Severe Haemophilia APhase 3NCT01863758
Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Patients With Severe Haemophilia A
A Phase 3 study testing Human-cl rhFVIII in people with Severe Haemophilia A, run by Octapharma at 20 sites in 8 countries.
Trial summary
To compare the number of breakthrough bleeds under tailored prophylaxis with Human cell line recombinant factor FVIII (Human-cl rhFVIII) with the historical bleeding rate from patients who received Human-cl rhFVIII as on demand treatment. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Severe Haemophilia A
- What is being tested?
- Human-cl rhFVIII
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 20 sitesin 8 countries
- Study dates
- Aug 2013to Jan 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 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Severe haemophilia A (FVIII:C < 1%) according to medical history.
- Male patients ≥ 18 years old.
- Previous treatment with a FVIII concentrate (regular prophylaxis with good compliance or on-demand treatment) for at least 150 exposure days (EDs).
- Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start.
- Immunocompetence (CD4+ count > 200/microliter).
- HIV-negative, if positive, viral load < 200 particles/microliter or < 400,000 copies/mL.
- Freely given written informed consent
Who cannot join
- Any coagulation disorder other than haemophilia A.
- Present or past FVIII inhibitor activity (> 0.6 Bethesda Unit [BU])
- Severe liver or kidney disease.
Trial locations and contacts
20 sites in 8 countries.
20 sites in 8 countries
Poland4 sites
University Teaching Hospital in Bialystok, Teaching Department of Hematology with a Subdepartment of Vascular Diseases
Bialystok
University Clinical Center, Teaching Department of Hematology and Transplantology
Gdansk
Nicolaus Copernicus Municipal Specialist Hospital, Department of Hematology
Torun
Institute of Hematology and Transfusion Medicine, Depart. of Hemostatic Disorders and Internal Diseases
Warsaw
United Kingdom4 sites
Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
Basingstoke
Royal London Hospital, Barts and the London Hemophilia Center
London
Manchester Royal Infirmary, Department of Clinical Hematology
Manchester
Royal Hallamshire Hospital
Sheffield
Bulgaria3 sites
University Multiprofile Hospital for Active Treatment
Plovdiv
Specialized Hospital for Active Treatment
Sofia
Multiprofile Hospital for Active Treatment
Varna
Germany2 sites
Vivantes Hospital in Friedrichshain
Berlin
SRH Kurpfalzklinik Heidelberg GMBH
Heidelberg
Hungary2 sites
Hungarian National Healthcare Center
Budapest
University of Debrecen, Medical and Health Science Center
Debrecen
Romania2 sites
Sanador SRL
Bucharest
Louis Turcanu Emergency Clinical Children's Hospital
Timișoara
Slovakia2 sites
University Hospital Saint Cyril and Metod
Bratislava
University Hospital Martin, Department of Hematology and Transfusiology
Martin
About this study
Official title: Prospective, Open-label, Multicenter Phase 3b Study to Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A
To compare the number of breakthrough bleeds under tailored prophylaxis with Human cell line recombinant factor FVIII (Human-cl rhFVIII) with the historical bleeding rate from patients who received Human-cl rhFVIII as on demand treatment.
Read the detailed description
There were 3 phases in this study: (1) An initial pharmacokinetic (PK) assessment in which participants received a single infusion of 60±5 IU/kg of Human-cl rhFVIII; blood samples were collected for 72 hours following the infusion. (2) Prophylactic Treatment-Phase I during which participants received infusions of 30-40 IU/kg of human-cl rhFVIII every other day or 3x/week for 1-3 months. (3) Prophylactic Treatment-Phase II during which the dose and dosing interval were determined individually from data gathered in the initial PK assessment. The maximum dosing interval with a dose of ≤ 60-80 IU/kg that maintains a trough level of ≥ 0.01 IU/mL was determined. Participants were treated for 6 months.
- Conditions
- Severe Haemophilia A
- Being tested
- Human-cl rhFVIII
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human-cl rhFVIIIBiological
Human-cl rhFVIII was provided as a freeze-dried concentrate to be reconstituted in water for injection.
| Study group | Role | What they receive |
|---|---|---|
| Human-cl rhFVIII | Experimental | Up to 60-80 IU/kg of intravenous Human-cl rhFVIII was administered at an individually determined dose and dose interval. Receives: Biological: Human-cl rhFVIII |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Number of Bleeding Episodes (BE) in Phase II
The annualized number of total BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as any BE whether treated or not during Phase II of the study; BEs related to surgery were not included. This study was considered as showing efficacy if the annualized number of BEs was reduced by 50% compared to the number of BEs observed in study GENA-01 where patient where severe Hemophilia A patients were treated on-demand (NCT00989196).
Measured: Beginning to the end of Phase II (6 months)
Secondary outcomes (4)
Annualized Number of Spontaneous Bleeding Episodes (BE) in Phase II
The annualized number of spontaneous BEs was calculated for each participant as follows: d*y/t, where y = the number of spontaneous BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A spontaneous bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery and BEs due to trauma or due to other causes were not included.
Measured: Beginning to the end of Phase II (6 months)
Annualized Number of Bleeding Episodes (BE) in Phase II in Participants With ≤ 2 Treatments/Week
The annualized number of BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery were not included.
Measured: Beginning to the end of Phase II (6 months)
Median Dosing Interval During Individually Tailored Prophylaxis
The median time between 2 prophylactic doses of Human-cl rhFVIII in the prophylactic treatment phase II were determined per patient
Measured: Beginning to the end of Phase II (6 months)
Dosage Per Week in Phase II
The mean dosage per week during Phase II of the study are reported.
Measured: Beginning to the end of Phase II (6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2013 (estimated)
- Study startAug 2013
- Primary completionJan 2015
- Study completionJan 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.
- Other trials for Severe Haemophilia AStudies of the same condition, open and under way.
- More trials run by OctapharmaThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Octapharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01863758
- Sponsor's protocol ID
- GENA-21
- Status last verified
- Jul 2017
- First submitted
- 23 May 2013
- Last updated
- 30 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Open-label, Multicenter Phase 3b Study to Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A
- ClinicalTrials.gov ID
- NCT01863758
- Acronym / sponsor ID
- GENA-21
- Conditions
- Severe Haemophilia A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- OctapharmaIndustry (pharma, biotech, devices)
- Study start
- Aug 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 29 May 2013 (estimated)
- Results
- Posted 30 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare the number of breakthrough bleeds under tailored prophylaxis with Human cell line recombinant factor FVIII (Human-cl rhFVIII) with the historical bleeding rate from patients who received Human-cl rhFVIII as on demand treatment.
Detailed description
There were 3 phases in this study: (1) An initial pharmacokinetic (PK) assessment in which participants received a single infusion of 60±5 IU/kg of Human-cl rhFVIII; blood samples were collected for 72 hours following the infusion. (2) Prophylactic Treatment-Phase I during which participants received infusions of 30-40 IU/kg of human-cl rhFVIII every other day or 3x/week for 1-3 months. (3) Prophylactic Treatment-Phase II during which the dose and dosing interval were determined individually from data gathered in the initial PK assessment. The maximum dosing interval with a dose of ≤ 60-80 IU/kg that maintains a trough level of ≥ 0.01 IU/mL was determined. Participants were treated for 6 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Human-cl rhFVIII | Experimental | Biological: Human-cl rhFVIIIUp to 60-80 IU/kg of intravenous Human-cl rhFVIII was administered at an individually determined dose and dose interval. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Severe haemophilia A (FVIII:C < 1%) according to medical history.
- Male patients ≥ 18 years old.
- Previous treatment with a FVIII concentrate (regular prophylaxis with good compliance or on-demand treatment) for at least 150 exposure days (EDs).
- Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start.
- Immunocompetence (CD4+ count > 200/microliter).
Key exclusion criteria (3 listed)
- Any coagulation disorder other than haemophilia A.
- Present or past FVIII inhibitor activity (> 0.6 Bethesda Unit [BU])
- Severe liver or kidney disease.
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 |
|---|---|---|
| Human-cl rhFVIIIHuman-cl rhFVIII was provided as a freeze-dried concentrate to be reconstituted in water for injection. | Biological | Human-cl rhFVIII |
Primary outcome
Annualized Number of Bleeding Episodes (BE) in Phase II
Time frame: Beginning to the end of Phase II (6 months)
The annualized number of total BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as any BE whether treated or not during Phase II of the study; BEs related to surgery were not included. This study was considered as showing efficacy if the annualized number of BEs was reduced by 50% compared to the number of BEs observed in study GENA-01 where patient where severe Hemophilia A patients were treated on-demand (NCT00989196).
4 secondary outcomes
Annualized Number of Spontaneous Bleeding Episodes (BE) in Phase II
Time frame: Beginning to the end of Phase II (6 months)
Annualized Number of Bleeding Episodes (BE) in Phase II in Participants With ≤ 2 Treatments/Week
Time frame: Beginning to the end of Phase II (6 months)
Median Dosing Interval During Individually Tailored Prophylaxis
Time frame: Beginning to the end of Phase II (6 months)
Dosage Per Week in Phase II
Time frame: Beginning to the end of Phase II (6 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Human-cl rhFVIII in people with Severe Haemophilia A, run by Octapharma at 20 sites in 8 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 7 inclusion and 3 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 30 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Poland, United Kingdom, Bulgaria, Germany, Hungary and 3 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 30 Jan 2018). 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?
Annualized Number of Bleeding Episodes (BE) in Phase II (time frame: Beginning to the end of Phase II (6 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jan 2018; AzTrials last refreshed its copy on 8 Nov 2026.