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Hemophilia APhase 2/3PROTECT-VIIINCT01580293

A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A

A Phase 2/3 study testing BAY94-9027 in people with Hemophilia A, run by Bayer at 59 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Haemophilia A is an inherited disorder in which one of the proteins, Factor VIII, needed to form blood clots is missing or not present in sufficient levels. In a person with haemophilia A, the clotting process is slowed and the person experiences bleeds that can result in serious problems and potential disability. 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?
BAY94-9027
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
59 sitesin 20 countries
Study dates
23 Apr 2012to 21 Nov 2019
Phase
Phase 2/3
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; 12-65 years of age
  • Subjects with severe hemophilia A
  • Previously treated with factor VIII for a minimum of 150 exposure days

Who cannot join

  • Inhibitors to FVIII (current evidence or history)
  • Any other inherited or acquired bleeding disorder in addition to Hemophilia A
  • Platelet count < 100,000/mm3
  • Creatinine > 2x upper limit of normal or AST/ALT (aspartate aminotransferase/alanine aminotransferase) > 5x upper limit of normal

Trial locations and contacts

59 sites in 20 countries.

59 sites in 20 countries

United States14 sites
  • Study site

    Chicago, Illinois, 60612

  • Study site

    Cincinnati, Ohio, 45229-3039

  • Study site

    Cleveland, Ohio, 44106-6007

  • Study site

    Columbus, Ohio, 43205

  • Study site

    Detroit, Michigan, 48202

  • Study site

    Hershey, Pennsylvania, 17033

  • Study site

    Jacksonville, Florida, 32207

  • Study site

    Miami, Florida, 33136

  • Study site

    Minneapolis, Minnesota, 55455

  • Study site

    Richmond, Virginia, 23298-0155

  • Study site

    Sacramento, California, 95817

  • Study site

    San Diego, California, 92103-8651

  • Study site

    Syracuse, New York, 13210

  • Study site

    Tucson, Arizona, 85724-5024

Other trials in United States

Japan6 sites
  • Study site

    Hiroshima, 734-8551

  • Study site

    Kashihara, Nara, 634-8522

  • Study site

    Nagoya, Aichi-ken, 466-8560

  • Study site

    Nishinomiya, Hyōgo, 663-8501

  • Study site

    Shinjuku-ku, Tokyo, 160-0023

  • Study site

    Suginami, Tokyo, 167-0035

Other trials in Japan

France4 sites
  • Study site

    Bron, 69677

  • Study site

    Marseille, 13005

  • Study site

    Reims, 51092

  • Study site

    Rennes, 35033

Other trials in France

Italy4 sites
  • Study site

    Milan, Lombardy, 20122

  • Study site

    Naples, Campania, 80131

  • Study site

    Rome, Lazio, 00161

  • Study site

    Turin, Piedmont, 10126

Other trials in Italy

Netherlands4 sites
  • Study site

    Amsterdam, 1105 AZ

  • Study site

    Groningen, 9713 GZ

  • Study site

    Maastricht, 6229 HX

  • Study site

    The Hague, 2545 CH

Other trials in Netherlands

South Korea4 sites
  • Study site

    Busan, Busan Gwang''yeogsi, 49241

  • Study site

    Daejeon, 35233

  • Study site

    Seoul, 03722

  • Study site

    Seoul, 05278

Other trials in South Korea

Singapore3 sites
  • Study site

    Singapore, 119228

  • Study site

    Singapore, 169608

  • Study site

    Singapore, 229 899

Other trials in Singapore

Taiwan3 sites
  • Study site

    Changhua, 50006

  • Study site

    Taipei, 100

  • Study site

    Taipei, 11217

Other trials in Taiwan

United Kingdom3 sites
  • Study site

    London, SE1 7EH

  • Study site

    Newcastle upon Tyne, Vale of Glamorgan, the, NE1 4LP

  • Study site

    Sheffield, S10 2JF

Other trials in United Kingdom

Colombia2 sites
  • Study site

    Baranquilla, Atlántico, 080020

  • Study site

    Medellín, Antioquia, 050030

Other trials in Colombia

Germany2 sites
  • Study site

    Bonn, North Rhine-Westphalia, 53127

  • Study site

    Heidelberg, Baden-Wurttemberg, 69004

Other trials in Germany

Turkey (Türkiye)2 sites
  • Study site

    Ankara, 06100

  • Study site

    Izmir, 35100

Other trials in Turkey (Türkiye)

Austria1 site
  • Study site

    Vienna, 1090

Other trials in Austria

Belgium1 site
  • Study site

    Bruges, 8000

Other trials in Belgium

Canada1 site
  • Study site

    London, Ontario, N6A 5W9

Other trials in Canada

Denmark1 site
  • Study site

    Aarhus N, 8200

Other trials in Denmark

Israel1 site
  • Study site

    Ramat Gan, 5262000

Other trials in Israel

Norway1 site
  • Study site

    Oslo, 0372

Other trials in Norway

Poland1 site
  • Study site

    Wroclaw, 50-367

Other trials in Poland

Romania1 site
  • Study site

    Timișoara, 300011

Other trials in Romania

About this study

Official title: A Phase II/III, Multicenter, Partially Randomized, Open Label Trial Investigating Safety and Efficacy of On-demand and Prophylactic Treatment With BAY94-9027 in Severe Hemophilia A

Haemophilia A is an inherited disorder in which one of the proteins, Factor VIII, needed to form blood clots is missing or not present in sufficient levels. In a person with haemophilia A, the clotting process is slowed and the person experiences bleeds that can result in serious problems and potential disability.

The current standard treatment for severe haemophilia A is regularly scheduled infusion of FVIII to keep levels high enough to prevent bleeding. Due to the short half-life of FVIII, prophylaxis may require treatment as often as every other day.

Read more

In this trial safety and efficacy of a long-acting recombinant factor VIII molecule is evaluated in subjects with severe Hemophilia A.

120-140 patients will receive open label treatment with long-acting rFVIII either on-demand to treat bleeds or prophylactically for 36 weeks in the main trial plus an optional extension to continue treatment for at least 100 total exposure days (ED). Patients on prophylactic treatment will receive study drug at dosing intervals between once and twice a week depending on their observed bleeding. Patients will attend the treatment centre for routine blood samples and be required to keep an electronic diary.

Male patients aged 12-65, with severe hemophilia A, previously treated with FVIII for at least 50 exposure days may be eligible for this study.

Read the detailed description

Subjects in prophylactic treatment arms will undergo clinical evaluation at 10 weeks. Those with adequate control of bleeding will undergo randomization to every 5 or 7 day infusion. Those with continued bleeding will remain in treatment arm and have an increase in dose.

Part B-major surgery - optional sub study included to collect information on efficacy of BAY94-9027 in major surgical setting. Due to rarity of surgery in this population, enrollment to this sub-study may be independent of participation in main study.

Conditions
Hemophilia A
Being tested
BAY94-9027
Keywords
Hemophilia A, factor VIII, prophylaxis
Medical subject headings
Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BAY94-9027Biological

    Intravenous infusion of BAY94-9027

Study groups in NCT01580293
Study groupRoleWhat they receive
Arm 1ExperimentalOn-demand treatment of BAY94-9027 at individual dose and number of infusions based upon location and severity of bleeds
Receives: Biological: BAY94-9027
Arm 2ExperimentalProphylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by 2 infusions per week over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED
Receives: Biological: BAY94-9027
Arm 3ExperimentalProphylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by infusion every 5 days over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED
Receives: Biological: BAY94-9027
Arm 4ExperimentalProphylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by infusion every 7 days over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED
Receives: Biological: BAY94-9027

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Annualized Number of Total Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A, Main Trial

    Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds. A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the annualized bleeding rate (ABR).

    Measured: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Secondary outcomes (18)
  1. Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A

    A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the ABR.

    Measured: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

  2. Annualized Number of Total Bleeds in On-demand Treatment Arm and in Each Prophylaxis Arm, Part A, Extension

    Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds.

    Measured: at least 100 total exposure days acquired, median time 3.9 years up to 7 years maximum

  3. Number of Participants Developed Human Coagulation Factor VIII (FVIII) Inhibitor - Part A

    FVIII inhibitor testing was done according to the Nijmegen modified Bethesda assay. A positive inhibitor test was defined with a threshold of ≥0.6 Bethesda unit (BU) at the central laboratory.

    Measured: Weeks 0 to 36 during Part A

  4. Number of Bleeds Requiring 1, 2 or >= 3 Infusions to Control the Bleed - Part A

    Number of bleeds requiring 1, 2 or >= 3 infusions to control the bleeding

    Measured: Weeks 0 to 36

  5. Number of Bleeds According to Locations - Part A

    Bleed locations were categorised as joint, muscle, skin/mucosa, internal, others and missing.

    Measured: Weeks 0 -36

  6. Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A

    Measured: Weeks 0 to 36

  7. Number of Bleeds According to Participant's Assessment of Response to Treatment - Part A

    Response to treatment was assessed by participant as excellent, good, moderate, poor or missing during Part A of the study.

    Measured: Weeks 0 to 36 during Part A

  8. Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose Per Kilogram Per Year - Part A

    For prophylaxis patients, the dose is related to all infusions.

    Measured: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

  9. Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram Per Infusion - Part A

    For prophylaxis patients, the dose per infusion related to prophylaxis infusion.

    Measured: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

  10. Number of Participants Requiring an Increase in Dose Frequency, or Dose Increase, During Weeks 10 to 36 - Part A

    Measured: Weeks 10 to 36 during Part A

  11. Number of Surgeries According to Physician's Assessment of Adequacy of Hemostasis in Major Surgery - Part B

    Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill. Adequacy of hemostasis was assessed as excellent, good, moderate or poor, by the surgeon or interventionalist during Part B of the study.

    Measured: Day of surgery

  12. Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram Per Infusion for Major Surgery - Part B

    Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill. Total dose per kilogram per Infusion was expressed in international units per kilogram per infusion (IU/kg/infusion).

    Measured: Up to 3 weeks post-surgery during Part B

  13. Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery - Part B

    Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.rFVIII usage expressed as number of infusions and IU/kg per year, as well as IU/kg per event (surgery) was assessed by investigator.

    Measured: Up to 3 weeks post-surgery during Part B

  14. Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay - Part A

    Cmax: Maximum observed drug concentration following an infusion of 60 IU/kg

    Measured: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

  15. Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay - Part A

    AUC: The total area under the plasma concentration versus time curve following an infusion of 60 IU/kg .

    Measured: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

  16. Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay - Part A

    t1/2: Terminal half-life is the time the plasma concentration during terminal phase is halved following an infusion of 60 IU/kg .

    Measured: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

  17. Overall Human Coagulation Factor VIII (FVIII) Recovery Value by Chromogenic Assay - Part A

    Recovery was calculated by the following formula: Recovery = (post-infusion FVIII activity - pre-infusion FVIII activity ) * weight / dose (in IU). Recovery is the increase of FVIII activity after the injection normalized by dose: IU/dl per IU/kg = kg/dL

    Measured: Weeks 0 to 36 during Part A

  18. Change From Baseline in Quality of Life by Hemophilia Specific Quality of Life Instrument or Questionnaire for Adults (Haemo-QoL-A) Overall Score at Week 36 - Part A

    Quality of life (QoL) was measured by the Haemo-QoL-A overall score, which ranged from 0 (the worst condition) to 100 (the best condition).

    Measured: Week 0 (baseline) and Week 36 during Part A

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2012 (estimated)
  2. Study start23 Apr 2012
  3. Primary completion13 Jun 2014
  4. Study completion21 Nov 2019

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01580293
Sponsor's protocol ID
13024
Other IDs
2011-005210-11
Acronym
PROTECT-VIII
Status last verified
Nov 2023
First submitted
28 Mar 2012
Last updated
7 Nov 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Baumann A, Piel I, Hucke F, Sandmann S, Hetzel T, Schwarz T. Pharmacokinetics, excretion, distribution, and metabolism of 60-kDa polyethylene glycol used in BAY 94-9027 in rats and its value for human prediction. Eur J Pharm Sci. 2019 Mar 15;130:11-20. doi: 10.1016/j.ejps.2019.01.015. Epub 2019 Jan 14.

    PubMed 30654111
  • Lalezari S, Reding MT, Pabinger I, Holme PA, Negrier C, Chalasani P, Shin HJ, Wang M, Tseneklidou-Stoeter D, Maas Enriquez M. BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results. Haemophilia. 2019 Nov;25(6):1011-1019. doi: 10.1111/hae.13853. Epub 2019 Oct 17.

    PubMed 31621991
  • Reding MT, Ng HJ, Poulsen LH, Eyster ME, Pabinger I, Shin HJ, Walsch R, Lederman M, Wang M, Hardtke M, Michaels LA. Safety and efficacy of BAY 94-9027, a prolonged-half-life factor VIII. J Thromb Haemost. 2017 Mar;15(3):411-419. doi: 10.1111/jth.13597. Epub 2017 Feb 22.

    PubMed 27992112
  • Reding MT, Pabinger I, Holme PA, Maas Enriquez M, Mancuso ME, Lalezari S, Miesbach W, Di Minno G, Klamroth R, Hermans C. Efficacy and safety of damoctocog alfa pegol prophylaxis in patients ⩾40 years with severe haemophilia A and comorbidities: post hoc analysis from the PROTECT VIII study. Ther Adv Hematol. 2023 Apr 22;14:20406207231166779. doi: 10.1177/20406207231166779. eCollection 2023.

    PubMed 37113811

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing BAY94-9027 in people with Hemophilia A, run by Bayer at 59 sites in 20 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 3 inclusion and 4 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 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in United States, Japan, France, Italy, Netherlands and 15 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 6 Dec 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 Total Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A, Main Trial (time frame: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A). 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 NCT01580293, which also lists 4 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 7 Nov 2023.

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