Clinical Trial Results:
A Single Country, Multicenter, Open-Label and Non-Randomised Clinical Trial With Moroctocog Alfa (AF-CC) Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients With Moderate and Severe Hemophilia A for a Duration of 8 Weeks
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Summary
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EudraCT number |
2020-004570-21 |
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 |
21 Mar 2021
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First version publication date |
21 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 |
B1831097
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04396639 | ||
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 8007181021, 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 |
06 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 moroctocog alfa (AF-CC) when administered for prophylaxis with
respect to incidence of factor VIII (FVIII) inhibitor development.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jan 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: 50
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Worldwide total number of subjects |
50
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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) |
4
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Adults (18-64 years) |
46
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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 |
In this study, subjects aged greater than or equal to (>=) 12 years to less than or equal to (<=) 65 years, with moderate or severe hemophilia A (circulating factor VIII [FVIII: C] <=5 percent [%]), who previously had at least 50 exposure days to FVIII-containing products were enrolled. | ||||||||||||||
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Pre-assignment
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Screening details |
This study was conducted in 4 sites in India from 25-Jan-2020 to 24-Sep-2020. This study used an Institutional Review Board/Ethics Committee. | ||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Moroctocog Alfa (AF-CC) | ||||||||||||||
Arm description |
Moroctocog alfa was administered prophylactically at a dose of 30 international unit per kilogram (IU/kg), 3 times weekly in accordance with local product document and with procedures provided by physicians. For on-demand treatment, the amount administered and the frequency of administration of moroctocog alfa was tailored to the clinical effectiveness in individual subjects by their physicians. Subjects continued participating in the study until 24 exposure days or until 8 weeks of treatment (whichever occurred first). Post treatment subjects were followed up to 28 days. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Moroctocog 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 |
Moroctocog alfa was administered prophylactically at a dose of 30 IU/kg, 3 times weekly until 24 exposure days or until 8 weeks of treatment.
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Baseline characteristics reporting groups
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Reporting group title |
Moroctocog Alfa (AF-CC)
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Reporting group description |
Moroctocog alfa was administered prophylactically at a dose of 30 international unit per kilogram (IU/kg), 3 times weekly in accordance with local product document and with procedures provided by physicians. For on-demand treatment, the amount administered and the frequency of administration of moroctocog alfa was tailored to the clinical effectiveness in individual subjects by their physicians. Subjects continued participating in the study until 24 exposure days or until 8 weeks of treatment (whichever occurred first). Post treatment subjects were followed up to 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Moroctocog Alfa (AF-CC)
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Reporting group description |
Moroctocog alfa was administered prophylactically at a dose of 30 international unit per kilogram (IU/kg), 3 times weekly in accordance with local product document and with procedures provided by physicians. For on-demand treatment, the amount administered and the frequency of administration of moroctocog alfa was tailored to the clinical effectiveness in individual subjects by their physicians. Subjects continued participating in the study until 24 exposure days or until 8 weeks of treatment (whichever occurred first). Post treatment subjects were followed up to 28 days. | ||
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End point title |
Percentage of Subjects who Developed Factor VIII (FVIII) Inhibitors [1] | ||||||||
End point description |
FVIII inhibitor development was defined as an inhibitor titer of >=0.6 Bethesda units per milliliter (BU)/mL as confirmed by the central laboratory during the course of the study. Safety analysis set included all subjects who received at least 1 dose of moroctocog alfa.
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End point type |
Primary
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End point timeframe |
24 exposure days or 8 weeks of treatment during the study (whichever occurred first)
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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 reported 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 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 after last dose that were absent before treatment or that worsened relative to pretreatment state. In this endpoint all AEs are reported. Safety analysis set included all subjects who received at least 1 dose of moroctocog alfa.
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End point type |
Secondary
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End point timeframe |
Day 1 up to 28 days after last dose of study drug (approximately maximum up to 12 Weeks)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Treatment Emergent Serious Adverse Events (SAEs) | ||||||
End point description |
SAEs: an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; inpatient hospitalisation or prolongation of existing hospitalisation; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Safety analysis set included all subjects who received at least 1 dose of moroctocog alfa.
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End point type |
Secondary
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End point timeframe |
Day 1 up to 28 days after last dose of study drug (approximately maximum up to 12 Weeks)
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| No statistical analyses for this end point | |||||||
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End point title |
Mean Annualised Bleeding Rate (ABR) During Prophylaxis | ||||||||
End point description |
Subjects who had bleeding episode, ABR was derived by the following formula: ABR = number of bleeds per treatment interval duration per 365.25. Subjects who did not have bleeding episodes for them ABR was 0. In this endpoint, mean ABR was reported considering all the subjects (with bleeding episodes and without bleeding episodes). Safety analysis set included all subjects who received at least 1 dose of moroctocog alfa.
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End point type |
Secondary
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End point timeframe |
24 exposure days or 8 weeks of treatment during the study (whichever occurred first)
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Annualised Total Factor Consumption (TFC) | ||||||||
End point description |
The total amount in international units (IU) infused for each infusion recorded were summed to calculate the TFC for each subject during the treatment interval duration (up to 8 weeks of treatment, or sooner, once 24 exposure days are achieved). The annualised TFC of moroctocog alfa was derived for each subject by using the following formula: Annualised TFC = (TFC / treatment interval duration)*365.25. Safety analysis set included all subjects who received at least 1 dose of moroctocog alfa.
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End point type |
Secondary
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End point timeframe |
24 exposure days or 8 weeks of treatment during the study (whichever occurred first)
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Annualised Total Factor Consumption (TFC) by Weight | ||||||||
End point description |
The total amount in IU infused for each infusion recorded was summed to calculate the TFC for each subjects during the treatment interval duration (up to 8 weeks of treatment, or sooner, once 24 exposure days are achieved). The annualised TFC of moroctocog alfa was derived for each subject by using the following formula: Annualised TFC = (TFC / treatment interval duration)*365.25. To calculate the annualised TFC per weight, the most recently recorded weight measurement was used. Safety analysis set included all subjects who received at least 1 dose of moroctocog alfa.
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End point type |
Secondary
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End point timeframe |
24 exposure days or 8 weeks of treatment during the study (whichever occurred first)
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean of Number of Moroctocog Alfa (AF-CC) Infusions Used to Treat Each New Bleed | ||||||||
End point description |
Number of moroctocog 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). If there was more than one bleed location (e.g., ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence. Safety analysis set included all subjects who received at least 1 dose of moroctocog alfa. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
24 exposure days or 8 weeks of treatment during the study (whichever occurred first)
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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 |
Day 1 up to 28 days after last dose of study drug (approximately maximum up to 12 Weeks)
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Adverse event reporting additional description |
Same event may appear as AE and SAEs, what is presented are distinct events. Event may be categorised as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. Safety analysis set included all subjects who received at least 1 dose of moroctocog alfa.
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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 |
23.1
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Reporting groups
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Reporting group title |
Moroctocog Alfa (AF-CC)
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Reporting group description |
Moroctocog alfa was administered prophylactically at a dose of 30 IU/kg, 3 times weekly in accordance with local product document and with procedures provided by physicians. For on-demand treatment, the amount administered and the frequency of administration of moroctocog alfa was tailored to the clinical effectiveness in individual subjects by their physicians. Subjects continued participating in the study until 24 exposure days or until 8 weeks of treatment (whichever occurred first). Post treatment subjects were followed up to 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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16 Sep 2019 |
In order to simplify dosing and minimizing potential waste a dosing variance of +/-5 IU/kg was permitted. |
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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 | |||
