HEMOPHILIA BPhase 4NCT02336178
Safety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China
A Phase 4 study testing Benefix in people with HEMOPHILIA B, run by Pfizer at 16 sites in China.
Trial summary
The purpose of this post-approval study is to evaluate the safety and efficacy of Benefix in subjects with hemophilia B in usual care settings in China. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HEMOPHILIA B
- What is being tested?
- Benefix
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 16 sitesChina
- Study dates
- Jan 2015to Aug 2016
- Phase
- Phase 4
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male and/or female subjects with hemophilia B.
- Subjects/parents/legal representatives must be able to comply with study procedures (informed consent/assent process, clinical visits, reporting of infusion and bleed data, reporting of adverse events, etc)
Who cannot join
- Presence of any other bleeding disorder in addition to hemophilia B. Subjects with a past history of, or current factor IX inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer greater than the laboratory's normal range or ≥0.6 Bethesda Unit (BU)/mL.
- Subjects with known hypersensitivity to the active substance or to any of the excipients of BeneFIX.
- Subjects with a known hypersensitivity to Chinese Hamster Ovary cell proteins.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
China16 sites
Hematology Department,Beijing Children's Hospital, Capital Medical University
Beijing, 100045
Xiangya Hospital of Centre-South University
Changsha, Hunan, 410008
Chengdu Women's and Children's Central Hospital
Chengdu, Sichuan, 610073
Children's Hospital of Chongqing Medical University
Chongqing, 400014
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, 550004
Blood Center of Shandong Province
Jinan, Shandong, 250014
Department of Hematology,The First Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, 650032
Department of Hematology,Jiangxi Provincial People's Hospital
Nanchang, Jiangxi, 330006
Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine/Hematology Department
Shanghai, Shanghai Municipality, 200025
Department of Hematology,The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006
Shanxi Medical University Second Hospital
Taiyuan, Shanxi, 030001
Blood Diseases Hospital, Chinese Academy of Medical Science (Institute of Hematology)
Tianjin, Tianjin Municipality, 300020
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, 430030
Department of Hematology,The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221006
Henan Provincial People's Hospital
Zhengzhou, Henan, 450003
About this study
Official title: An Open-label, Single-arm, Post-authorization Pragmatic Clinical Trial On The Safety And Efficacy Of Benefix (Nonacog Alfa, Recombinant Factor Ix) In Subjects With Hemophilia B In Usual Care Settings In China
The purpose of this post-approval study is to evaluate the safety and efficacy of Benefix in subjects with hemophilia B in usual care settings in China.
Read the detailed description
The purpose of this post-approval study is to provide supplementary information relating to the use of BeneFIX in Chinese subjects with hemophilia B, especially on the safety and efficacy in different populations of Chinese hemophilia B patients, in particular in pediatric patients <6 years of age, pediatric patients ≥6 to ≤12 years of age, Previously Untreated Patients (PUPs) , subjects receiving prophylaxis treatment after enrollment in the study, and severe patients (FIX activity <1%).
- Conditions
- HEMOPHILIA B
- Being tested
- Benefix
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BenefixDrug
Subjects will be treated by the investigator according to usual care in China and in accord with the China BeneFIX Package Insert.
The treatment duration is approximately 6 months (±7 days) or approximately 50 Exposure Days (EDs) (±5 EDs) (see protocol definition on EDs) whichever occurs first.
| Study group | Role | What they receive |
|---|---|---|
| Benefix | Experimental | This is a single arm study. Subjects will be treated with Benefix by the investigator according to usual care in China and in accord with the China BeneFIX Package Insert. Receives: Drug: Benefix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Developed Factor IX Inhibitor
Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer >=0.6 Bethesda Unit (BU)/mL.
Measured: Up to 6 months
Number of Participants With Allergic Reactions
FIX product allergy was defined as a hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgments.
Measured: Up to 6 months
Number of Participants With Thrombotic Events
Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications.
Measured: Up to 6 months
Secondary outcomes (11)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causality with the treatment or usage. A serious adverse event (SAE) was any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.
Measured: Up to 7 months (28 calendar days after end of 6-month or 50-exposure day study treatment)
Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period
For prophylaxis period, annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in prophylaxis period / (number of days in prophylaxis period/365.25). A prophylaxis period was defined as time from first prophylaxis infusion through 6 calendar days after the day of last prophylaxis infusion, or the day of study conclusion visit, whichever was earlier. A break in the prophylaxis period was any period of 28 days or longer in which no prophylaxis infusions were given. For a prophylaxis regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >=14 days.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX
The prophylaxis infusion time, bleed start time and bleed type (etiology) were used to determine the number of spontaneous, non-traumatic breakthrough bleeds that occurred <=48 hours after a prophylaxis infusion. If there was more than 1 bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period
For on-demand period, the annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in on-demand period / (number of days in on-demand period/365.25). The on-demand period was defined as the entire time of enrollment in the study (ie, from the date of the enrollment visit through the day before the Final/Early Termination visit) except time in any prophylaxis period. The breaks in the prophylaxis period were considered on-demand periods. For an on-demand regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >= 14 days.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response
Response was assessed using 4-point On-Demand Hemostasis Efficacy Rating Scale. Excellent means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered; good means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode, or definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered; moderate means probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; no response means no improvement between infusions or during the 24 hour interval following an infusion, or condition worsens. Both first infusions and follow-up infusions were included.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Number of BeneFIX Infusions to Treat Each New Bleed
The number of BeneFIX infusions administered to treat each new bleed was calculated by adding the on-demand initial treatment and any on-demand follow-up treatments for the same bleed. If there was more than one bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Average Infusion Dose and Total Factor IX Consumption in On-demand Setting
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Average Infusion Dose and Total Factor IX Consumption in Recovery Setting
The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting
Less than expected therapeutic effect (LETE) in the on-demand setting was defined as 2 successive "no response" ratings recorded after 2 successive BeneFIX drug infusions, respectively.
Measured: Up to 6 months or 50 exposure days whichever occurred first
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting
Less than expected therapeutic effect (LETE) in the prophylaxis setting was defined as occurrence of any spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of BeneFIX (which was not used to treat a bleed).
Measured: Up to 6 months or 50 exposure days whichever occurred first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2015 (estimated)
- Study startJan 2015
- Primary completionJul 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HEMOPHILIA BStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02336178
- Sponsor's protocol ID
- B1821052
- Other IDs
- 2016-000765-22, 2016
- Status last verified
- Mar 2017
- First submitted
- 16 Dec 2014
- Last updated
- 4 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Yang R, Wu R, Sun J, Sun F, Rupon J, Huard F, Korth-Bradley JM, Xu L, Luo B, Liu YC, Rendo P. First open-label, single-arm, prospective study of real-world use of FIX replacement therapy in a predominantly pediatric hemophilia B population in China. Medicine (Baltimore). 2021 May 28;100(21):e26077. doi: 10.1097/MD.0000000000026077.
PubMed 34032739
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-arm, Post-authorization Pragmatic Clinical Trial On The Safety And Efficacy Of Benefix (Nonacog Alfa, Recombinant Factor Ix) In Subjects With Hemophilia B In Usual Care Settings In China
- ClinicalTrials.gov ID
- NCT02336178
- Acronym / sponsor ID
- B1821052
- Conditions
- HEMOPHILIA B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Jan 2015 (actual)
- Primary completion
- Jul 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 12 Jan 2015 (estimated)
- Results
- Posted 4 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this post-approval study is to evaluate the safety and efficacy of Benefix in subjects with hemophilia B in usual care settings in China.
Detailed description
The purpose of this post-approval study is to provide supplementary information relating to the use of BeneFIX in Chinese subjects with hemophilia B, especially on the safety and efficacy in different populations of Chinese hemophilia B patients, in particular in pediatric patients <6 years of age, pediatric patients ≥6 to ≤12 years of age, Previously Untreated Patients (PUPs) , subjects receiving prophylaxis treatment after enrollment in the study, and severe patients (FIX activity <1%).
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Benefix | Experimental | Drug: BenefixThis is a single arm study. Subjects will be treated with Benefix by the investigator according to usual care in China and in accord with the China BeneFIX Package Insert. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Male and/or female subjects with hemophilia B.
- Subjects/parents/legal representatives must be able to comply with study procedures (informed consent/assent process, clinical visits, reporting of infusion and bleed data, reporting of adverse events, etc)
Key exclusion criteria (3 listed)
- Presence of any other bleeding disorder in addition to hemophilia B. Subjects with a past history of, or current factor IX inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer greater than the laboratory's normal range or ≥0.6 Bethesda Unit (BU)/mL.
- Subjects with known hypersensitivity to the active substance or to any of the excipients of BeneFIX.
- Subjects with a known hypersensitivity to Chinese Hamster Ovary cell proteins.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BenefixSubjects will be treated by the investigator according to usual care in China and in accord with the China BeneFIX Package Insert. The treatment duration is approximately 6 months (±7 days) or approximately 50 Exposure Days (EDs) (±5 EDs) (see protocol definition on EDs) whichever occurs first. | Drug | Benefix |
Primary outcome
Percentage of Participants Who Developed Factor IX Inhibitor
Time frame: Up to 6 months
Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer >=0.6 Bethesda Unit (BU)/mL.
Number of Participants With Allergic Reactions
Time frame: Up to 6 months
FIX product allergy was defined as a hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgments.
Number of Participants With Thrombotic Events
Time frame: Up to 6 months
Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications.
11 secondary outcomes
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to 7 months (28 calendar days after end of 6-month or 50-exposure day study treatment)
Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Number of BeneFIX Infusions to Treat Each New Bleed
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Average Infusion Dose and Total Factor IX Consumption in On-demand Setting
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Average Infusion Dose and Total Factor IX Consumption in Recovery Setting
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34032739Yang R, Wu R, Sun J, Sun F, Rupon J, Huard F, Korth-Bradley JM, Xu L, Luo B, Liu YC, Rendo P. First open-label, single-arm, prospective study of real-world use of FIX replacement therapy in a predominantly pediatric hemophilia B population in China. Medicine (Baltimore). 2021 May 28;100(21):e26077. doi: 10.1097/MD.0000000000026077.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Benefix in people with HEMOPHILIA B, run by Pfizer at 16 sites in China.
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 2 inclusion and 3 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 4 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 4 May 2017). 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?
Percentage of Participants Who Developed Factor IX Inhibitor (time frame: Up to 6 months). The study lists 3 primary outcomes in all. 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 NCT02336178, which also lists 1 linked publication.
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 4 May 2017.