Clinical Trial Results:
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
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Summary
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EudraCT number |
2022-002520-13 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
11 Aug 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Aug 2022
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First version publication date |
20 Aug 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
251602
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03565237 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Baxalta Innovations GmbH
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Sponsor organisation address |
Industriestrasse 67, Vienna, Austria, 1220
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Public contact |
Study Director, Takeda, +1 866 842 5335, ClinicalTransparency@takeda.com
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Scientific contact |
Study Director, Baxalta Innovations GmbH, +1 866 842 5335, ClinicalTransparency@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Aug 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Aug 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to assess the safety of RIXUBIS based on serious adverse events (SAEs) (including factor IX [FIX] inhibitors).
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Protection of trial subjects |
This study was conducted in accordance with this protocol, the International Council for Harmonization Guideline for Good Clinical Practice E6 (ICH-GCP, April 1996), Title 21 of the US Code of Federal Regulations (US CFR), the EU Directives 2001/20/EC and 2005/28/EC, and applicable national and local regulatory requirements. In India, the study was registered with CTRI.nic.in (CTRI number: CTRI/2018/07/014754).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Dec 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
India: 25
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Worldwide total number of subjects |
25
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
5
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Adults (18-64 years) |
20
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 8 study sites in India from 07 December 2018 to 11 August 2021. | ||||||||||||||||
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Pre-assignment
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Screening details |
A total 25 participants were enrolled and received RIXUBIS treatment regimen (either on-demand or prophylaxis) based on discretion of the physician choice under standard clinical practice. No participants were enrolled in the on-demand treatment of RIXUBIS. Hence, no data collection and analysis were done during on-demand treatment of this study. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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RIXUBIS: Prophylaxis Treatment | ||||||||||||||||
Arm description |
Participants received intravenous bolus of RIXUBIS prophylaxis treatment at a maximum infusion rate of 10 milliliter (mL) per (/) minute based on discretion of the physician for up to 6 months as standard clinical practice. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
RIXUBIS
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Participants were treated with RIXUBIS intravenously after reconstitution with Sterile Water for Injection (SWFI) under standard clinical practice.
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Baseline characteristics reporting groups
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Reporting group title |
RIXUBIS: Prophylaxis Treatment
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Reporting group description |
Participants received intravenous bolus of RIXUBIS prophylaxis treatment at a maximum infusion rate of 10 milliliter (mL) per (/) minute based on discretion of the physician for up to 6 months as standard clinical practice. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
RIXUBIS: Prophylaxis Treatment
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Reporting group description |
Participants received intravenous bolus of RIXUBIS prophylaxis treatment at a maximum infusion rate of 10 milliliter (mL) per (/) minute based on discretion of the physician for up to 6 months as standard clinical practice. | ||
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End point title |
Number of Participants With Serious Treatment-emergent Adverse Events (TEAEs) Related to RIXUBIS [1] | ||||||
End point 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. SAS included all enrolled participants having received RIXUBIS at any time during the study.
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End point type |
Primary
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End point timeframe |
From start of study drug administration up to end of treatment (EOT) (up to 6 months)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analysed for this endpoint. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With TEAEs Related to RIXUBIS | ||||||
End point 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. SAS included all enrolled participants having received RIXUBIS at any time during the study.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to EOT (up to 6 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With Clinically Significant Laboratory Abnormalities | ||||||||||||
End point 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). SAS included all enrolled participants having received RIXUBIS at any time during the study.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to EOT (up to 6 months)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants Who Developed Binding Antibodies (Immunoglobulin G [IgG] and Immunoglobulin M [IgM]) to Factor IX (FIX) | ||||||
End point 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. SAS included all enrolled participants having received RIXUBIS at any time during the study.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to EOT (up to 6 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins and rFurin | ||||||||||
End point 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. SAS included all enrolled participants having received RIXUBIS at any time during the study.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to EOT (up to 6 months)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Annualized Bleeding Rate (ABR) With Prophylactic Use of RIXUBIS | ||||||||
End point 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. The EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met. Here, "number of participants analysed" refer to the participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
From start of study drug administration up to EOT (up to 6 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Rate of Success of RIXUBIS for Treatment of Bleeding Episodes | ||||||||
End point 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. The EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met. Here, "number of participants analysed" refer to the participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
From screening up to EOT (up to 6 months)
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From start of study drug administration up to EOT (up to 6 months)
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Adverse event reporting additional description |
SAS included all enrolled participants having received RIXUBIS at any time during the study.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
RIXUBIS: Prophylaxis Treatment
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Reporting group description |
Participants received intravenous bolus of RIXUBIS prophylaxis treatment at a maximum infusion rate of 10 mL/minute based on discretion of the physician for up to 6 months as standard clinical practice. | ||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| No participants were enrolled in the on-demand treatment of RIXUBIS. Hence, no data collection and analysis was done during on-demand treatment of this study. | |||
