Clinical Trial Results:
Post-marketing investigation (PMI) to assess safety and efficacy of Jivi (BAY 94-9027) treatment in patients with hemophilia A
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Summary
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EudraCT number |
2018-003655-37 |
Trial protocol |
NO DK ES PL BG GR IT |
Global end of trial date |
26 Aug 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Aug 2023
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First version publication date |
11 Aug 2023
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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 |
19764
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04085458 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368
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Public contact |
Therapeutic Area Head, Bayer AG, +49 30 300139003, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, +49 30 300139003, clinical-trials-contact@bayer.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Aug 2022
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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 |
26 Aug 2022
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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 assess safety of Jivi
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent was read by and explained to all the subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Sep 2019
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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 |
Bulgaria: 3
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Country: Number of subjects enrolled |
Denmark: 7
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Country: Number of subjects enrolled |
Greece: 3
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
Norway: 4
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Country: Number of subjects enrolled |
Poland: 9
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Country: Number of subjects enrolled |
Spain: 4
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Worldwide total number of subjects |
36
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EEA total number of subjects |
36
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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) |
0
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Adults (18-64 years) |
32
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From 65 to 84 years |
4
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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 13 centers in 7 countries between 23 SEP 2019 (First subject first visit) and 26 Aug 2022 (last subject's data from the last visit were received). Bulgaria (2 centers), Denmark (1 centers), Spain (3 centers), Greece (1 center), Italy (3 centers), Norway (1 center), Poland (2 centers). | ||||||||||||||
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Pre-assignment
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Screening details |
36 subjects were screened into the study (signed informed consent form (ICF)). 4 subjects were screening failed. | ||||||||||||||
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Period 1
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Period 1 title |
Overall (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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Severe hemophilia A patients with Jivi treatment | ||||||||||||||
Arm description |
Prophylaxis regimens with every 5 days treatment (45-60 IU/kg), or every 7 days (60 IU/kg) or twice per week (40 IU/kg). | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Damoctocog alfa pegol (Jivi, BAY94-9027)
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Investigational medicinal product code |
BAY94-9027
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dosage regimens were every 5 days treatment (45-60 IU/kg), or every 7 days (60 IU/kg) or twice per week (40 IU/kg).
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Number of subjects worldwide (36) were subjects who signed informed consent form (ICF)). Number of subjects in baseline (32) were subjects who received study intervention. |
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Baseline characteristics reporting groups
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Reporting group title |
Severe hemophilia A patients with Jivi treatment
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Reporting group description |
Prophylaxis regimens with every 5 days treatment (45-60 IU/kg), or every 7 days (60 IU/kg) or twice per week (40 IU/kg). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Severe hemophilia A patients with Jivi treatment
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Reporting group description |
Prophylaxis regimens with every 5 days treatment (45-60 IU/kg), or every 7 days (60 IU/kg) or twice per week (40 IU/kg). | ||
Subject analysis set title |
Safety analysis set (SAF)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
A subject was included in the SAF if he received at least 1 infusion of study drug.
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Subject analysis set title |
Modified intent-to-treat set (mITT)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
A subject was included in the mITT if he received at least 1 infusion of study drug and had injection/bleeding data available for at least 3 months. This time period is considered the minimum observation time for a reliable annualization of the observed bleed rate.
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End point title |
FVIII inhibitor development by the Nijmegen Bethesda assay [1] | ||||||||||||||
End point description |
FVIII inhibitor testing was performed using the Nijmegen-modified Bethesda assay. A positive inhibitor result was defined as a threshold of ≥0.6 BU/mL at the central laboratory and had to be confirmed with a second blood sample. After confirmation of the positive result, the inhibitor was to be reported as an SAE. The analysis of this end point was performed on the SAF.
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End point type |
Primary
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End point timeframe |
Observed for 100 exposure days (EDs), up to 2 years.
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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: There were no subjects with a positive FVIII inhibitor measurement, therefore, there was no statistical analysis |
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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 | ||||||||||||||||||||||||
End point description |
Treatment-emergent AEs were defined as those that started after the first dose of study drug and up to 7 days after the last dose. The analysis of this end point was performed on the SAF.
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End point type |
Secondary
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End point timeframe |
Observed for 100 exposure days (EDs), up to 2 years.
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Development of treatment-emergent anti-PEG antibodies | ||||||||
End point description |
Anti-PEG antibody: antibody against the PEG moiety determined by enzyme-linked immunosorbent assay (ELISA). For participants with a positive result, IgM antibodies were tested.
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End point type |
Secondary
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End point timeframe |
Observed for 100 exposure days (EDs), up to 2 years.
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| No statistical analyses for this end point | |||||||||
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End point title |
Annualized bleeding rate (ABR) | ||||||||
End point description |
ABR is number of all bleeds per individual treatment period annualized to a 1-year time interval. The analysis of this end point was performed on the mITT.
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End point type |
Secondary
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End point timeframe |
Observed for 100 exposure days (EDs), up to 2 years.
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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 |
Timeframe for TEAEs: After the first study intervention up to 7 days after the end of study intervention with an average of 475 days. Timeframe for deaths (all causes): with an average of 476 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 |
25.0
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Reporting groups
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Reporting group title |
BAY94-9027 prophylaxis treatment
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Reporting group description |
The recommended starting dose was every 5 days treatment (45 IU/kg). An assessment of response to treatment will be performed at the next scheduled visit after 10-15 ED (8-10 weeks). Thereafter, participants may be assigned to different dosing regimens (every 7 days or 2x/week) or continue with every 5 days regimen, according to individual bleeding tendency and needs at investigator's discretion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 Feb 2020 |
Amendment 1 was prepared to incorporate Health Authority feedback regarding the definitions for the end of study and adverse events, assessment of body weight at additional visits, and clarification that screen failures may be re-screened once. |
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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 | |||
