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BAX 802 in CHA With Inhibitors (CHAWI)

Primary Purpose

Hemophilia A

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Antihemophilic Factor (Recombinant), Porcine Sequence (BAX 802)

About this trial

This is an interventional treatment trial for Hemophilia A

Eligibility Criteria

12 Years - 75 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria

Participant requires a major or minor elective surgical, dental or other invasive procedure
Participant is male and ≥ 12 to ≤ 75 years old at the time of screening
Participant has provided signed informed consent (and assent for adolescent participants, as applicable) in accordance with local regulatory requirements
Participant has severe (factor VIII (FVIII) level < 1%) or moderately severe (FVIII level ≤ 2%) congenital hemophilia A (CHA) with inhibitors to human factor VIII (hFVIII) of ≥ 0.6 Bethesda units (BU), as tested at screening at the central laboratory
Participant is not currently receiving or has recently received (< 30 days) immune tolerance induction (ITI) therapy
Participant has a Karnofsky performance score of ≥ 60 at screening
Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3 at screening
Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing; or HCV+ with chronic stable hepatitis disease. Positive serologies will be confirmed by PCR testing.
Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria

The participant requires emergency surgery
Severe chronic liver dysfunction or disease (e.g., ≥ 5 × upper limit of normal [ULN] alanine aminotransferase [ALT], as confirmed by central laboratory at screening or a documented prothrombin time/international normalized ratio [PT/INR] > 1.5)
Clinically symptomatic renal disease (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening
Anti-porcine factor VIII (pFVIII) inhibitor > 10 BU prior to surgery
Platelet count < 100,000/μL at screening
Participant has another active coagulation disorder, other than hemophilia A, as per the medical history
Planned use of α-interferon with or without ribavirin for HCV infected patients or planned use of a protease inhibitor for HIV infected patients. Patients currently taking any of these medications for ≥ 30 days are eligible
Known hypersensitivity to recombinant porcine factor VIII (rpFVIII), or hamster or murine proteins
Participant has an ongoing or recent (within 3 months of screening) thrombo-embolic disease, fibrinolysis or disseminated intravascular coagulation (DIC)
Participant has been exposed to an IP within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study
Participant is unable to tolerate quantity of blood to be drawn for protocol procedures
Participant is a family member or employee of the Investigator.

Sites / Locations

Bleeding and Clotting Disorders Institute
Wake Forest University Baptist Medical Center
Case Western Reserve University
UMHAT 'Tsaritsa Yoanna - ISUL', EAD
UMHATEM 'N.I. Pirogov', EAD
Hopital Maisonneuve-Rosemont d/b/a CIUSSS de l'Est-de-l'Île-de-Montréal
Universitaetsklinikum Bonn AoeR
Zentrum für Hämostaseologie, Universitätsklinikum Leipzig AöR
Presidio Ospedaliero di Castelfranco Veneto
Azienda Ospedaliera Universitaria Careggi
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Azienda Ospedaliera di Padova
UMC Utrecht
Oslo Universitetssykehus - Rikshospitalet
Instytut Hematologii i Transfuzjologii-1-1Y7-1347
FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA.
Bleeding Disorders Unit and Clinical Haematology Service at Charlotte Maxeke JHB Academic Hospital
Hospital Universitari i Politecnic La Fe
Complejo Hospitalario Universitario A Coruña
Hospital Universitario La Paz
Ankara University Medical Faculty
Ege University Medical Faculty
Ege University Medical Faculty
Kocaeli University Medical Faculty

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BAX 802 in Surgery

Arm Description

Participants who are undergoing major or minor elective surgical, dental, or other invasive procedures.

Outcomes

Primary Outcome Measures

Percentage of Surgeries With a "Good" or "Excellent" Response as Measured by the Global Hemostatic Efficacy Assessment (GHEA) Score

GHEA score consisted of 3 individual rating scales: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, and (3) Overall Peri-operative Efficacy Assessment Scale. Scales 1 and 2 was performed by the operating surgeon on Day 1, and Scale 3 was performed by the investigator on Day 14. Each rating scale was based on 4 points scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). Total score ranged from 0 to 9, where scores evaluated as: excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2). The scores of 3 individual ratings scales were added together to form a GHEA score. For a GHEA score of 7 to be rated "excellent" with no individual assessment scores less than (<) 2 and at least 1 assessment score equal to (=) 3; otherwise a score of 7 was rated "good". Percentage of Surgeries With a "Good" or "Excellent" response as measured by the GHEA score were reported.

Secondary Outcome Measures

Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period

Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (in milliliter [mL]) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Actual blood loss, estimated volume of expected average blood loss and expected maximum blood loss during each operative period was reported.

Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period

Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Ratio of actual blood loss and estimated volume of expected average blood loss during each operative period was reported.

Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period

Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Ratio of actual blood loss and expected maximum blood loss during each operative period was reported.

Percentage of Major Surgeries With Good or Excellent Hemostatic Score

Percentage of major surgeries with good or excellent hemostatic score was analyzed by GHEA score. It consisted of 3 individual ratings: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, (3) Postoperative Efficacy Assessment Scale. Ratings 1 and 2 was performed by the operating surgeon on Day 1, and Rating 3 was performed by the investigator on Day 14. Each rating scale was based on 4 point scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). The scores of each of the 3 individual ratings scales, was added together to form a GHEA score. Total score ranged from 0 to 9 where scores evaluated as excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2). Hemostatic efficacy success was defined as "excellent" or "good "outcome for >=70% of hemostatic efficacy assessments. Percentage of major surgeries with good or excellent hemostatic score were reported.

Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period

Body-weight adjusted dose equals to amount infused/body-weight (kilogram [kg]), where amount infused as amount of drug infused (International Units [IU]) and body-weight as the last available body-weight (kg) prior to the infusion. Pre-operative defined as period prior to surgery. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Average daily weight-adjusted dose of BAX 802 per participant during each operative period was reported.

Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period

Body-weight adjusted dose equals to amount infused/body-weight (kg), where amount infused as amount of drug infused (IU) and body-weight as the last available body-weight (kg) prior to the infusion. Pre-operative defined as period prior to surgery. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Total weight-adjusted dose of BAX 802 per participant during each operative period was reported.

Volume of Blood Products Transfused

The volume (in mL) of blood products transfused from initiation of the intervention to discharge or Day 14 (whichever came earlier) was reported.

Number of Participants With De Novo Inhibitors

De novo inhibitor was defined as a post-baseline inhibitor titer to FVIII (hFVIII or porcine factor VIII [pFVIII])of >=0.6 Bethesda units per milliliter (BU/mL) given a baseline of <0.6 BU/mL. Number of participants with de novo inhibitors were reported.

Number of Participants With Anamnestic Reactions

An anamnestic reaction was defined as an increase from a measurable baseline (>0.6 BU/mL) in the inhibitor titer to FVIII (human or porcine) of >=10 BU/mL. Number of participants with anamnestic reactions were reported.

Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to pFVIII

The assessment of inhibitory antibodies (immunoglobulin G [IgG] and immunoglobulin M [IgM]) to pFVIII was determined using Bethesda assay, and assessment of binding antibodies (IgG and IgM) to pFVIII was determined using validated enzyme-linked immunosorbent assays (ELISAs). Mean change from baseline in inhibitory and binding antibodies to pFVIII was reported.

Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to hFVIII

The assessment of inhibitory antibodies (IgG and IgM) to hFVIII was determined using Bethesda assay, and assessment of binding antibodies (IgG and IgM) to hFVIII was determined using ELISA. Mean change from baseline in inhibitory and binding antibodies to hFVIII was reported.

Number of Participants With Clinically Significant Change From Baseline in Binding Antibodies to Baby Hamster Kidney (BHK) Proteins

The assessment of binding antibodies to BHK proteins was determined using ELISA. Clinical significance was judged by the investigator. Number of participants with clinically significant change from baseline in binding antibodies to BHK proteins were reported.

Number of Participants With Thromboembolic Events

Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream to plug another vessel. Number of participants with thromboembolic events was reported.

Number of Participants With Severe Allergic Reactions

Number of participants with severe allergic reaction (example: anaphylaxis) after administration of study drug were reported.

Number of Participants With Investigational Product (IP) Related Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Serious AE was any untoward medical occurrence (whether considered to be related to study assigned treatment or not) that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital abnormality/birth defect, or was an important medical event. TEAEs was defined as any adverse events (classified by preferred term) that had a start date on or after the first dose of study treatment or that had a start date before the date of first dose of study treatment, but increased in severity after the first dose of study treatment. TEAEs included both serious and non-serious TEAEs.

Number of Participants With Clinically Significant Change From Baseline in Vital Sign

Vital sign parameters included: temperature, pulse rate, respiration rate, systolic and diastolic blood pressure. Any changes in vital signs which were deemed clinically significant was judged by the investigator. Number of participants with clinically significant change from baseline in vital signs were reported.

Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values

Clinical laboratory assessment included hematology and clinical chemistry. Any changes in clinical laboratory results which were deemed clinically significant was judged by the investigator. Number of participants with clinical significant change from baseline in clinical laboratory values were reported.

Full Information

NCT ID

NCT02895945

First Posted

August 15, 2016

Last Updated

October 5, 2021

Sponsor

Baxalta now part of Shire

Collaborators

Baxalta Innovations GmbH, now part of Shire

1. Study Identification

Unique Protocol Identification Number

NCT02895945

Brief Title

BAX 802 in CHA With Inhibitors

Acronym

CHAWI

Official Title

A Phase 3, Multicenter, Open-label Study of the Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in Subjects With Congenital Hemophilia A With Factor VIII Inhibitors Undergoing Surgical or Other Invasive Procedures

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Terminated

Why Stopped

Takeda has determined that the benefit/risk profile does not support continuation of the surgery Study for this specific Congenital Hemophilia A with Inhibitors patient population.

Study Start Date

December 22, 2016 (Actual)

Primary Completion Date

January 22, 2021 (Actual)

Study Completion Date

January 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Baxalta now part of Shire

Collaborators

Baxalta Innovations GmbH, now part of Shire

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of BAX 802 in males with congenital hemophilia A (CHA) with inhibitors who are undergoing major or minor elective surgical, dental, or other invasive procedures.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hemophilia A

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BAX 802 in Surgery

Arm Type

Experimental

Arm Description

Participants who are undergoing major or minor elective surgical, dental, or other invasive procedures.

Intervention Type

Biological

Intervention Name(s)

Antihemophilic Factor (Recombinant), Porcine Sequence (BAX 802)

Other Intervention Name(s)

BAX 802, recombinant porcine factor VIII, Obizur, rpFVIII

Intervention Description

In case of major surgery, FVIII target level is ≥80% for major surgeries/ procedures and ≥50% for minor surgeries/ procedures.

Primary Outcome Measure Information:

Title

Percentage of Surgeries With a "Good" or "Excellent" Response as Measured by the Global Hemostatic Efficacy Assessment (GHEA) Score

Description

Time Frame

Day 1 up to discharge or Day 14 (whichever was earlier)

Secondary Outcome Measure Information:

Title

Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period

Description

Time Frame

Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)

Title

Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period

Description

Time Frame

Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)

Title

Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period

Description

Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Ratio of actual blood loss and expected maximum blood loss during each operative period was reported.

Time Frame

Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)

Title

Percentage of Major Surgeries With Good or Excellent Hemostatic Score

Description

Time Frame

Day 1 up to discharge or Day 14 (whichever was earlier)

Title

Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period

Description

Time Frame

Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier)

Title

Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period

Description

Time Frame

Title

Volume of Blood Products Transfused

Description

The volume (in mL) of blood products transfused from initiation of the intervention to discharge or Day 14 (whichever came earlier) was reported.

Time Frame

From initiation of the surgery up to discharge or Day 14 (whichever came earlier)

Title

Number of Participants With De Novo Inhibitors

Description

Time Frame

Baseline up end of study (EOS) (up to 44 months)

Title

Number of Participants With Anamnestic Reactions

Description

Time Frame