeding beyond timepoint
- No increase of pain beyond timepoint that could not otherwise be explained
Measured: 12 hours after first administration of study drug
Secondary outcomes (4)
Proportion of Mild/Moderate Bleeding Episodes With Patient (Pt)-Reported "Good" or "Excellent" Responses at 12 Hours
Based on Patient-Reported "Good" or "Excellent" responses as per the below descriptions:
Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug.
Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage). No additional infusion of study drug was required.
Measured: at 12 hours
Time to Assessment of a "Good" or "Excellent" Response of Mild/Moderate Bleeding Episodes by the Patient
Categories of Response to Treatment are Described as Follows:
None: No noticeable effect of the treatment on the bleed or worsening of patient's condition. Continuation of treatment with the study drug was needed.
Moderate: Some effect of the treatment on the bleed was noticed, e.g., pain decreased or bleeding signs improved, but bleed continued and required continued treatment with the study drug. Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug.
Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage). No additional infusion of study drug was required.
Measured: Within 24 hours of Bleeding Episode
Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode
Measured: Within 24 hours of Bleeding Episode
Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode
Measured: Through study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study startApr 2014
- Primary completionJul 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemophilia A With InhibitorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- rEVO Biologics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Laboratoire français de Fractionnement et de Biotechnologies
- Responsible party
- Sponsor
- Investigators
- Jean Francois Schved, MD, Principal investigator, Saint Eloi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02020369
- Sponsor's protocol ID
- RB-FVIIa-006-13
- Status last verified
- May 2017
- First submitted
- 18 Dec 2013
- Last updated
- 14 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Young G, Mahlangu J, Boggio LN, Carcao M, Dargaud Y, Escobar M, Giermasz A, Hermans C, Kuriakose P, Miesbach W, Nance D, Rafique A, Sidonio RF Jr, Vilchevska KV, Wang M, Pipe SW. Treatment of severe bleeds with eptacog beta in hemophilia A or B with inhibitors: a post hoc analysis of the PERSEPT 1 and 2 trials. Blood Vessel Thromb Hemost. 2025 Mar 27;2(3):100069. doi: 10.1016/j.bvth.2025.100069. eCollection 2025 Aug.
PubMed 40765904Carcao M, Hermans C, Giermasz A, Kessler C, Miesbach W, Quon D, Windyga J, Mahlangu J. Safety and Use of Eptacog Beta 225 microg/kg in Patients With Haemophilia A or B With Inhibitors. Haemophilia. 2025 Sep;31(5):957-965. doi: 10.1111/hae.70083. Epub 2025 Jul 17.
PubMed 40674256
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors to Factor VIII or IX
- ClinicalTrials.gov ID
- NCT02020369
- Acronym / sponsor ID
- RB-FVIIa-006-13
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- rEVO BiologicsIndustry (pharma, biotech, devices)
- Collaborators
- Laboratoire français de Fractionnement et de Biotechnologies
- Study start
- Apr 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Posted 14 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX
Detailed description
This was a global, multicenter, Phase III, prospective, open-label, randomized, crossover study. After obtaining informed consent and performance of screening procedures, patients who met all inclusion and exclusion criteria were randomized to one of two treatment regimens as follows:
- 75 µg/kg treatment regimen
- 225 µg/kg treatment regimen
For each treatment regimen there were two phases:
- Phase A (Initial phase)
- Phase B (Treatment phase)
The assigned treatment regimen was the dose administered in Phase A and was the starting dose in Phase B.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FVIIa: 75 µg/kg first, then 225 µg/kg | Experimental | Biological: Coagulation Factor VIIa (Recombinant)Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion. |
| FVIIa: 225 µg/kg first, then 75 µg/kg | Experimental | Biological: Coagulation Factor VIIa (Recombinant)Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion. |
Who may qualify
- Ages
- 12 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- be male with a diagnosis of congenital hemophilia A and/or B of any severity
- have one of the following:
- a positive inhibitor test Bethesda Unit (BU) ≥ 5 (as confirmed at screening by the institutional lab), OR
- a BU<5 but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings, OR
- a BU<5 but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings
Key exclusion criteria (10 listed)
- have any coagulation disorder other than hemophilia A or B
- be immuno-suppressed (i.e., the patient should not be receiving systemic immunosuppressive medication, cluster of differentiation 4 (CD4) counts at screening should be >200/µl)
- have a known allergy or hypersensitivity to rabbits
- have platelet count <100,000/mL
- have had within one month prior to first administration of the study drug in this study a major surgical procedure (e.g. orthopedic, abdominal)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Coagulation Factor VIIa (Recombinant)A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX | Biological | FVIIa: 225 µg/kg first, then 75 µg/kg, FVIIa: 75 µg/kg first, then 225 µg/kg |
Primary outcome
Proportion of Successfully Treated Mild/Moderate Bleeding Episodes
Time frame: 12 hours after first administration of study drug
For the primary efficacy endpoint, successful treatment of a bleeding episode was defined as a combination of the following: * "Good" or "Excellent" response noted by the patient * Study drug treatment: No further treatment with study drug beyond timepoint for this bleeding episode * No other hemostatic treatment needed for this bleeding episode * No administration of blood products that would indicate continuation of bleeding beyond timepoint * No increase of pain beyond timepoint that could not otherwise be explained
4 secondary outcomes
Proportion of Mild/Moderate Bleeding Episodes With Patient (Pt)-Reported "Good" or "Excellent" Responses at 12 Hours
Time frame: at 12 hours
Time to Assessment of a "Good" or "Excellent" Response of Mild/Moderate Bleeding Episodes by the Patient
Time frame: Within 24 hours of Bleeding Episode
Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode
Time frame: Within 24 hours of Bleeding Episode
Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode
Time frame: Through study completion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40765904Young G, Mahlangu J, Boggio LN, Carcao M, Dargaud Y, Escobar M, Giermasz A, Hermans C, Kuriakose P, Miesbach W, Nance D, Rafique A, Sidonio RF Jr, Vilchevska KV, Wang M, Pipe SW. Treatment of severe bleeds with eptacog beta in hemophilia A or B with inhibitors: a post hoc analysis of the PERSEPT 1 and 2 trials. Blood Vessel Thromb Hemost. 2025 Mar 27;2(3):100069. doi: 10.1016/j.bvth.2025.100069. eCollection 2025 Aug.
- Derived from this study: PubMed 40674256Carcao M, Hermans C, Giermasz A, Kessler C, Miesbach W, Quon D, Windyga J, Mahlangu J. Safety and Use of Eptacog Beta 225 microg/kg in Patients With Haemophilia A or B With Inhibitors. Haemophilia. 2025 Sep;31(5):957-965. doi: 10.1111/hae.70083. Epub 2025 Jul 17.
- Individual participant dataSharing planned: No
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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.
Jean Francois Schved, MD principal investigator
Saint Eloi Hospital
17 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Coagulation Factor VIIa (Recombinant) in people with Hemophilia A With Inhibitors and Hemophilia B With Inhibitors, run by rEVO Biologics at 17 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Russia, Ukraine, Belarus, Bulgaria and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Successfully Treated Mild/Moderate Bleeding Episodes (time frame: 12 hours after first administration of study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02020369, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2017.