Hemophilia APhase 3SPINARTNCT00623480
Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects Compared to That of Episodic Treatment
A Phase 3 study testing Recombinant Factor VIII (Kogenate FS, BAY14-2222) in people with Hemophilia A, run by Bayer at 38 sites in 4 countries.
Trial summary
To evaluate the effect of secondary prophylaxis as compared to episodic treatment on bleeding frequency (number of bleeds per year) and on joint damage. Read more about this study
- Who is it for?
- Ages 12 to 50 years, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Recombinant Factor VIII (Kogenate FS, BAY14-2222)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 38 sitesin 4 countries
- Study dates
- Mar 2008to Nov 2013
- 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 50 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Males aged 12 to 50 years (US and Argentina)
- Males aged 18 to 50 years (other countries)
- Subjects with severe hemophilia A (<1% FVIII:C) as confirmed by the central lab from a sample obtained at least 96 hours after FVIII administration wash-out. Allow for the inclusion of a maximum of 10% (n=8) of patients with 1-2% FVIII:C baseline levels as long as they exhibit clinical severity and comply with all other inclusion criteria.
- Subjects with at least 150 prior exposure days with any FVIII
- Subjects who have been on episodic treatment and no known regular prophylaxis treatment for more than 12 consecutive months in the previous 5 years
- Subjects with 6 to 24 bleeding events and/or treatments in the previous 6 months prior to study entry which are documented and available in the subjects medical records. Documentation can include records from previous physicians, specific home treatment records, emergency room or hospital records, x-ray reports, etc. The investigator can also document with a detailed note the number of bleeds reported by the subject in the last 6 months.
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- Subjects with inhibitor formation surveillance (inhibitor or recovery testing) over the ten years prior to enrollment documented by the investigator and who do not have a history of any of the following:
- A positive inhibitor titer of 5.0 Bethesda Unit (BU) or greater by either BU assay system at any time since first exposure to exogenous factor VIII
- A positive inhibitor test result of 1.0 or greater performed by the original BU assay at any time in the past 10 years (A subject can have more than one positive inhibitor test of 0.6 or greater by the original BU assay test but all must be less than 1.0 BU using the original BU assay.)
- A positive inhibitor test result of 0.6 or greater performed by the Nijmegen method at any time in the past 10 years
- Subjects with no inhibitor activity by Nijmegen-modified Bethesda assay, either positive (> 0.6 BU is considered positive) or borderline (> 0.3 and < 0.6 BU is considered borderline) as measured in the current study reference laboratory
Who cannot join
- Subjects with any other bleeding disease besides hemophilia A (i.e. von Willebrand disease)
- Subjects with thrombocytopenia (platelets < 100,000/mm3)
- Subjects with abnormal renal function (Cockcroft-Gault Creatinine Clearance value of 60 mL/min or lower)
- Subjects with active hepatic disease (Aspartate aminotransferase [AST] or Alanine aminotransferase [ALT] > 5xUpper Limit of Normal (ULN))
- Subjects on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study (the following drugs are however allowed: interferon-a treatment for Hepatitis C virus (HCV), Highly active anti-retroviral therapy (HAART) therapy for human immunodeficiency virus (HIV) and/or a total of two courses of pulse treatment with steroids for a maximum of 7 days at 1mg/kg or less)
- Subjects with an absolute CD4 lymphocyte cell count < 200 cells/mm3 (due to HIV, HCV or another suspected medical condition)
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- Subjects with known hypersensitivity to rFVIII, mouse or hamster proteins
- Subjects who are receiving or had received other experimental drugs within 1 month prior to study entry
- Subjects who require any pre-medication to tolerate FVIII injections (e.g. anti-histamines)
- Subjects who are unwilling to comply with study visits or either of the possible treatment regimens
- Subjects who have a planned orthopedic intervention to be performed during the study that may substantially affect bleeding (e.g. surgical or chemical or radiological synovectomy)
- Subjects who are not suitable for participation in this study for any reason, according to the Investigator
- Subjects who have poor joint status as defined by routine need for a wheelchair or unable to ambulate without the assistance of a brace, cane or crutches
- Three or more joints that are already fused or "frozen" also called ankylosis
Trial locations and contacts
38 sites in 4 countries.
38 sites in 4 countries
United States28 sites
Study site
Atlanta, Georgia, 30322
Study site
Aurora, Colorado, 80045
Study site
Boston, Massachusetts, 02115
Study site
Chicago, Illinois, 60611
Study site
Chicago, Illinois, 60612
Study site
Cleveland, Ohio, 44106
Study site
Detroit, Michigan, 48201-2196
Study site
Hershey, Pennsylvania, 17033-0850
Study site
Houston, Texas, 77030
Study site
Indianapolis, Indiana, 46260
Study site
Iowa City, Iowa, 52242-1089
Study site
Kansas City, Missouri, 64108
Study site
Knoxville, Tennessee, 37920
Study site
Las Vegas, Nevada, 89109-2803
Study site
Little Rock, Arkansas, 72202
Study site
Louisville, Kentucky, 40202
Study site
Milwaukee, Wisconsin, 53226
Study site
Minneapolis, Minnesota, 55455
Study site
New York, New York, 10029
Study site
New York, New York, 10065
Study site
Newark, New Jersey, 07112
Study site
Orange, California, 92868
Study site
Orlando, Florida, 32801
Study site
Pittsburgh, Pennsylvania, 15213
Study site
Sacramento, California, 95817
Study site
Salt Lake City, Utah, 84132
Study site
Tucson, Arizona, 85724
Study site
Washington D.C., District of Columbia, 20007-2197
Romania5 sites
Study site
Brasov, 50035
Study site
Bucharest, 022328
Study site
Bucharest, 11026
Study site
Constanța, 900591
Study site
Timișoara, Timiș County, 300011
Bulgaria3 sites
Study site
Plovdiv, 4002
Study site
Sofia, 1756
Study site
Varna, 9010
Argentina2 sites
Study site
Buenos Aires, Ciudad Auton. de Buenos Aires, C1221 ADC
Study site
Rosario, Santa Fe Province, S2000CKF
About this study
Official title: Randomized, Controlled, Parallel, Prospective Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects, as Applicable, Compared to That of Episodic Treatment
To evaluate the effect of secondary prophylaxis as compared to episodic treatment on bleeding frequency (number of bleeds per year) and on joint damage.
- Conditions
- Hemophilia A
- Being tested
- Recombinant Factor VIII (Kogenate FS, BAY14-2222)
- Keywords
- Hemophilia A
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Factor VIII (Kogenate FS, BAY14-2222)Biological
Prophylaxis treatment includes three times per week administration of 25 IU/kg of Kogenate FS. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
Recombinant Factor VIII (Kogenate FS, BAY14-2222)Biological
Treated according to the Kogenate FS package insert indications and study physician recommendations
| Study group | Role | What they receive |
|---|---|---|
| Recombinant Factor VIII prophylaxis treatment | Experimental | Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater. Receives: Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222) |
| Recombinant Factor VIII on-demand treatment | Experimental | Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations. Receives: Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bleeding Frequency (Number of Total Bleeds)
Measured: After the last enrolled patient has been in the study for 1 year. At the cut-off, the median follow-up duration was 616 days (minimum was 111 days and maximum was 1109 days)
Secondary outcomes (2)
Change From Baseline to 3 Years in the MRI (Magnetic Resonance Imaging) Scale.
The Extended MRI Scale total score has a range between 0 (normal unaffected joint) to 45 (maximal joint damage) points. It is composed of 2 domains, the soft tissue domain with a maximum of 9 points and the osteochondral domain with a maximum of 36 points. A single score for each subject was to be calculated from the sum of both domains and the average over all joints for the Extended MRI endpoint. Higher MRI score denotes greater joint structure damage thus a positive change from baseline means worsening.
Measured: Baseline and 3 years
Change From Baseline to 3 Years in the Colorado Adult Joint Assessment Scale
The total joint score is derived for each of six joints: left and right sides for knees (score: 0-25), ankles (score: 0-25), and elbows (score: 0-21). Higher CAJAS (Colorado Adult Joint Assessment Scale) score denotes greater joint structure damage thus a positive change from baseline means worsening. CAJAS total score is the sum of all 6 joints, ranging from 0 (best possible outcome) to 142 (worst possible outcome).
Measured: Baseline and 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2008 (estimated)
- Study startMar 2008
- Primary completionSep 2011
- Study completionNov 2013
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 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 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
- NCT00623480
- Sponsor's protocol ID
- 12800
- Other IDs
- 2008-000985-21, 2008
- Acronym
- SPINART
- Status last verified
- Nov 2014
- First submitted
- 4 Feb 2008
- Last updated
- 17 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Manco-Johnson MJ, Kempton CL, Reding MT, Lissitchkov T, Goranov S, Gercheva L, Rusen L, Ghinea M, Uscatescu V, Rescia V, Hong W. Randomized, controlled, parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J Thromb Haemost. 2013 Jun;11(6):1119-27. doi: 10.1111/jth.12202.
PubMed 23528101Manco-Johnson MJ, Lundin B, Funk S, Peterfy C, Raunig D, Werk M, Kempton CL, Reding MT, Goranov S, Gercheva L, Rusen L, Uscatescu V, Pierdominici M, Engelen S, Pocoski J, Walker D, Hong W. Effect of late prophylaxis in hemophilia on joint status: a randomized trial. J Thromb Haemost. 2017 Nov;15(11):2115-2124. doi: 10.1111/jth.13811. Epub 2017 Oct 10.
PubMed 28836341
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Controlled, Parallel, Prospective Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects, as Applicable, Compared to That of Episodic Treatment
- ClinicalTrials.gov ID
- NCT00623480
- Acronym / sponsor ID
- SPINART / 12800
- Conditions
- Hemophilia A
- Keywords
- Hemophilia A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- Mar 2008
- Primary completion
- Sep 2011 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 26 Feb 2008 (estimated)
- Results
- Posted 7 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the effect of secondary prophylaxis as compared to episodic treatment on bleeding frequency (number of bleeds per year) and on joint damage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Recombinant Factor VIII prophylaxis treatment | Experimental | Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater. |
| Recombinant Factor VIII on-demand treatment | Experimental | Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations. |
Who may qualify
- Ages
- 12 to 50 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- Males aged 12 to 50 years (US and Argentina)
- Males aged 18 to 50 years (other countries)
- Subjects with severe hemophilia A (<1% FVIII:C) as confirmed by the central lab from a sample obtained at least 96 hours after FVIII administration wash-out. Allow for the inclusion of a maximum of 10% (n=8) of patients with 1-2% FVIII:C baseline levels as long as they exhibit clinical severity and comply with all other inclusion criteria.
- Subjects with at least 150 prior exposure days with any FVIII
- Subjects who have been on episodic treatment and no known regular prophylaxis treatment for more than 12 consecutive months in the previous 5 years
Key exclusion criteria (14 listed)
- Subjects with any other bleeding disease besides hemophilia A (i.e. von Willebrand disease)
- Subjects with thrombocytopenia (platelets < 100,000/mm3)
- Subjects with abnormal renal function (Cockcroft-Gault Creatinine Clearance value of 60 mL/min or lower)
- Subjects with active hepatic disease (Aspartate aminotransferase [AST] or Alanine aminotransferase [ALT] > 5xUpper Limit of Normal (ULN))
- Subjects on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study (the following drugs are however allowed: interferon-a treatment for Hepatitis C virus (HCV), Highly active anti-retroviral therapy (HAART) therapy for human immunodeficiency virus (HIV) and/or a total of two courses of pulse treatment with steroids for a maximum of 7 days at 1mg/kg or less)
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 |
|---|---|---|
| Recombinant Factor VIII (Kogenate FS, BAY14-2222)Prophylaxis treatment includes three times per week administration of 25 IU/kg of Kogenate FS. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) exhibiting a bleeding frequency of 12 bleeding episodes per year or greater. | Biological | Recombinant Factor VIII prophylaxis treatment |
| Recombinant Factor VIII (Kogenate FS, BAY14-2222)Treated according to the Kogenate FS package insert indications and study physician recommendations | Biological | Recombinant Factor VIII on-demand treatment |
Primary outcome
Bleeding Frequency (Number of Total Bleeds)
Time frame: After the last enrolled patient has been in the study for 1 year. At the cut-off, the median follow-up duration was 616 days (minimum was 111 days and maximum was 1109 days)
2 secondary outcomes
Change From Baseline to 3 Years in the MRI (Magnetic Resonance Imaging) Scale.
Time frame: Baseline and 3 years
Change From Baseline to 3 Years in the Colorado Adult Joint Assessment Scale
Time frame: Baseline and 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23528101Manco-Johnson MJ, Kempton CL, Reding MT, Lissitchkov T, Goranov S, Gercheva L, Rusen L, Ghinea M, Uscatescu V, Rescia V, Hong W. Randomized, controlled, parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J Thromb Haemost. 2013 Jun;11(6):1119-27. doi: 10.1111/jth.12202.
- Derived from this study: PubMed 28836341Manco-Johnson MJ, Lundin B, Funk S, Peterfy C, Raunig D, Werk M, Kempton CL, Reding MT, Goranov S, Gercheva L, Rusen L, Uscatescu V, Pierdominici M, Engelen S, Pocoski J, Walker D, Hong W. Effect of late prophylaxis in hemophilia on joint status: a randomized trial. J Thromb Haemost. 2017 Nov;15(11):2115-2124. doi: 10.1111/jth.13811. Epub 2017 Oct 10.
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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
38 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Recombinant Factor VIII (Kogenate FS, BAY14-2222) in people with Hemophilia A, run by Bayer at 38 sites in 4 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 11 inclusion and 14 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 17 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Romania, Bulgaria, Argentina. 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 7 Aug 2013). 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?
Bleeding Frequency (Number of Total Bleeds) (time frame: After the last enrolled patient has been in the study for 1 year. At the cut-off, the median follow-up duration was 616 days (minimum was 111 days and maximum was 1109 days)). 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 NCT00623480, 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 17 Nov 2014.