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Hemophilia APhase 3NCT00157157

Efficacy and Safety Study of a Recombinant Protein-Free Manufactured Factor VIII (rAHF-PFM) in Previously Untreated Hemophilia A Patients

A Phase 3 study testing Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM) in people with Hemophilia A, run by Baxalta now part of Shire at 35 sites in 10 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

The purpose of this study is to evaluate whether Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) is effective and safe in the treatment of hemophilia A patients who have not been treated with factor VIII (FVIII) before. Read more about this study

Who is it for?
Ages Up to 6 years
Conditions the study is for
Hemophilia A
What is being tested?
Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
35 sitesin 10 countries
Study dates
1 Apr 2004to 11 Sep 2009
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 Up to 6 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level <= 2% of normal, as documented at screening
  • The subject is < 6 years of age
  • The subject's legally authorized representative has provided written informed consent

Who cannot join

  • The subject has a history of exposure to factor VIII other than rAHF PFM or more than 3 infusions of commercially available rAHF PFM (i.e., ADVATE) within 28 days prior to screening, as determined by the subject's medical history. Any infusion of factor VIII replacement products prior to the 28-day period excludes the subject from participation
  • The subject has received more than 3 infusions of rAHF PFM (commercially available and/or study product) between screening and prior to the initial recovery infusion
  • The subject has a detectable inhibitor to factor VIII, as measured in the screening sample by the Nijmegen assay in the central laboratory
  • The subject has a history of inhibitor to factor VIII at any time prior to screening
  • The subject has a known hypersensitivity to rAHF PFM
  • The subject has any 1 of the following laboratory abnormalities at the time of screening:
Show all 16Show fewer
  • Platelet count < 100,000/mm^3
  • Hemoglobin concentration < 10 g/dL (100 g/L)
  • Serum creatinine > 1.5 times the upper limit of normal (ULN) for age
  • Total bilirubin > 2 times the ULN for age
  • The subject has an inherited or acquired hemostatic defect other than hemophilia A (e.g., qualitative platelet defect or von Willebrand's disease)
  • The subject is known to be seropositive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV), as determined by the subject's medical history
  • At the time of enrollment, the subject has a clinically significant chronic disease other than hemophilia A
  • The subject is currently participating in another investigational drug study, or has participated in any clinical study involving an investigational drug within 120 days of the screening visit
  • The subject (or the subject's legally authorized representative) is identified by the investigator as being unable or unwilling to cooperate with study procedures
  • The subject has received any blood product, including packed red blood cells (RBC), platelets, plasma, or cryoprecipitate

Trial locations and contacts

35 sites in 10 countries.

35 sites in 10 countries

United States17 sites

  • Study site

    Ann Arbor, Michigan

  • Study site

    Atlanta, Georgia

  • Study site

    Chicago, Illinois

  • Study site

    Detroit, Michigan

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Iowa City, Iowa

  • Study site

    Little Rock, Arkansas

  • Study site

    Los Angeles, California

  • Study site

    Minneapolis, Minnesota

  • Study site

    New Hyde Park, New York

  • Study site

    New Orleans, Louisiana

  • Study site

    New York, New York

  • Study site

    Peoria, Illinois

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Phoenix, Arizona

  • Study site

    Washington D.C., District of Columbia

Other trials in United States

France6 sites

  • Study site

    Caen

  • Study site

    Le Kremlin-Bicêtre

  • Study site

    Lyon

  • Study site

    Marseille

  • Study site

    Nantes

  • Study site

    Paris

Other trials in France

Germany4 sites

  • Study site

    Bremen

  • Study site

    Frankfurt

  • Study site

    Hanover

  • Study site

    Münster

Other trials in Germany

United Kingdom2 sites

  • Study site

    Cardiff, Wales

  • Study site

    London

Other trials in United Kingdom

Austria1 site

  • Study site

    Vienna

Other trials in Austria

Canada1 site

  • Study site

    Toronto, Ontario

Other trials in Canada

Italy1 site

  • Study site

    Milan

Other trials in Italy

Puerto Rico1 site

  • Study site

    San Juan

Other trials in Puerto Rico

Spain1 site

  • Study site

    Barcelona

Other trials in Spain

Sweden1 site

  • Study site

    Stockholm

Other trials in Sweden

About this study

Official title: Recombinant Antihemophilic Factor Manufactured and Formulated Without Added Human or Animal Proteins (rAHF-PFM): Evaluation of Immunogenicity, Efficacy, and Safety in Previously Untreated Patients With Hemophilia A

The purpose of this study is to evaluate whether Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) is effective and safe in the treatment of hemophilia A patients who have not been treated with factor VIII (FVIII) before.

Conditions
Hemophilia A
Being tested
Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM)
Keywords
Factor VIII Deficiency
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 Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM)Biological

    Treatment regimens were determined by the investigator, and may have been any combination of standard prophylaxis (25 to 50 IU/kg body weight, 3 to 4 times per week), investigator-determined prophylaxis, and/or on-demand treatment (dose selected by investigator).

    The treatment of bleeding episodes and perioperative management was at the discretion of the investigator and consistent with the institution's standard of care.

    For incremental recovery assessments, a single infusion at 50 +/- 5 IU/kg was to be given.

    Immune tolerance induction (ITI) therapy for subjects who developed factor VIII inhibitors was at the discretion of the investigator, based on the institution's guidelines or described in peer-reviewed literature, and was to be approved by the sponsor's medical director.

    rAHF-PFM was to be administered intravenously via bolus infusion, except for perioperative management when it may have been given either by continuous or bolus infusion.

Study groups in NCT00157157
Study groupRoleWhat they receive
Single Arm - All ParticipantsExperimentalAll subjects enrolled in the study who meet the eligibility criteria.
Receives: Biological: Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM)

What is being measured

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

  1. Factor VIII Inhibitor Development

    Percentage of treated participants who developed factor VIII inhibitors

    Measured: Assessed during study period which was to be at least 75 exposure days or 3 years (whichever came first)

Secondary outcomes (10)

  1. Bleeding Episodes Treated With 1 to ≥4 Infusions

    The number of bleeding episodes treated with 1, 2, 3, or ≥4 infusions of rAHF-PFM to achieve adequate hemostasis

    Measured: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)

  2. Assessment of Hemostasis for Treatment of Bleeding Episodes

    Number of rAHF-PFM-treated bleeding episodes with treater assessment of hemostasis (4-point ordinal scale): Excellent: Full pain relief \& bleeding cessation within ~8 hrs of 1 infusion. Additional infusions may have been given to maintain hemostasis; Good: Definite pain relief and/or improvement in bleeding within ~8 hrs after infusion. Possibly requires >1 infusion for complete resolution; Fair: Probable or slight relief of pain \& slight improvement in bleeding within ~8 hrs after infusion. Requires >1 infusion for complete resolution; or None: No improvement or condition worsens.

    Measured: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)

  3. Annualized Rate of Bleeding Episodes

    Number of bleeding episodes per subject annualized over 1 year for all etiologies

    Measured: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)

  4. Weekly rAHF-PFM Utilization

    Weight-Adjusted Weekly Dose for Prophylaxis, On-Demand Treatment, and Perioperative Management. rAHF-PFM dose determined by the investigator (ie: standard regimen [25-50 IU/kg body weight, 3-4 times per week]; modified prophylactic regimen [dose and frequency selected by investigator] or on-demand treatment [dose selected by investigator]). Dosing to treat BEs was at investigator's discretion and in accordance with institution's standard of care. rAHF-PFM was administered I.V. via bolus infusion, except for perioperative management when it was given either by continuous or bolus infusion.

    Measured: Reported during study period which was to be at least 75 exposure days or 3 years (whichever came first)

  5. In Vivo Incremental Recovery

    Change in factor VIII concentration from pre- to post-infusion at initial and termination study visits.

    Measured: 30 minutes pre-infusion to 30 minutes post-infusion

  6. Assessment of Intra-operative Hemostasis

    Number of surgical procedures managed with rAHF-PFM and with surgeon's assessment of hemostasis based on a 4-point ordinal scale: Excellent: ≤ average predicted blood loss for matched procedures in healthy individuals Good: > average predicted blood loss, but ≤ maximal predicted blood loss for matched procedures in healthy individuals Fair: > maximal predicted blood loss for matched procedures in healthy individuals, and hemostasis was achieved None: uncontrolled hemostasis with proper dosing, necessitating a change in treatment regimen

    Measured: Assessed at the time of discharge from recovery room

  7. Assessment of Postoperative Hemostasis

    Number of surgical procedures managed with rAHF-PFM and with investigator's assessment of hemostasis based on a 4-point ordinal scale: Excellent: hemostasis was as good as or better than other licensed factor VIII products for matched procedure Good: hemostasis was probably as good as other licensed factor VIII products for matched procedure Fair: hemostasis was clearly < optimal for matched procedure, without need to change regimen None: bleeding from inadequate response with proper dosing, necessitating a change in regimen

    Measured: Assessed at the time of discharge from hospital or clinic

  8. Assessment of Blood Loss During Surgical Procedures

    Percentage of actual intraoperative blood loss compared to preoperatively predicted average and maximal blood loss in hemostatically normal matched individuals (from institutional blood bank records)

    Measured: Predicted volumes preoperatively estimated and actual volumes intraoperatively recorded

  9. Adverse Events Deemed Related to Treatment

    Percentage of participants who reported AEs deemed related to treatment with rAHF-PFM

    Measured: Reported during the study period which was to be at least 75 exposure days or 3 years (whichever came first)

  10. Development of Antibodies to Heterologous Proteins

    Percentage of treated participants who developed antibodies to heterologous proteins (ie, Chinese Hamster Ovary Cell Protein, Murine IgG, or Recombinant Human VWF)

    Measured: Assessed at baseline, throughout the duration of the study, which was to be at least 75 exposure days or 3 years (whichever came first), and at the termination visit.

Timeline

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

  1. First posted12 Sep 2005 (estimated)
  2. Study start1 Apr 2004
  3. Primary completion11 Sep 2009
  4. Study completion11 Sep 2009

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 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00157157
Sponsor's protocol ID
060103
Other IDs
2004-001623-38, 2004
Status last verified
Apr 2021
First submitted
9 Sep 2005
Last updated
24 May 2021
Data monitoring committee
Yes
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Publications

  • Ewenstein B., Patrone L, Schroth P, Spotts G, Fritsch S, Pavlova B, Ehrlich H. Efficacy of antihemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM) in bleed prevention. J Thromb Haemost. 2007; 5(Suppl 2): P-S-179.

  • Ewenstein B., Patrone L, Schroth P, Spotts G, Fritsch S, Pavlova B, Ehrlich H. Efficacy of antihemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM) in bleed treatment. J Thromb Haemost. 2007; 5(Suppl 2)v: P-S-180.

  • Shapiro A, Gruppo R, Pabinger I, Collins PW, Hay CR, Schroth P, Casey K, Patrone L, Ehrlich H, Ewenstein BM. Integrated analysis of safety and efficacy of a plasma- and albumin-free recombinant factor VIII (rAHF-PFM) from six clinical studies in patients with hemophilia A. Expert Opin Biol Ther. 2009 Mar;9(3):273-83. doi: 10.1517/14712590902729392.

    PubMed 19216617

  • Auerswald G, Thompson AA, Recht M, Brown D, Liesner R, Guzman-Becerra N, Dyck-Jones J, Ewenstein B, Abbuehl B. Experience of Advate rAHF-PFM in previously untreated patients and minimally treated patients with haemophilia A. Thromb Haemost. 2012 Jun;107(6):1072-82. doi: 10.1160/TH11-09-0642. Epub 2012 Apr 4.

    PubMed 22476554

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Recombinant Antihemophilic Factor Manufactured and Formulated without Added Human or Animal Proteins (rAHF-PFM) in people with Hemophilia A, run by Baxalta now part of Shire at 35 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 3 inclusion and 16 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 24 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, France, Germany, United Kingdom, Austria 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 15 Jul 2011). 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?

Factor VIII Inhibitor Development (time frame: Assessed during study period which was to be at least 75 exposure days or 3 years (whichever came first)). 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 NCT00157157, 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 24 May 2021.

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