Clinical Trial Results:
A prospective, observational long-term follow-up trial of kidney transplant patients treated with imlifidase or plasma exchange after an active/chronic active antibody-mediated rejection episode
Summary
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EudraCT number |
2020-004777-49 |
Trial protocol |
FR AT DE |
Global end of trial date |
30 Mar 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Mar 2025
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First version publication date |
12 Mar 2025
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Other versions |
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 |
20-HMedIdeS-18
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04711850 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Hansa Biopharma AB
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Sponsor organisation address |
Scheelevägen 22, Lund, Sweden, 223 63
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Public contact |
Clinical Operation Department, Hansa Biopharma AB, +46 046165670, info@hansabiopharma.com
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Scientific contact |
Clinical Operation Department, Hansa Biopharma AB, +46 046165670, info@hansabiopharma.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 |
22 Nov 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Mar 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Mar 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of this trial is to evaluate kidney graft survival in subjects that have been treated with imlifidase or plasma exchange in association with AMR in trial 16-HMedIdeS-12 (referred to as the feeder trial).
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Protection of trial subjects |
No treatment was administered during this follow-up study. Administration of imlifidase was done during the feeder trial 16-HMedIdeS-12.
Details of the goals of the research and the risk and benefits of the trial protocol were reviewed with each potential trial subject.
Physicians expert in the care of patients with AMR were responsible for the patients' care at each site.
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Background therapy |
N/A this is a long-term follow-up study. | ||
Evidence for comparator |
N/A this is a long-term follow-up study. | ||
Actual start date of recruitment |
20 Jan 2021
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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 |
France: 10
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Country: Number of subjects enrolled |
Germany: 4
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Country: Number of subjects enrolled |
Austria: 4
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Worldwide total number of subjects |
18
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EEA total number of subjects |
18
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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) |
15
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited between 20-JAN-2021 and 11-NOV-2022 | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
All 18 patients who were screened were enrolled in the trial. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Blinding implementation details |
N/A
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Imlifidase | ||||||||||||||||||||||||
Arm description |
Patients in this arm received imlifidase in the feeder study 16-HMedIdeS-12 | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Imlifidase
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Investigational medicinal product code |
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Other name |
IdeS, IgG endopeptidase
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Imlifidase was not administered in this long-term follow-up trial.
Subjects randomized to imlifidase treatment in the feeder study 16-HMedIdeS-12 received one intravenous dose of imlifidase, 0.25 mg/kg, administered over 15 minutes.
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Arm title
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PLEX | ||||||||||||||||||||||||
Arm description |
Subjects randomized to plasma exchange (PLEX) treatment in the feeder study 16-HMedIdes-12 received 5-10 sessions of PLEX, as judged by the investigator. Immunoadsorption (IA) could replace PE, at the discretion of the investigator. | ||||||||||||||||||||||||
Arm type |
PLEX | ||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Imlifidase
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Reporting group description |
Patients in this arm received imlifidase in the feeder study 16-HMedIdeS-12 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PLEX
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Reporting group description |
Subjects randomized to plasma exchange (PLEX) treatment in the feeder study 16-HMedIdes-12 received 5-10 sessions of PLEX, as judged by the investigator. Immunoadsorption (IA) could replace PE, at the discretion of the investigator. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Imlifidase
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Reporting group description |
Patients in this arm received imlifidase in the feeder study 16-HMedIdeS-12 | ||
Reporting group title |
PLEX
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Reporting group description |
Subjects randomized to plasma exchange (PLEX) treatment in the feeder study 16-HMedIdes-12 received 5-10 sessions of PLEX, as judged by the investigator. Immunoadsorption (IA) could replace PE, at the discretion of the investigator. |
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End point title |
Overall graft survival at Year 3 [1] | ||||||||||||
End point description |
Graft survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to graft loss.
Graft loss is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy.
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End point type |
Primary
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End point timeframe |
Three (3) years after start of AMR treatment in feeder trial 16-HMedIdeS-12.
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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: Due to early termination of the study a large proportion of patients were censored. |
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Notes [2] - Due to the early termination of the trial a large proportion of patients were censored prior to Y3. [3] - Due to the early termination of the trial a large proportion of patients were censored prior to Y3. |
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No statistical analyses for this end point |
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End point title |
Overall graft survival at Year 1 and Year 2 | |||||||||||||||
End point description |
Graft survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to graft loss.
Graft loss is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy.
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End point type |
Secondary
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End point timeframe |
Up to 2 years after start of AMR treatment in the feeder trial (16-HMedIdes-12).
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Notes [4] - Due to the early termination of the trial a large proportion of patients were censored prior to Y2. [5] - Due to the early termination of the trial a large proportion of patients were censored prior to Y2. |
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No statistical analyses for this end point |
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End point title |
Patient survival at Year 3 | ||||||||||||
End point description |
Overall patient survival is defined as time from start of AMR treatment in feeder study (16-HMedIdeS-12) to death for any cause.
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End point type |
Secondary
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End point timeframe |
Up to 3 years after start of AMR treatment in the feeder study (16-HMedIdeS-12).
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Notes [6] - Due to the early termination of the trial a large proportion of patients were censored prior to Y3. [7] - Due to the early termination of the trial a large proportion of patients were censored prior to Y3. |
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No statistical analyses for this end point |
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End point title |
Kidney function as evaluated by eGFR | |||||||||||||||||||||
End point description |
Estimated glomerular filtration rate (eGFR) was calculated as described by the Modification of Diet in Renal Disease Study (MDRD) equation. eGFR is a measure of kidney function.
eGFR for a kidney with normal function is 90 mL/min/1.72m2.
Kidney disease is characterised by a decreased eGFR value.
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End point type |
Secondary
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End point timeframe |
Up to 3 years after start of AMR treatment in the feeder study (16-HMedIdes-12)
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Notes [8] - 8 patients Y1, 3 patients Y2, 1 patient Y3 due to early termination of trial. [9] - 4 patients Y1, 1 patient Y2, 0 patients Y3 due to early termination of trial. |
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No statistical analyses for this end point |
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End point title |
Kidney function as evaluated by creatinine | |||||||||||||||||||||
End point description |
The creatinine in blood is a measure of kidney function.
Kidney disease is characterized by an increased creatinine level.
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End point type |
Secondary
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End point timeframe |
Up to 3 years after start of AMR treatment in the feeder study (16-HMedIdes-12).
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Notes [10] - 8 patients Y1, 3 patients Y2, 1 patient Y3 due to early termination of trial. [11] - 4 patients Y1, 1 patient Y2, 0 patients Y3 due to early termination of trial. |
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No statistical analyses for this end point |
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End point title |
AMR episodes (presumed or biopsy proven) | ||||||||||||
End point description |
Information about AMR episodes was collected according to Banff 2017 or later classification.
For-cause biopsies together with contemporaneous local donor specific antibodies (DSA) analyses, kidney function parameters (creatinine, albumin/creatinine ratio in
urine) and treatments (e.g. plasma exchange and IVIg) were collected to assess the rejection episodes.
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End point type |
Secondary
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End point timeframe |
Up to 3 years after start of AMR treatment in the feeder study (16-HMedIdeS-12).
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Notes [12] - Due to early termination of the trial a large proportion of patients were censored prior to Y3. [13] - Due to early termination of the trial a large proportion of patients were censored prior to Y3. |
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No statistical analyses for this end point |
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End point title |
Rejection episodes other than AMR (presumed or biopsy proven) | ||||||||||||
End point description |
Information about rejection episodes were collected according to Banff 2017 or later classification.
For-cause biopsies together with contemporaneous local donor specific antibodies (DSA) analyses, kidney function parameters (creatinine, albumin/creatinine ratio in
urine) and treatments (e.g. plasma exchange and IVIg) were collected to assess the rejection episodes.
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End point type |
Secondary
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End point timeframe |
Up to 3 years after AMR treatment in the feeder study (16-HMedIdeS-12).
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Notes [14] - Due to early termination of the trial a large proportion of patients were censored prior to Y3. [15] - Due to early termination of the trial a large proportion of patients were censored prior to Y3. |
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No statistical analyses for this end point |
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End point title |
Levels of donor specific antibodies (DSA) | ||||||||||||||||||||||||
End point description |
DSA levels were measured using single antigen bead human leukocyte antigen (SAB-HLA) assay.
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End point type |
Secondary
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End point timeframe |
Up to 3 years after start of AMR treatment in the feeder study (16-HMedIdeS-12).
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Notes [16] - 10 pre-dose in 16-HMedIdeS-12, 8 patients Y1, 3 patients Y2, 1 patient Y3 due to early termination [17] - 5 pre-dose in 16-HMedIdeS-12, 2 patients Y1, 1 patients Y2, 0 patients Y3 due to early termination |
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No statistical analyses for this end point |
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End point title |
Levels of anti-drug IgG antibodies [18] | ||||||||||||||
End point description |
The immunogenicity of imlifidase was assessed by measuring ADA levels.
Only patients exposed to imlifidase were assessed for ADA.
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End point type |
Secondary
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End point timeframe |
Up to 3 years after start of AMR treatment in the feeder study (16-HMedIdeS-12).
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Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The patients in the PLEX arm were not exposed to imlifidase. Hence N/A to measure ADA for this group. |
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Notes [19] - 8 patients at Y1, 3 patients at Y2, 1 patient at Y3 due to early termination of the trial |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
From inclusion until end of study (Year 3).
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Adverse event reporting additional description |
Only AEs related to trial procedure or related to IMP administered in feeder trial were to be collected.
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Assessment type |
Systematic | |||||||||||||||
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 |
Imlifidase treatment in the feeder study (16-HMedIdeS-12)
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Reporting group description |
All patients treated with imlifidase in the feeder study 16-HMedIdes-12. No treatment was administered in this long-term follow-up trial. | |||||||||||||||
Reporting group title |
PLEX treatment in the feeder study (16-HMedIdeS-12)
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Reporting group description |
All patients treated with PLEX in the feeder study. No treatment was administered in this long-term follow-up study. | |||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Only AEs related to trial procedure or related to IMP administered in feeder trial were to be collected. No such events were reported. |
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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. | |||
Early termination leading to small number of subjects analysed. |