RIXUBIS PMS India (RIXUBIS PMS)

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

The purpose of this study is to characterize the safety and describe the effectiveness of RIXUBIS in routine clinical practice.

Study Overview

• Status: Completed
• Conditions: Hemophilia B
• Intervention / Treatment: Biological: RIXUBIS: On-Demand; Biological: RIXUBIS: Prophylaxis

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. The participant or legally authorized representative (in case of study participants <18 years of age) gave written informed consent to participate in the study.
2. Participant has hemophilia B.

3. 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.
4. Participant has no evidence of a history of FIX inhibitors.
5. 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.
6. 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.
7. The participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria

1. Participant has known hypersensitivity or presence of any contraindication to RIXUBIS or its excipients including hamster protein.
2. Participant has evidence of an ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
3. 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.
4. 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.
5. 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.
6. 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].
7. Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
8. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia B.
9. Participant's platelet count is < 100,000/mL.
10. 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.
11. 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.
12. 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.
13. Participant is a family member or employee of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All Study Participants; Study participants with Hemophilia B in India receiving Rixubis

Biological: RIXUBIS: On-Demand; RIXUBIS used under standard clinical practice in India: On-Demand treatment.; Other Names: BAX326; Coagulation Factor IX [Recombinant]; rFIX; BAX 326; Recombinant Factor IX; rFactor IX; Biological: RIXUBIS: Prophylaxis; RIXUBIS used under standard clinical practice in India: Prophylaxis treatment.; Other Names: BAX326; Coagulation Factor IX [Recombinant]; rFIX; BAX 326; Recombinant Factor IX; rFactor IX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From start of study drug administration up to End of treatment (EOT) (up to 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From start of study drug administration up to EOT (up to 6 months)
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).	From start of study drug administration up to EOT (up to 6 months)
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.	From start of study drug administration up to EOT (up to 6 months)
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.	From start of study drug administration up to EOT (up to 6 months)
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.	From start of study drug administration up to EOT (up to 6 months)
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).	From screening up to EOT (up to 6 months)

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Collaborators: Baxalta Innovations GmbH, now part of Shire

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2018
• Primary Completion (Actual): August 11, 2021
• Study Completion (Actual): August 11, 2021

Study Registration Dates

• First Submitted: June 11, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): August 30, 2022
• Last Update Submitted That Met QC Criteria: August 4, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: 251602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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