Clinical Trial Results:
A Single Country, Multicenter, Open-Label and Non-Randomized Clinical Trial With Nonacog Alfa Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients With Moderately-Severe to Severe Hemophilia B for a Duration of 8 Weeks
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Summary
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EudraCT number |
2020-004430-38 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
24 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Mar 2021
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First version publication date |
17 Mar 2021
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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 |
B1821059
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.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 |
02 Nov 2020
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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 |
24 Sep 2020
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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 |
To study the safety of nonacog alfa when administered for prophylaxis with respect to incidence of factor IX (FIX) inhibitor development.
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Protection of trial subjects |
The study was conducted in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Feb 2020
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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) |
3
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Adults (18-64 years) |
22
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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 in India from 10 Feb 2020 to 24 Sep 2020. A total of 25 subjects were enrolled. | ||||||
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Pre-assignment
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Screening details |
In this study, subjects aged greater than or equal to (>=) 12 years to less than or equal to (<=) 65 years, congenital moderately-severe to severe hemophilia B (FIX activity less than or equal 2 percent) who had at least 50 exposure days (EDs) to FIX-containing products were enrolled. | ||||||
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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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Nonacog alfa | ||||||
Arm description |
Subjects received nonacog alfa intravenous (IV) injection as follows: Prophylactic treatment regimen: at a dose of 40 international unit per kilogram (IU/kg) (range 13 to 78 IU/kg) at intervals of 3 to 4 days in accordance with the local product document (LPD) guidelines until at least 16 exposure days or a period of up to 8 weeks on nonacog alfa treatment had occurred (whichever occurred first). For on demand (OD)treatment (infusions used to treat bleeding episodes) regimen nonacog alfa was administered at individual doses and frequency depending on the clinical effectiveness in individual subjects as recommended in approved LPD. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Nonacog alfa
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received nonacog alfa at a dose of 40 IU/kg (range 13 to 78 IU/kg) for up to 8 weeks or until 16 exposure days, whichever occurred first.
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nonacog alfa
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Reporting group description |
Subjects received nonacog alfa intravenous (IV) injection as follows: Prophylactic treatment regimen: at a dose of 40 international unit per kilogram (IU/kg) (range 13 to 78 IU/kg) at intervals of 3 to 4 days in accordance with the local product document (LPD) guidelines until at least 16 exposure days or a period of up to 8 weeks on nonacog alfa treatment had occurred (whichever occurred first). For on demand (OD)treatment (infusions used to treat bleeding episodes) regimen nonacog alfa was administered at individual doses and frequency depending on the clinical effectiveness in individual subjects as recommended in approved LPD. | ||
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End point title |
Percentage of Subjects who Developed Factor IX (FIX) Inhibitors [1] | ||||||||
End point description |
FIX inhibitor development was defined as an inhibitor titer >= 0.6 Bethesda units per milliliter (BU/mL) confirmed by central laboratory testing during the course of the study. Safety analysis set included all subjects who received at least one dose of nonacog alfa.
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End point type |
Primary
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End point timeframe |
At Visit 4 (any 1 day between Day 52 to Day 60)
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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 analyzed for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects With Serious Adverse Events (SAEs) and Medically Important Events (MIEs) | ||||||||||
End point description |
An AE is any untoward medical occurrence in clinical investigation subject administered a product or medical device; event need not necessarily to have a causal relationship with treatment or usage. SAEs: an AE resulting in any of following outcomes/deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. MIEs: any confirmed FIX inhibitor development (titer greater than or equal to 0.6 BU/mL confirmed by central laboratory testing), thrombotic events (any event associated with the formation of a blood clot including catheter-associated thrombi and thrombotic complications) and hypersensitivity reactions (hypersensitivity reaction to an FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator’s judgment). Safety analysis set.
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End point type |
Secondary
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End point timeframe |
Baseline up to 28 days after last dose of study drug (up to 116 days)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | ||||||
End point description |
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment emergent are events between first dose of study drug and up to 28 days (up tp 116 days) that were absent before treatment or that worsened relative to pretreatment state. Safety analysis set included all subjects who received at least one dose of nonacog alfa.
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End point type |
Secondary
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End point timeframe |
Baseline up to 28 days after last dose of study drug (up to 116 days)
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| No statistical analyses for this end point | |||||||
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End point title |
Mean Annualized Bleeding Rate (ABR) | ||||||||
End point description |
ABR: number of bleeding episodes per year. ABR for each subject = number of bleeds during treatment interval duration (TID)/(TID/365.25). Number of bleeds for each subject for ABR included all new bleeds (with unique start date and time) requiring treatment with nonacog alfa during TID. TID=date of Visit 4 (3-10 days after last dose) – date of Visit 2 (Day 1) +1. For subjects who had Visit 4 beyond 3 (+7) days after final dose due to COVID-19 pandemic, date of final dose was used in place of date of Visit 4. For discontinued subjects, date of final dose/last study visit date (whichever occurred later) was used to replace Visit 4. The overall mean ABR was calculated on all subjects from the safety analysis set who either received an on-demand infusion of Nonacog-Alfa due to a new bleed or did not had any bleed which required on-demand infusion with study drug.
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End point type |
Secondary
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End point timeframe |
Up to 88 Days
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| Notes [2] - Data not reported as no subject required and received OD treatment with study drug. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Annualized Total Factor Consumption (TFC) per Subject | ||||||||
End point description |
The TFC per subject was the sum of the total amount in international units (IU) infused for each infusion for each subject. Annualized TFC of nonacog alfa was derived for each subject by using the following formula; Annualized TFC = (TFC / treatment interval duration)*365.25. Treatment interval duration was calculated as the number of days beginning on Visit 2 (“Day 1”, provided an infusion was given) up to Visit 4 (any 1 day between Day 52 to Day 60). Safety analysis set included all subjects who received at least one dose of nonacog alfa.
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End point type |
Secondary
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End point timeframe |
Up to 88 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Annualized Total Factor Consumption (TFC) by Weight per Subject | ||||||||
End point description |
The total amount in international units (IU) infused for each infusion recorded were summed to calculate the total factor consumption for each subject. Annualized TFC = (TFC / treatment interval duration)*365.25. Treatment interval duration was calculated as the number of days beginning on Visit 2 (“Day 1”, provided an infusion was given) up to Visit 4 (any 1 day between Day 52 to Day 60). Safety analysis set included all subjects who received at least one dose of nonacog alfa. International unit per kilogram= IU/kg.
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End point type |
Secondary
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End point timeframe |
Up to 88 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Number of Nonacog Alfa Infusions Used to Treat Each Bleed | ||||||||
End point description |
Number of nonacog alfa infusions used to treat each bleed was calculated by adding the initial (on-demand) infusion to any subsequent (on-demand) infusions for the same bleed (same bleed start date/time). On demand treatment was defined as treatment used to treat a bleeding episode. Safety analysis set included all subjects who received at least one dose of nonacog alfa. Here, “Number of Subjects Analysed” signifies subjects evaluable for this end point.
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End point type |
Secondary
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End point timeframe |
Up to 88 days
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| Notes [3] - Data not reported as no subject was analysed with nonacog alfa infusion used to treat each bleed |
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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 |
Baseline up to 28 days after last dose of study drug (maximum up to 116 days)
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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 |
23.0
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Reporting groups
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Reporting group title |
Nonacog alfa
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Reporting group description |
Subjects received nonacog alfa IV injection as follows: Prophylactic treatment regimen: at a dose of 40 IU/kg (range 13 to 78 IU/kg) at intervals of 3 to 4 days in accordance with the LPD guidelines until at least 16 exposure days or a period of up to 8 weeks on nonacog alfa treatment had occurred (whichever occurred first). For on demand (OD) treatment (infusions used to treat bleeding episodes) regimen nonacog alfa was administered at individual doses and frequency depending on the clinical effectiveness in individual subjects as recommended in approved LPD. | ||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||
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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. | |||
| None reported | |||
