Hemophilia APhase 3Leopold IINCT01233258
A Trial to Compare Prophylaxis Therapy to On-demand Therapy With a New Full Length Recombinant FVIII in Patients With Severe Hemophilia A
A Phase 3 study testing rFVIII (BAY81-8973) on demand, rFVIII (BAY81-8973) prophylaxis low-dose and rFVIII (BAY81-8973) prophylaxis high-dose in people with Hemophilia A, run by Bayer at 47 sites in 18 countries.
Trial summary
The objective of the trial is to demonstrate that 2-3 times per week prophylaxis therapy with BAY81-8973 is superior to on-demand therapy with BAY81-8973 in patients with severe Hemophilia A. The hypothesis is that prophylaxis will result in fewer bleeds than on-demand treatment. Read more about this study
- Who is it for?
- Ages 12 to 65 years, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- rFVIII (BAY81-8973) on demand, rFVIII (BAY81-8973) prophylaxis low-dose and rFVIII (BAY81-8973) prophylaxis high-dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 47 sitesin 18 countries
- Study dates
- Jan 2011to Dec 2012
- 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 65 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male, aged 12 to 65 years
- Severe hemophilia A
- History of more than 150 exposure days (ED) with clotting factor concentrates
- Currently receiving episodic treatment with FVIII; no regular prophylaxis for more than 6 consecutive months in the past 5 years
- No current Factor VIII inhibitor or history of inhibitor
- Willing to use electronic patient diary
Who cannot join
- Presence of another bleeding disease that is different from hemophilia A
- Thrombocytopenia
- Abnormal renal function
- Presence of active liver disease
- Known hypersensitivity to FVIII
Trial locations and contacts
47 sites in 18 countries.
47 sites in 18 countries
China5 sites
Study site
Beijing, 100730
Study site
Guangzhou, Guangdong, 510515
Study site
Shanghai, 200025
Study site
Suzhou, Jiangsu, 215006
Study site
Tianjin, 300020
Japan5 sites
Study site
Hiroshima, Hiroshima, 734-8551
Study site
Kashihara, Nara, 634-8522
Study site
Nishinomiya, Hyōgo, 663-8501
Study site
Shinjuku-ku, Tokyo, 160-0023
Study site
Suginami, Tokyo, 167-0035
Romania4 sites
Study site
Baia Mare, 430031
Study site
Bucharest, 011026
Study site
Bucharest, 022328
Study site
Timișoara, Timiș County, 300011
Russia4 sites
Study site
Barnaul, 656050
Study site
Khabarovsk, 680009
Study site
Saint Petersburg, 191186
Study site
Yekaterinburg, 620149
Serbia4 sites
Study site
Belgrade, 11000
Study site
Kragujevac, 34000
Study site
Niš, 18000
Study site
Novi Sad, 21000
Argentina3 sites
Study site
Buenos Aires, Ciudad Auton. de Buenos Aires, C1221ADC
Study site
Corrientes, Corrientes Province, W3410AVV
Study site
Rosario, Santa Fe Province, S2000CKF
Turkey (Türkiye)3 sites
Study site
Adana, 01330
Study site
Antalya, 07059
Study site
Izmir, 35-100
Ukraine3 sites
Study site
Kiev
Study site
Lviv, 79044
Study site
Simferopol, 95023
United States2 sites
Study site
Dayton, Ohio, 45404
Study site
Houston, Texas, 77030
Colombia2 sites
Study site
Bogotá, Bogota D.C.
Study site
Bucaramanga, Santander Department
Mexico2 sites
Study site
Guadalajara, Jalisco, 44280
Study site
San Luis Potosí City, San Luis Potosí, 78200
South Africa2 sites
Study site
Johannesburg, Gauteng, 2193
Study site
Pretoria, Gauteng, 0001
Thailand2 sites
Study site
Bangkok, Thailand, 10400
Study site
Bangkok, Thailand, 10700
About this study
Official title: A Phase II/III, Randomized, Cross-over, Open-label Trial to Demonstrate Superiority of Prophylaxis Over On-demand Therapy in Previously Treated Subjects With Severe Hemophilia A Treated With Plasma Protein-free Recombinant FVIII Formulated With Sucrose (BAY 81-8973)
The objective of the trial is to demonstrate that 2-3 times per week prophylaxis therapy with BAY81-8973 is superior to on-demand therapy with BAY81-8973 in patients with severe Hemophilia A. The hypothesis is that prophylaxis will result in fewer bleeds than on-demand treatment.
- Conditions
- Hemophilia A
- Being tested
- rFVIII (BAY81-8973) on demand, rFVIII (BAY81-8973) prophylaxis low-dose, rFVIII (BAY81-8973) prophylaxis high-dose
- Keywords
- Haemophilia treatment, rFVIII
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rFVIII (BAY81-8973) on demandBiological
Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization
rFVIII (BAY81-8973) prophylaxis low-doseBiological
Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization.
rFVIII (BAY81-8973) prophylaxis high-doseBiological
Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: rFVIII on demand first CS/EP then CS/ADJ | Experimental | Participants received on-demand treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months, followed by cross-over to study drug assayed by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months. Receives: Biological: rFVIII (BAY81-8973) on demand |
| Arm 2: rFVIII on demand first CS/ADJ then CS/EP | Experimental | Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/ADJ for 6 months, followed by cross-over to study drug assayed by CS/EP for 6 months. Receives: Biological: rFVIII (BAY81-8973) on demand |
| Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ | Experimental | Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII(BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months. Receives: Biological: rFVIII (BAY81-8973) prophylaxis low-dose |
| Arm 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP | Experimental | Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months. Receives: Biological: rFVIII (BAY81-8973) prophylaxis low-dose |
| Arm 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ | Experimental | Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months. Receives: Biological: rFVIII (BAY81-8973) prophylaxis high-dose |
| Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/EP | Experimental | Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII(BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months. Receives: Biological: rFVIII (BAY81-8973) prophylaxis high-dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Number of All Bleeds
The annualized number of bleeds experienced by participants
Measured: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)
Secondary outcomes (3)
Annualized Number of All Bleeds During CS/EP Period
The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/EP
Measured: Up to 6 months (6 months on CS/EP potency assignment)
Annualized Number of All Bleeds During CS/ADJ Period
The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/ADJ
Measured: Up to 6 months (6 months on CS/ADJ potency assignment)
Percentage of Bleeds Per Participant Controlled With ≤ 2 Injections in Participants Treated on Demand With rFVIII (BAY81-8973)
The percentage of bleeds per participant on on-demand treatment that stopped after two or fewer injections
Measured: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2010 (estimated)
- Study startJan 2011
- Primary completionDec 2012
- Study completionDec 2012
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 (3)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by BayerThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01233258
- Sponsor's protocol ID
- 14319
- Other IDs
- 2009-012150-20, 2009
- Acronym
- Leopold II
- Status last verified
- Oct 2016
- First submitted
- 2 Nov 2010
- Last updated
- 28 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kitchen S, Katterle Y, Beckmann H, Maas Enriquez M. Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples. J Thromb Haemost. 2016 Jun;14(6):1192-9. doi: 10.1111/jth.13322. Epub 2016 May 3.
PubMed 27002680Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.
PubMed 26931631Kavakli K, Yang R, Rusen L, Beckmann H, Tseneklidou-Stoeter D, Maas Enriquez M; LEOPOLD II Study Investigators. Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II). J Thromb Haemost. 2015 Mar;13(3):360-9. doi: 10.1111/jth.12828.
PubMed 25546368
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III, Randomized, Cross-over, Open-label Trial to Demonstrate Superiority of Prophylaxis Over On-demand Therapy in Previously Treated Subjects With Severe Hemophilia A Treated With Plasma Protein-free Recombinant FVIII Formulated With Sucrose (BAY 81-8973)
- ClinicalTrials.gov ID
- NCT01233258
- Acronym / sponsor ID
- Leopold II / 14319
- Conditions
- Hemophilia A
- Keywords
- Haemophilia treatment, rFVIII
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- Jan 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 3 Nov 2010 (estimated)
- Results
- Posted 11 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the trial is to demonstrate that 2-3 times per week prophylaxis therapy with BAY81-8973 is superior to on-demand therapy with BAY81-8973 in patients with severe Hemophilia A. The hypothesis is that prophylaxis will result in fewer bleeds than on-demand treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm 1: rFVIII on demand first CS/EP then CS/ADJ | Experimental | Biological: rFVIII (BAY81-8973) on demandParticipants received on-demand treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months, followed by cross-over to study drug assayed by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months. |
| Arm 2: rFVIII on demand first CS/ADJ then CS/EP | Experimental | Biological: rFVIII (BAY81-8973) on demandParticipants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/ADJ for 6 months, followed by cross-over to study drug assayed by CS/EP for 6 months. |
| Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ | Experimental | Biological: rFVIII (BAY81-8973) prophylaxis low-doseParticipants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII(BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months. |
| Arm 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP | Experimental | Biological: rFVIII (BAY81-8973) prophylaxis low-doseParticipants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months. |
| Arm 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ | Experimental | Biological: rFVIII (BAY81-8973) prophylaxis high-doseParticipants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months. |
| Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/EP | Experimental | Biological: rFVIII (BAY81-8973) prophylaxis high-doseParticipants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII(BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Male, aged 12 to 65 years
- Severe hemophilia A
- History of more than 150 exposure days (ED) with clotting factor concentrates
- Currently receiving episodic treatment with FVIII; no regular prophylaxis for more than 6 consecutive months in the past 5 years
- No current Factor VIII inhibitor or history of inhibitor
Key exclusion criteria (5 listed)
- Presence of another bleeding disease that is different from hemophilia A
- Thrombocytopenia
- Abnormal renal function
- Presence of active liver disease
- Known hypersensitivity to FVIII
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 |
|---|---|---|
| rFVIII (BAY81-8973) on demandParticipants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization | Biological | Arm 1: rFVIII on demand first CS/EP then CS/ADJ, Arm 2: rFVIII on demand first CS/ADJ then CS/EP |
| rFVIII (BAY81-8973) prophylaxis low-doseParticipants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization. | Biological | Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ, Arm 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP |
| rFVIII (BAY81-8973) prophylaxis high-doseParticipants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization. | Biological | Arm 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ, Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/EP |
Primary outcome
Annualized Number of All Bleeds
Time frame: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)
The annualized number of bleeds experienced by participants
3 secondary outcomes
Annualized Number of All Bleeds During CS/EP Period
Time frame: Up to 6 months (6 months on CS/EP potency assignment)
Annualized Number of All Bleeds During CS/ADJ Period
Time frame: Up to 6 months (6 months on CS/ADJ potency assignment)
Percentage of Bleeds Per Participant Controlled With ≤ 2 Injections in Participants Treated on Demand With rFVIII (BAY81-8973)
Time frame: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27002680Kitchen S, Katterle Y, Beckmann H, Maas Enriquez M. Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples. J Thromb Haemost. 2016 Jun;14(6):1192-9. doi: 10.1111/jth.13322. Epub 2016 May 3.
- Results publication: PubMed 26931631Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.
- Derived from this study: PubMed 25546368Kavakli K, Yang R, Rusen L, Beckmann H, Tseneklidou-Stoeter D, Maas Enriquez M; LEOPOLD II Study Investigators. Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II). J Thromb Haemost. 2015 Mar;13(3):360-9. doi: 10.1111/jth.12828.
- Click here to find information about studies related to Bayer Healthcare products conducted in EuropeLink provided by the sponsor.
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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.
Bayer Study Director study director
Bayer
47 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rFVIII (BAY81-8973) on demand, rFVIII (BAY81-8973) prophylaxis low-dose and rFVIII (BAY81-8973) prophylaxis high-dose in people with Hemophilia A, run by Bayer at 47 sites in 18 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 6 inclusion and 5 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 28 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in China, Japan, Romania, Russia, Serbia and 13 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 11 Feb 2014). 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 All Bleeds (time frame: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)). 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 NCT01233258, which also lists 3 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 28 Nov 2016.