Back to resultsRIXUBIS PMS India (RIXUBIS PMS)
Primary Purpose
Hemophilia B
Status
Completed
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
RIXUBIS: On-Demand
RIXUBIS: Prophylaxis
Sponsored by
About this trial
This is an interventional prevention trial for Hemophilia B
Eligibility Criteria
Inclusion Criteria
- The participant or legally authorized representative (in case of study participants <18 years of age) gave written informed consent to participate in the study.
- Participant has hemophilia B.
Participant is defined as previously-treated patient (PTP):
- Participant aged ≥ 6 years that has been previously treated with plasma-derived and/or recombinant factor IX (FIX) concentrate(s) for a minimum of 150 exposure days (EDs).
- Participant aged < 6 years that has been previously treated with plasma-derived and/or recombinant FIX concentrate(s) for a minimum of 50 EDs.
- Participant has no evidence of a history of FIX inhibitors.
- Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
- Participant is hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer will be confirmed by polymerase chain reaction (PCR)), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
- The participant is willing and able to comply with the requirements of the protocol.
Exclusion Criteria
- Participant has known hypersensitivity or presence of any contraindication to RIXUBIS or its excipients including hamster protein.
- Participant has evidence of an ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
- Participant has a history of FIX inhibitors with a titer ≥ 0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay, employed in the respective local laboratory) at any time prior to screening.
- Participant has a detectable FIX inhibitor at screening, with a titer ≥ 0.6 BU as determined by the Nijmegen modification of the Bethesda assay in the central laboratory.
- Participant has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4 hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.
- Participant has severe chronic hepatic dysfunction [eg, ≥ 5 times upper limit of normal alanine aminotransferase (ALT), as confirmed by central laboratory at screening, or a documented INR > 1.5].
- Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
- Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia B.
- Participant's platelet count is < 100,000/mL.
- Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant's safety or compliance.
- Participant is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or α-interferon) other than antiretroviral chemotherapy.
- Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
- Participant is a family member or employee of the investigator.
Sites / Locations
- Sahyadri Super Speciality Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All Study Participants
Arm Description
Study participants with Hemophilia B in India receiving Rixubis
Outcomes
Primary Outcome Measures
Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) Related to RIXUBIS
TEAE was defined as any event not presented prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. A SAE was defined as any untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, life-threatening, required in-patient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event that was not immediately life-threatening or resulted in death or required hospitalization but jeopardize the participant or required medical or surgical intervention to prevent any of the above outcomes. Relatedness to study drug was based on physician discretion. Number of participants with serious TEAEs related to RIXUBIS were reported.
Secondary Outcome Measures
Number of Participants With TEAEs Related to RIXUBIS
TEAE was defined as any event not presented prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. Relatedness to study drug was based on physician discretion. Number of participants with TEAEs related to RIXUBIS were reported.
Number of Participants With Clinically Significant Laboratory Abnormalities
Clinical laboratory evaluations included clinical chemistry (biochemistry and endocrinology), hematology and urinalysis. Any change in clinical laboratory abnormalities which were deemed clinically significant by the investigator were recorded as TEAEs (defined as any event not presented prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments).
Number of Participants Who Developed Binding Antibodies (Immunoglobulin G [IgG] and Immunoglobulin M [IgM]) to Factor IX (FIX)
Binding antibodies (IgG and IgM) to FIX was determined using validated enzyme-linked immunosorbent assays (ELISAs) employing polyclonal anti-human IgG and IgM antibodies. Number of participants who developed binding antibodies (IgG and IgM) combined data to FIX were reported.
Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins and rFurin
Citrated plasma was assayed for the presence of antibodies to CHO protein and rFurin, derived from cultures of un-transfected cells. Testing for binding anti-CHO protein and rFurin antibodies was done on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG antibodies. Number of participants who developed binding antibodies to CHO proteins and rFurin were reported.
Annualized Bleeding Rate (ABR) With Prophylactic Use of RIXUBIS
The ABR was defined as the total number of unique bleeding episodes by participants reported during RIXUBIS treatment for prophylaxis, divided by the RIXUBIS treatment duration for prophylaxis and multiplied by 365.25. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not be associated to a trauma event (spontaneous bleeding). Bleeding occurring at multiple locations related to the same injury (e.g., knee and ankle bleed following a fall) was counted as a single bleeding episode.
Rate of Success of RIXUBIS for Treatment of Bleeding Episodes
The success of RIXUBIS for treatment of bleeding episodes was defined by grouping the categories of "Excellent"/"Good" of the corresponding hemostatic effectiveness ratings of a 4 point Likert scale ("Excellent", "Good", "Moderate" and "None") by the participants/legally authorized representative (LAR) (participants less than (<) 12 years: LAR, participants greater than or equal to (>=) 12 years: self-assessment) for treatments given at home, or by the investigator for treatments given in the hospital/clinic. The rate of success of RIXUBIS for treatment of bleeding episodes was defined as: The number of successful bleeding episodes/total number of bleeding episodes where the treatment of the bleeding was rated *100. Rate of success of RIXUBIS for treatment of bleeding episodes, 95% confidence interval (CIs) was calculated using the exact Binomial CI (Clopper-Pearson method).
Full Information
NCT ID
NCT03565237
First Posted
June 11, 2018
Last Updated
August 4, 2022
Sponsor
Baxalta now part of Shire
Collaborators
Baxalta Innovations GmbH, now part of Shire
1. Study Identification
Unique Protocol Identification Number
NCT03565237
Brief Title
RIXUBIS PMS India (RIXUBIS PMS)
Official Title
Phase IV Multi-Center, Prospective, Interventional, Post-Marketing Study in Hemophilia B Patients in India Receiving RIXUBIS as On-demand or Prophylaxis Under Standard Clinical Practice
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
December 7, 2018 (Actual)
Primary Completion Date
August 11, 2021 (Actual)
Study Completion Date
August 11, 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
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to characterize the safety and describe the effectiveness of RIXUBIS in routine clinical practice.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All Study Participants
Arm Type
Experimental
Arm Description
Study participants with Hemophilia B in India receiving Rixubis
Intervention Type
Biological
Intervention Name(s)
RIXUBIS: On-Demand
Other Intervention Name(s)
BAX326, Recombinant Factor IX, rFIX, Coagulation Factor IX [Recombinant], rFactor IX, BAX 326
Intervention Description
RIXUBIS used under standard clinical practice in India: On-Demand treatment.
Intervention Type
Biological
Intervention Name(s)
RIXUBIS: Prophylaxis
Other Intervention Name(s)
BAX326, Recombinant Factor IX, rFIX, Coagulation Factor IX [Recombinant], rFactor IX, BAX 326
Intervention Description
RIXUBIS used under standard clinical practice in India: Prophylaxis treatment.
Primary Outcome Measure Information:
Title
Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) Related to RIXUBIS
Description
TEAE was defined as any event not presented prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. A SAE was defined as any untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, life-threatening, required in-patient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event that was not immediately life-threatening or resulted in death or required hospitalization but jeopardize the participant or required medical or surgical intervention to prevent any of the above outcomes. Relatedness to study drug was based on physician discretion. Number of participants with serious TEAEs related to RIXUBIS were reported.
Time Frame
From start of study drug administration up to End of treatment (EOT) (up to 6 months)
Secondary Outcome Measure Information:
Title
Number of Participants With TEAEs Related to RIXUBIS
Description
TEAE was defined as any event not presented prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. Relatedness to study drug was based on physician discretion. Number of participants with TEAEs related to RIXUBIS were reported.
Time Frame
From start of study drug administration up to EOT (up to 6 months)
Title
Number of Participants With Clinically Significant Laboratory Abnormalities
Description
Clinical laboratory evaluations included clinical chemistry (biochemistry and endocrinology), hematology and urinalysis. Any change in clinical laboratory abnormalities which were deemed clinically significant by the investigator were recorded as TEAEs (defined as any event not presented prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments).
Time Frame
From start of study drug administration up to EOT (up to 6 months)
Title
Number of Participants Who Developed Binding Antibodies (Immunoglobulin G [IgG] and Immunoglobulin M [IgM]) to Factor IX (FIX)
Description
Binding antibodies (IgG and IgM) to FIX was determined using validated enzyme-linked immunosorbent assays (ELISAs) employing polyclonal anti-human IgG and IgM antibodies. Number of participants who developed binding antibodies (IgG and IgM) combined data to FIX were reported.
Time Frame
From start of study drug administration up to EOT (up to 6 months)
Title
Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins and rFurin
Description
Citrated plasma was assayed for the presence of antibodies to CHO protein and rFurin, derived from cultures of un-transfected cells. Testing for binding anti-CHO protein and rFurin antibodies was done on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG antibodies. Number of participants who developed binding antibodies to CHO proteins and rFurin were reported.
Time Frame
From start of study drug administration up to EOT (up to 6 months)
Title
Annualized Bleeding Rate (ABR) With Prophylactic Use of RIXUBIS
Description
The ABR was defined as the total number of unique bleeding episodes by participants reported during RIXUBIS treatment for prophylaxis, divided by the RIXUBIS treatment duration for prophylaxis and multiplied by 365.25. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not be associated to a trauma event (spontaneous bleeding). Bleeding occurring at multiple locations related to the same injury (e.g., knee and ankle bleed following a fall) was counted as a single bleeding episode.
Time Frame
From start of study drug administration up to EOT (up to 6 months)
Title
Rate of Success of RIXUBIS for Treatment of Bleeding Episodes
Description
The success of RIXUBIS for treatment of bleeding episodes was defined by grouping the categories of "Excellent"/"Good" of the corresponding hemostatic effectiveness ratings of a 4 point Likert scale ("Excellent", "Good", "Moderate" and "None") by the participants/legally authorized representative (LAR) (participants less than (<) 12 years: LAR, participants greater than or equal to (>=) 12 years: self-assessment) for treatments given at home, or by the investigator for treatments given in the hospital/clinic. The rate of success of RIXUBIS for treatment of bleeding episodes was defined as: The number of successful bleeding episodes/total number of bleeding episodes where the treatment of the bleeding was rated *100. Rate of success of RIXUBIS for treatment of bleeding episodes, 95% confidence interval (CIs) was calculated using the exact Binomial CI (Clopper-Pearson method).
Time Frame
From screening up to EOT (up to 6 months)
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
The participant or legally authorized representative (in case of study participants <18 years of age) gave written informed consent to participate in the study.
Participant has hemophilia B.
Participant is defined as previously-treated patient (PTP):
Participant aged ≥ 6 years that has been previously treated with plasma-derived and/or recombinant factor IX (FIX) concentrate(s) for a minimum of 150 exposure days (EDs).
Participant aged < 6 years that has been previously treated with plasma-derived and/or recombinant FIX concentrate(s) for a minimum of 50 EDs.
Participant has no evidence of a history of FIX inhibitors.
Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
Participant is hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer will be confirmed by polymerase chain reaction (PCR)), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
The participant is willing and able to comply with the requirements of the protocol.
Exclusion Criteria
Participant has known hypersensitivity or presence of any contraindication to RIXUBIS or its excipients including hamster protein.
Participant has evidence of an ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
Participant has a history of FIX inhibitors with a titer ≥ 0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay, employed in the respective local laboratory) at any time prior to screening.
Participant has a detectable FIX inhibitor at screening, with a titer ≥ 0.6 BU as determined by the Nijmegen modification of the Bethesda assay in the central laboratory.
Participant has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4 hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.
Participant has severe chronic hepatic dysfunction [eg, ≥ 5 times upper limit of normal alanine aminotransferase (ALT), as confirmed by central laboratory at screening, or a documented INR > 1.5].
Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia B.
Participant's platelet count is < 100,000/mL.
Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant's safety or compliance.
Participant is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or α-interferon) other than antiretroviral chemotherapy.
Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
Participant is a family member or employee of the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Sahyadri Super Speciality Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411004
Country
India
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b5fc64db2bf003ab45e07
Description
To obtain more information on the study, click here/on this link
Learn more about this trial
RIXUBIS PMS India (RIXUBIS PMS)
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