A Prospective Observational, Long Term Follow up Study of Patients Treated With Imlifidase Prior to Kidney Transplantation
Conditions: Kidney Transplant Failure and Rejection
Sponsor: Hansa Biopharma AB

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
1 (43) 
Clinical Study Protocol  
including non-substantial Amendment 03 
A prospective, observational long-term follow up study of patients treated with 
imlifidase (IdeS) prior to kidney transplantation 
Study No.: 
17-HMedIdeS-14
Investigational Medicinal Product: 
NA  
Phase: 
Prospective, follow up study 
EudraCT Number: 
NA 
IND Number: 
128074 
Name and Address of Sponsor: 
Hansa Biopharma.AB. Box 785 
220 07 Lund 
Sweden 
This confidential document is the property of Hansa Biopharma AB. No unpublished information contained herein may be disclosed without 
prior written approval from Hansa Biopharma AB. Access to this document must be restricted to relevant parties. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
2 (43) 
Protocol Revision History including Summary of Changes 
Version 
Date 
Overall Rational for Changes 
Version 1.0 
03 APR 2018 
        N/A Original Protocol 
Version 2.0 
20 JUN 2018 
• 
Assessment of Quality of Life Questionnaires were changed, it was 
decided to use two instead of three questionnaires.  
• 
Kidney biopsy data will be recorded directly in CRF intsead of 
retrieved from the biopsy reports.  
• 
Any version of Banff classification can be used for classification of 
acute rejection episodes. 
• 
EudraCT number on first page is removed since the study was not 
submitted to any European regulatory authority. 
 
 
 
Version 3.0 
 
 
27 SEP 2020 
• 
The method of data collection will be changed from paper CRF 
to electronic CRF.  
• 
A study visit can be performed remotely if a subject is not able to 
visit the site.  
• 
Clarify the wordings “acute rejection episode” and “DSA 
rebound” by change wordings to “graft rejection episode”. 
• 
Clarify that creatinine and proteinuria results from graft 
rejection episodes will be collected as well as from the time for 
planned 1- and 2-Years visits if study start was after those visits 
should have taken place. 
Version 4.0 
22 NOV 2021 
• 
Updates due to change in CRO responsible for SAE and SUSAR 
handling. 
See Appendix 1 “Protocol Amendment History” for details of Amendment 03. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
3 (43) 
Synopsis 
Name of Sponsor/Company 
Hansa Biopharma AB (hereafter referred to as Hansa Biopharma) 
Title of the study 
A prospective observational, long term follow up study of patients treated with imlifidase prior to 
kidney transplantation 
Signatory Coordinating Investigator (s) 
Dr. Bengt von Zür-Muhlen  
Study Site(s) 
Six sites will be involved; 2 in Sweden, 1 in France and 3 in the US. 
Planned study period 
First subject first visit (FSFV) Q2 2018 
Last subject last visit (LSLV) Q3 2022 
Clinical Phase 
Observational study 
Background and Scientific Justification for Conducting the Study 
The rationale for the current protocol is to collect data from extended follow up in subjects that have 
received a kidney transplant following imlifidase dosing to provide a better understanding regarding 
the long-term outcome for these subjects. Data of parameters such as patient and graft survival, 
comorbidity, treatment of graft rejection episodes and quality of life as well as anti-drug antibody 
levels will be collected. 
This prospective, observational follow up study of subjects who have received imlifidase prior to 
kidney transplantation will provide important data to future prescribers and patients of the potential 
long-term benefits of imlifidase mediated transplantation. 
Primary objective:  
Evaluation of graft survival in subjects who have undergone kidney transplantation after imlifidase 
administration. 
Secondary Objectives: 
• 
Evaluation of long-term clinical outcomes of transplanted subjects treated with imlifidase in terms 
of patient survival, kidney function, comorbidity, treatments and quality of life. 
• 
Assessment of safety blood sampling in transplanted subjects treated with imlifidase 
• 
Assessment of donor specific antibodies (DSA) in transplanted subjects treated with imlifidase 
• 
Assessment of immunogenicity (anti-drug antibodies, ADA) in transplanted subjects treated with 
imlifidase 
Endpoints 
The primary endpoint of this study is to determine overall graft survival, defined as time from 
transplantation to graft loss at 1, 2, 3 and 5 years after first dose of imlifidase.  
Graft loss is defined as: Permanent return to dialysis for at least 6 weeks, re-transplantation, or 
nephrectomy. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
4 (43) 
Secondary Endpoints 
The following secondary endpoints will be evaluated at 1, 2, 3 and 5 years from the first dose of 
imlifidase: 
• 
Overall patient survival (time from transplantation to death for any cause)  
• 
Kidney function as evaluated by eGFR, P-creatinine, proteinuria  
• 
Number of graft rejection episodes (Banff classification) 
• 
Safety laboratory tests  
• 
Treatment of graft rejection episode 
• 
Comorbidity  
• 
DSA levels  
• 
Presence of BK virus  
• 
ADA as evaluated by anti-imlifidase IgG  
• 
Health related quality of life as evaluated by patient questionnaires  
Methodology 
This is a five year, long-term follow up, observational study. The study will primarily determine the 
time of graft survival in subjects who have received imlifidase prior to kidney transplantation. 
Subjects that have participated, or are currently participating, in the imlifidase kidney 
transplantation studies (called feeder studies) 13-HMedIdeS-02, 13-HMedIdeS-03, 14-HMedIdeS-
04 and 15-HMedIdeS-06 will be included. The subjects will attend 4 follow up visits, 1, 2, 3 and 5 
years after imlifidase administration.  
Study Procedures/Assessments 
At all visits, graft function (creatinine, eGFR, proteinuria) and time of graft survival will be 
assessed. Blood samples for analysis of DSAs, ADA and antibodies towards BK virus will be taken 
as well as total IgG and hematology samples. Information about patient survival, comorbidity 
(infections, malignancy, diabetes mellitus and cardiovascular events) and treatments of graft 
rejection episode (dialysis, plasmapheresis, medications) will be recorded. The subjects will be 
asked to complete QoL questionnaires.   
Number of subjects 
Up to 46 subjects will be included depending on subjects’ willingness to participate in the study.  
Diagnosis and main criteria for inclusion/exclusion  
Inclusion Criteria: 
1) Signed Informed Consent obtained before any study-related procedures 
2) Previous dosing with imlifidase followed by kidney transplantation and participation in one 
of the following clinical studies: 13-HMedIdeS-02, 13-HMedIdeS-03, 14-HMedIdeS-04 or  
15-HMedIdeS-06 
Exclusion Criteria: 
1) Individuals deemed unable to comply with the protocol 
2) Inability by the judgment of the investigator to participate in the study for other reasons 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
5 (43) 
Medicinal Product(S) 
Not applicable 
Statistical methods 
This is a long-term non-interventional study and for the evaluation and presentation of data 
descriptive techniques will be used. The data from the clinical assessments will be summarised by 
feeder study and time point. Summary statistics (n, arithmetic mean, standard deviation, median, 
minimum and maximum values) will be presented for continuous variables. Counts and, if relevant, 
percentages will be presented for categorical variables. The primary endpoint will be analysed by 
the Kaplan-Meier survival method. There will be no formal statistical hypothesis or testing because 
of the observational nature of the study. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
6 (43) 
 
Table of contents 
See Appendix 1 “Protocol Amendment History” for details of Amendment 03. ........... 2 
Synopsis ................................................................................................................................. 3 
List of Abbreviations .......................................................................................................... 10 
1. 
Introduction .......................................................................................................... 11 
1.1 
Background ............................................................................................................ 11 
1.2 
Rationale ................................................................................................................ 13 
1.3 
Benefit / Risk Aspects ............................................................................................ 14 
2. 
Study Objectives and Endpoints ......................................................................... 14 
2.1 
Objectives ............................................................................................................... 14 
2.2 
Endpoints ............................................................................................................... 14 
3. 
Investigational Plan .............................................................................................. 15 
3.1 
Overall Study Design ............................................................................................. 15 
3.1.1 
Overall Study Outline ............................................................................................ 16 
3.1.2 
Follow up Procedures ............................................................................................. 16 
3.2 
Study Schedule ....................................................................................................... 16 
3.3 
Planned number of study sites and subjects ........................................................... 16 
3.4 
Planned End of Study ............................................................................................. 16 
4. 
Study Population .................................................................................................. 16 
4.1 
General ................................................................................................................... 16 
4.2 
Selection Criteria .................................................................................................... 17 
4.2.1 
Inclusion Criteria .................................................................................................... 17 
4.2.2 
Exclusion Criteria .................................................................................................. 17 
4.3 
Discontinuation of Subjects ................................................................................... 17 
5. 
Study Procedures ................................................................................................. 17 
5.1 
Study Visits ............................................................................................................ 17 
5.2 
Flow Chart .............................................................................................................. 19 
6. 
Study assessments ................................................................................................ 20 
6.1 
Assessments related to Primary Endpoint .............................................................. 20 
6.1.1 
Graft Survival ......................................................................................................... 20 
6.2 
Assessments related to Secondary Endpoints ........................................................ 20 
6.2.1 
Patient survival ....................................................................................................... 20 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
7 (43) 
6.2.2 
Kidney function ...................................................................................................... 20 
6.2.3 
Kidney biopsy ........................................................................................................ 20 
6.2.4 
Graft rejection episodes ......................................................................................... 20 
6.2.5 
Treatment of graft rejection episodes ..................................................................... 20 
6.2.6 
Comorbidity ........................................................................................................... 21 
6.2.7 
Donor Specific Antibodies (DSA) ......................................................................... 21 
6.2.8 
Immunogenicity by Anti-Drug Antibodies (ADA) ................................................ 21 
6.2.9 
Health Related Quality of Life Questionnaire (HR-QoL) ..................................... 21 
6.3 
Safety and other Laboratory Samples .................................................................... 21 
7. 
Biological Sampling Procedures ......................................................................... 22 
7.1 
Handling, Storage and Destruction of Biological Samples .................................... 22 
7.2 
Chain of Custody of Biological Samples ............................................................... 22 
7.3 
Withdrawal of Informed Consent for Donated Biological Samples ...................... 22 
8. 
Adverse Events and Serious Adverse Events .................................................... 23 
8.1 
Definitions .............................................................................................................. 23 
8.1.1 
Adverse event ......................................................................................................... 23 
8.1.2 
Serious adverse event ............................................................................................. 23 
8.2 
Collection and Recording of Adverse Events ........................................................ 24 
8.2.1 
Variables ................................................................................................................ 24 
8.2.1.1 Causality assessment .............................................................................................. 24 
8.2.2 
Adverse Events Based on Signs and Symptoms .................................................... 25 
8.2.3 
Adverse Events Based on Examinations and Tests ............................................... 25 
8.2.4 
Follow up of Unresolved Adverse Events ............................................................. 25 
8.2.5 
Reporting of Serious Adverse Events .................................................................... 25 
8.2.6 
Reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) ........ 26 
8.3 
Adverse Events of Special Interest ........................................................................ 26 
8.4 
Pregnancy and Pregnancy Outcome ...................................................................... 26 
9. 
Study Management .............................................................................................. 27 
9.1 
Pre-study Activities ................................................................................................ 27 
9.2 
Monitoring of the Study ......................................................................................... 27 
9.3 
Source data verification ......................................................................................... 28 
9.4 
Audit and Inspection .............................................................................................. 28 
9.5 
Study Agreements .................................................................................................. 28 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
8 (43) 
10. 
Data Management ................................................................................................ 29 
10.1 
Case Report Form .................................................................................................. 29 
10.2 
Provider of Data Management ............................................................................... 29 
10.3 
Coding .................................................................................................................... 29 
10.4 
Handling of External Data ..................................................................................... 29 
11. 
Statistical Methods ............................................................................................... 29 
11.1.1 
Full Analysis Set (FAS) ......................................................................................... 30 
11.2 
Descriptive Statistics .............................................................................................. 30 
11.3 
Subject disposition ................................................................................................. 30 
11.3.1 
Demographics and Other Baseline Characteristics ................................................ 30 
11.3.2 
Concomitant Medication ........................................................................................ 30 
11.3.3 
Exposure and Compliance ..................................................................................... 30 
11.4 
Statistical analysis of Primary Endpoint ................................................................ 30 
11.5 
Primary endpoint – graft survival .......................................................................... 30 
11.6 
Statistical analysis of Secondary Endpoints ........................................................... 31 
11.6.1 
Graft loss not censored for death ........................................................................... 31 
11.6.2 
Patient survival ....................................................................................................... 31 
11.6.3 
Kidney function ...................................................................................................... 31 
11.6.4 
Kidney biopsy ........................................................................................................ 31 
11.6.5 
Number of graft rejection episodes ........................................................................ 31 
11.6.6 
Treatment of graft rejection episodes ..................................................................... 32 
11.6.7 
Comorbidity ........................................................................................................... 32 
11.6.8 
DSA levels ............................................................................................................. 32 
11.6.9 
BK virus ................................................................................................................. 32 
11.6.10 ADA ....................................................................................................................... 32 
11.6.11 Health related quality of life .................................................................................. 32 
11.7 
Safety Endpoints .................................................................................................... 32 
11.7.1 
Analysis of Adverse Events ................................................................................... 32 
11.7.2 
Analysis of Safety Variables .................................................................................. 32 
11.8 
Determination of Sample Size ............................................................................... 32 
12. 
Changes in Study Conduct or Planned Analyses .............................................. 33 
12.1 
Protocol Amendment(s) ......................................................................................... 33 
12.2 
Protocol Deviations ................................................................................................ 33 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
9 (43) 
12.3 
Changes to the Statistical Analysis Plan ................................................................ 33 
12.4 
Premature Termination or Suspension of the Study .............................................. 33 
13. 
Reporting and Publication .................................................................................. 34 
13.1 
Clinical Study Report ............................................................................................. 34 
13.2 
Confidentiality and Data Ownership ...................................................................... 34 
13.3 
Publications ............................................................................................................ 34 
13.4 
Publication Policy .................................................................................................. 34 
13.5 
Public disclosure .................................................................................................... 34 
14. 
Ethical and Regulatory Aspects .......................................................................... 34 
14.1 
Ethical Conduct of the Study ................................................................................. 34 
14.2 
Liabilities and Insurance ........................................................................................ 35 
14.3 
Independent Ethics Committee(s) and Institutional Review Boards (IRB) ........... 35 
14.4 
Regulatory Authority(ies) ...................................................................................... 35 
14.5 
Subject Information and Informed Consent ........................................................... 35 
14.6 
Subject Confidentiality .......................................................................................... 36 
15. 
Archiving ............................................................................................................... 36 
15.1 
Retention of Clinical Study Site Documentation ................................................... 36 
15.2 
Trial Master File ..................................................................................................... 37 
16. 
References ............................................................................................................. 38 
17. 
Appendix 1 ............................................................................................................ 39 
 
List of Tables 
Table 1. Summary table of clinical studies with imlifidase in the transplantation program.12 
Table 2. Study flow chart. .................................................................................................... 19 
Table 3. Safety hematology and clinical chemistry laboratory tests .................................... 22 
 
List of Figures  
Figure 1.Overall study outline .............................................................................................. 16 
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
10 (43) 
List of Abbreviations  
ADA 
Anti-Drug Antibody 
AE 
Adverse Event 
CKD 
Chronic Kidney Disease 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
DD 
Deceased Donor 
DSA 
Donor Specific Antibodies 
eGFR 
estimated Glomerular Filtration Rate 
EQ-5D-5L 
European Quality of Life -5 Levels 
FAS 
Full Analysis Set 
FDA 
US Food and Drug Administration  
GCP 
Good Clinical Practice 
HLA 
Human Leukocyte Antigen 
HR-QoL 
Health Related Quality of Life  
 
ICH 
International Conference on Harmonization 
IdeS 
Immunoglobulin G degrading enzyme of Streptococcus pyogenes 
IEC 
Independent Ethics Committee 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IVIg 
Intravenous Immunoglobulin 
KDQOL-SF 
Kidney Disease Quality of Life-Short Form 
KM 
Kaplan-Meier  
LD 
Living Donor 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFI 
Mean Florescence Intensity 
PE 
Plasma Exchange 
 
 
QA 
Quality Assurance 
RA 
Regulatory Authority 
SAB 
Single Antigen Bead  
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SDV 
Source Document Verification 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
11 (43) 
1. 
INTRODUCTION 
The company code initially used in this project was HMED-IdeS (sometimes abbreviated to 
IdeS) and thus many reports refer to this name. The International Nonproprietary Name (INN) 
imlifidase was recently assigned for the active substance and going forward this name will be 
used.  
1.1 
Background  
Renal transplantation is the preferred treatment choice for patients with end stage kidney 
disease since it increases survival and patient quality of life and results in substantial savings 
in health care costs compared to dialysis (Montgomery et al. 2005).  
Approximately one third of patients waiting for kidney transplantation are sensitized to 
human leukocyte antigen (HLA) and sensitization hampers the identification of a suitable 
donor (Iyer et al. 2014). The presence of strong HLA donor specific antibodies (DSAs) is a 
direct contraindication to transplantation because of the risk of hyper-acute antibody-mediated 
rejection with acute allograft loss. For transplant candidates who have antibodies, which react 
against a wide range of HLA, it can be difficult to find a donor against whom they have no 
antibodies. This is true both for patients waiting for a deceased donor kidney and for those 
within a paired donation program who have an available live donor against which they have 
DSAs. 
Data demonstrates that desensitization followed by transplantation of patients with DSAs is 
clearly associated with short- and long-term survival benefits compared to staying on dialysis 
(Montgomery et al. 2011; Vo et al. 2013; Orandi et al. 2014; Orandi et al. 2016). In addition, 
the patient’s quality of life is dramatically increased and there are substantial cost-savings 
associated with desensitization compared to dialysis (Vo et al. 2013). 
Imlifidase is an IgG-degrading enzyme of Streptococcus pyogenes that cleaves all four human 
subclasses of IgG with strict specificity. Cleavage of IgG generates one F(ab’)2- and one 
homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG (HMed 
doc. No. 2012-003) (Wenig et al. 2004; Vincents et al. 2004; von Pawel-Rammingen et al. 
2002). Imlifidase-mediated IgG degradation constitutes a novel therapeutic principle for the 
treatment of IgG-driven human diseases. 
Hansa Biopharma AB has performed in vitro studies and clearly demonstrated that imlifidase 
effectively cleaves purified IgG as well as IgG in serum from human and rabbit. Imlifidase is 
very specific in that no other substrate has been found (HMed Doc. No. 2012-003). In 
addition, imlifidase treatment rapidly and substantially cleaved anti-HLA IgG in serum from 
sensitized chronic kidney disease (CKD) grade 5 patients in vitro (HMed Doc. No. 2012-005). 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
12 (43) 
The reactivity to individual HLA-antigens was reduced below the critical Mean Florescence 
Intensity (MFI) acceptable for transplantation and a positive crossmatch test was turned into 
negative. Imlifidase offers a unique and powerful approach for removing the impenetrable 
immunology barrier HLA antibodies present and would allow potentially life-saving 
transplants to highly sensitized patients who are currently not eligible for kidney 
transplantation. 
The clinical studies performed or ongoing with imlifidase within the transplantation program 
are summarised in Table 1. 
 
Table 1. Summary table of clinical studies with imlifidase in the transplantation program. 
Study No / 
EudraCT No 
Phase / 
Subjects 
Doses / 
Follow up 
time 
Main objectives 
Comments 
Status / 
Country /  
Subject 
Numbers 
11-HMedIdeS-01 / 
2012-000 969-21 
I / 
Healthy 
subjects  
0.010, 0.040, 
0.12 and 
0.24 mg/kg 
BW 
 
64 d 
Safety 
First-in-man, double 
blind, randomized, 
single ascending 
dose, 20 active,  
9 placebo. 
IgG completely 
cleaved within 1-2 h. 
Safe and well 
tolerated. 
 
Completed / 
SE / 
 
N=29 
13-HMedIdeS-02 / 
2013-005417-13  
II / 
CKD 
Patients  
0.12 and 
0.25 mg/kg 
BW given 
once or 
twice within 
48 h / 
 
64 d 
Efficacy in CKD 
patients defined as 
imlifidase dosing 
scheme resulting in 
HLA antibody 
levels acceptable 
for transplantation, 
within 24 h from 
dosing. 
Safety in the 
transplantation 
setting. 
 
Single arm with 
ascending doses. 
Primary efficacy 
endpoint reached. 
Safe and well 
tolerated. 
One patient was 
transplanted (not part 
of protocol). 
Deceased donor. 
Completed / 
SE / 
 
N= 8 
13-HMedIdeS-03 / 
2014-000712-34  
II / 
Patients  
0.25 and 0.5 
mg/kg / 
 
180 d 
Safety in the 
transplantation 
setting.  
Efficacy defined as 
HLA antibody 
levels acceptable 
for transplantation. 
Similar design as 13-
HMedIdeS-02 but 
transplantation part of 
protocol. 
Deceased and living 
donors. Safe and well 
tolerated.  All 
patients desensitized 
and transplanted 
 
Completed / 
SE / 
 
N=10 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
13 (43) 
Study No / 
EudraCT No 
Phase / 
Subjects 
Doses / 
Follow up 
time 
Main objectives 
Comments 
Status / 
Country /  
Subject 
Numbers 
14-HMedIdeS-04 / 
EudraCT: NA 
IND 124301  
II / 
Patients  
0.24 and 0.5 
mg/kg /        
 
180 d 
Safety in 
combination with 
Cedars Sinai’s 
“standard protocol” 
for desensitization 
of highly sensitized 
patients. Efficacy in 
prevention of 
ABMR. 
Investigator 
sponsored IND. 
Imlifidase combined 
with rituximab and 
IVIg. 
All transplantations 
successful except one 
graft loss which 
occurred due to non-
HLA and non-IgG 
ABMR.  Biopsy 
suggested rejection 
due to IgM and IgA. 
 
Completed / 
US / 
 
Total N=17 
Analysis and 
reporting 
ongoing. 
 
 
15-HMedIdeS-06 / 
2016-002064-13 
IND: 128074 
II / 
Patients  
0.25 and 0.5 
mg/kg /  
 
Primary 
endpoint:   
24 h  
Safety: 
180 d 
Efficacy in creating 
a negative 
crossmatch test.  
Safety in the 
transplantation 
setting. 
Deceased and living 
donors. 
Target population 
cannot be 
transplanted with 
current available 
methods for 
desensitization.  
All transplantations 
(18) were successful 
except one graft loss. 
For one patient, 
imlifidase dosing was 
interrupted due to 
allergic reaction and 
the patient was not 
transplanted. 
 
Ongoing /   
US, FR & 
SE / 
 
Total N=19 
Recruitment 
ended 15 
Dec 2017. 
 
BW=body weight, h=hours, d=days  
 
In completed (13-HMedIdeS-02, 13-HMedIdeS-03 and 14-HMedIdeS-04) and ongoing studies 
(15-HMedIdeS-06), subjects have been treated with imlifidase and transplanted with kidneys 
from deceased or living donors. The follow up periods were 6 months post transplantation 
except for 13-HMedIdeS-02 with 2 months follow up. The current protocol aims at collecting 
key information regarding overall graft function and safety from all subjects that have been 
treated with imlifidase prior to kidney transplantation. 
1.2 
Rationale 
The rationale for the current protocol is to collect data from extended follow up in subjects that 
have received a kidney transplant following imlifidase dosing to provide a better understanding 
regarding the long-term outcome for these subjects. Data of parameters such as patient and graft 
survival, kidney function, comorbidity, treatment of graft rejection episodes and quality of life 
as well as anti-drug antibody levels will be collected. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
14 (43) 
1.3 
Benefit / Risk Aspects 
The subjects included in this study have received imlifidase prior to kidney transplantation in 
previous clinical studies. The current study is performed to collect long-term follow up data 
on graft function and safety. Most of the assessments performed under the current protocol 
are already part of the follow up within standard of care for these subjects and consequently 
they will not impose any additional risk.  
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Objectives 
Primary Objective 
The primary objective of this study is to evaluate graft survival in subjects who have 
undergone kidney transplantation after imlifidase administration. 
Secondary Objectives 
The secondary objectives include: 
• Evaluation of long-term clinical outcomes of transplanted subjects treated with imlifidase 
in terms of patient survival, kidney function, comorbidity, treatments and quality of life. 
• Assessment of safety blood sampling in transplanted subjects treated with imlifidase 
• Assessment of donor specific antibodies (DSA) in transplanted subjects treated with 
imlifidase 
• Assessment of immunogenicity (anti-drug antibodies, ADA) in transplanted subjects treated 
with imlifidase 
2.2 
Endpoints 
Primary Endpoint 
The primary endpoint of this study is to determine overall graft survival, defined as time from 
transplantation to graft loss at 1, 2, 3 and 5 years after first dose of imlifidase.  
Graft loss is defined as: Permanent return to dialysis for at least 6 weeks, re-transplantation, 
or nephrectomy. If dialysis is used to define graft loss, the date of graft loss will be the first 
day of the last ongoing dialysis period reported (EMA Guideline on clinical investigation of 
immunosuppressants for solid organ transplantation 2008) . 
Secondary Endpoints 
The following secondary endpoints will be evaluated after the first dose of imlifidase at the 
time points 1, 2, 3 and 5 years: 
• Overall patient survival defined as time from transplantation to death for any cause  

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
15 (43) 
• Kidney function as evaluated by eGFR, P-creatinine, proteinuria   
• Number of graft rejection episodes (classified by Banff , (Haas et al. 2018)) 
• Safety laboratory tests (hematology, total IgG)   
• Treatment of graft rejection episodes  
• Comorbidity  
• DSA levels as evaluated by SAB-HLA analysis  
• Presence of BK virus   
• ADA as evaluated by anti-imlifidase IgG   
• Health related quality of life (HR-QoL) as evaluated by patient questionnaires EQ-5D-
5L and KDQOL-SF. 
 
3. 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design  
This is a five year, long-term follow up, observational study. Centers that have participated, or 
are currently participating, in selected imlifidase kidney transplantation studies (referred to as 
“feeder studies”) will be contacted and requested to approach subjects for enrolment in the 
study. The following studies will be considered feeder studies: 13-HMedIdeS-02, 13-
HMedIdeS-03, 14-HMedIdeS-04 and 15-HMedIdeS-06. Up to 46 subjects will be included 
depending on subjects’ willingness to participate in the study.  
The study will primarily determine the time of graft survival in subjects who have received 
imlifidase prior to kidney transplantation. The subjects will attend 4 follow up visits, 1, 2, 3 and 
5 years after imlifidase administration. Some subjects will not perform all 4 visits because the 
study start will be after the subjects’ first visit should have taken place.  
Kidney function (creatinine, eGFR, proteinuria) and graft survival will be assessed. Graft 
rejection episodes will be determined by Banff classification. Information from kidney biopsies 
performed within standard of care will be collected.  Blood samples for analysis of DSAs, ADA 
and antibodies towards BK virus will be taken as well as total IgG and safety hematology 
samples. Medically relevant comorbidity (infections, malignancy, diabetes mellitus and 
cardiovascular events) will be recorded. Information about treatments of graft rejection 
episodes will be recorded (dialysis, plasmapheresis, medications). At all visits, the subjects will 
be asked to complete QoL questionnaires.  The overall study outline is summarized in Figure 
1. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
17 (43) 
4.2 
Selection Criteria 
Subjects must meet all inclusion criteria and no exclusion criteria to be eligible for the study.  
4.2.1 
Inclusion Criteria 
• 
Signed Informed Consent obtained before any study-related procedures 
• 
Previous dosing with imlifidase followed by kidney transplantation and participation in 
one of the following clinical studies: 13-HMedIdeS-02, 13-HMedIdeS-03, 14-
HMedIdeS-04 or 15-HMedIdeS-06  
Note: The primary objective in this study is overall graft survival after imlifidase 
treatment therefore the subjects can also be included in the event that the subject did not 
fully complete the feeder study.  
4.2.2 
Exclusion Criteria 
• 
Individuals deemed unable to comply with the protocol 
• 
Inability by the judgement of the investigator to participate in the study for other reasons 
4.3 
Discontinuation of Subjects  
The subjects have the right to withdraw from the study at any time for any reason, without the 
need to justify their decision. However, the investigator should record the reason for the 
subject’s withdrawal, if possible. The investigator also has the right to withdraw subjects. In 
either event, the investigator must notify monitor. 
If a subject prematurely discontinues participation, the End of Study Form (with date and reason 
for discontinuation) in the CRF must be completed. 
 
5. 
STUDY PROCEDURES 
5.1 
Study Visits  
For each subject the duration of the study will not exceed 5 years and 6 months post imlifidase 
dosing. 
All subjects considered for the study must be informed about the study, verbally and in writing, 
and give their written consent before any study procedure is performed. After informed consent 
is obtained, pre-study visit data such as information on graft survival and patient survival can 
be collected and entered in the CRF.   
Some subjects will not perform all 4 visits because the study start will be after the subjects’ first 
visit should have taken place.  
If a subject is not able to attend a planned visit at the site, the visit can be performed remotely. 
The blood sampling should be performed at the local laboratory (if possible) and QOL forms 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
18 (43) 
sent to the subject. The following activities and assessments will be performed at 1 year (+/- 2 
months), 2 years (+/- 4 months), 3 years (+/- 4 months) and 5 years (+/- 6 months) post 
imlifidase dosing: 
• Check of inclusion and exclusion criteria will be performed at the first visit for each 
subject after 1, 2 or 3 years post imlifidase dosing. 
• Subjects shall complete QoL questionnaires (EQ-5D-5Land KDQOL-SF) 
• Evaluation of graft survival 
• Record patient survival (if applicable, date and cause of death)  
• Safety laboratory tests (see Table 3) 
• P-creatinine, eGFR and U-proteinuria tests 
• DSA samples 
• ADA sample 
• BK virus sample 
• Record comorbidity such as infections, malignancy, diabetes mellitus and 
cardiovascular events 
• Record graft rejection episodes (classified by Banff ) 
• If applicable, record information from standard of care kidney biopsy reports   
• Record treatments of graft rejection episodes (PE, IVIg, dialysis, other) 
• Record current immunosuppressive medication 
• Record and report AEs caused by study procedure or a clinically significant safety 
lab value  
 
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
20 (43) 
6. 
STUDY ASSESSMENTS 
6.1 
Assessments related to Primary Endpoint 
The time points for all study assessments are shown in the study flow chart (Table 2). 
Laboratory sampling, shipment, and analysis will be described in detail in the laboratory 
manual. 
6.1.1 
Graft Survival  
The primary endpoint of this study is to determine overall graft survival, defined as time from 
transplantation to graft loss. Graft loss is defined as permanent return to dialysis for at least 6 
weeks, re-transplantation, or nephrectomy. If dialysis is used to define graft loss, the date of 
graft loss will be the first day of the last ongoing dialysis period reported.  
6.2 
Assessments related to Secondary Endpoints 
6.2.1 
Patient survival 
Overall patient survival is defined as time from transplantation to death for any cause. If 
applicable, information on time and cause of death will be recorded. 
6.2.2 
Kidney function  
Kidney function will be evaluated by P-creatinine and calculation of estimated filtration rate 
(eGFR) by MDRD/CKD-EPI formula (performed by Sponsor). Proteinuria will be measured 
by dipstick. The samples will be taken at the time points presented in the study flow chart. 
Creatinine and proteinuria results from graft rejection episodes will be collected as well as from 
the time for planned 1- and 2-years visit if study start was after those visits should have taken 
place.  
6.2.3 
Kidney biopsy 
If standard of care kidney biopsies are performed for any reason, at any time-point, e.g. 
suspected rejections, information will be collected and recorded in the CRF. 
6.2.4 
Graft rejection episodes 
Information about the occurrence of graft rejection episodes will be collected, following Banff 
classification. 
6.2.5 
Treatment of graft rejection episodes 
Information about treatments of graft rejection episodes will be recorded (e.g dialysis, 
plasmapheresis and medications). 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
21 (43) 
6.2.6 
Comorbidity 
Information about comorbidities that are medically relevant and registered in the subjects’ 
medical record will be collected. Medically relevant comorbidity are e.g. infections, 
malignancy, diabetes mellitus and cardiovascular events. 
6.2.7 
Donor Specific Antibodies (DSA) 
Samples for determination of DSAs will be analysed in LABScreen single antigen HLA class 
I and class II assays. The assays allow determination of the mean fluorescence intensity (MFI) 
of antibodies in patient serum reacting to an array of individual HLA immobilized to beads. 
Analyses of DSAs will be performed centrally, at Hansa Biopharma , Lund. The date and time 
of collection of each sample will be recorded on the sample log and in the CRF.  
Samples for DSA will also be analysed by the hospital laboratory and the results will be 
evaluated by the Investigator and recorded in the CRF. 
6.2.8 
Immunogenicity by Anti-Drug Antibodies (ADA) 
Samples for the determination of anti-drug antibody (ADA) levels in serum will be analysed 
for anti-imlifidase IgG using a customized imlifidase ImmunoCAP test. The analysis will be 
performed at the central laboratory, Thermofisher Scientific, Immuno Diagnostics, Service 
Laboratory, Alleröd, Denmark. Full details of the analytical method used, and the analysis 
results will be detailed in a separate bioanalytical report. The ADA samples will be taken at the 
times presented in the study flow chart. The date and time of collection of each sample will be 
recorded on the laboratory requisition form and in the CRF.  
6.2.9 
Health Related Quality of Life Questionnaire (HR-QoL)  
At all visits, two patient questionnaires will be used to assess health related quality of life. 
European Quality of Life-5 levels (EQ-5D-5L) and Kidney Disease Quality of Life 
Questionnaire-short form (KDQOL-SF). The individual guidelines for the questionnaires will 
be followed when administering the forms. 
6.3 
Safety and other Laboratory Samples 
The investigator will review the laboratory results and evaluate and document whether the 
results are normal or abnormal and whether abnormal results are clinically or non-clinically 
significant. The local hospital laboratory will be used for the analyses and updated laboratory 
certificate and reference ranges will be collected. The samples will be taken at the times 
presented in the study flow chart (Table 2). The safety hematology and clinical chemistry tests 
will be the following: 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
22 (43) 
 
Table 3. Safety hematology and clinical chemistry laboratory tests 
Hematology1) 
B-Hemoglobin 
B-Differential analysis of leucocytes 
B-Thrombocytes 
Clinical Chemistry 
P-IgG 
1) May be taken as serum samples if that is standard procedure at local lab  
Virology test for BK will also be taken at the local hospital laboratory. 
 
7. 
BIOLOGICAL SAMPLING PROCEDURES 
7.1 
Handling, Storage and Destruction of Biological Samples 
Details on handling of biological samples will be described in the laboratory manual that will 
be provided to the center prior to inclusion of the first patient. 
ADA and DSA samples may be stored for maximum 2 years after completion of the study 
report according to local regulations. 
Analyses cannot be used or re-used for purposes different from the ones stated in the protocol. 
Analyses not described in this protocol can only be performed after obtaining the required 
approvals and new written informed consent. 
7.2 
Chain of Custody of Biological Samples 
A full chain of custody is maintained for all samples throughout their life cycle. 
The principal investigator keeps full traceability of collected biological samples from the 
patients while in storage at the centre until shipment and keeps documentation of receipt of 
arrival. 
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed. 
Hansa Biopharma keeps oversight of the entire life cycle through internal procedures, 
monitoring of study sites and auditing of external laboratory providers. 
7.3 
Withdrawal of Informed Consent for Donated Biological Samples 
If a subject withdraws consent to the use of biological samples donated the samples will be 
disposed/destroyed, if not already analysed and documented. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
23 (43) 
The principal investigator: 
• 
will ensure that subject withdrawal of informed consent is notified immediately to Hansa 
Medical 
• 
will ensure that biological samples from that subject, if stored at the study site, are 
immediately identified, disposed/destructed and the action documented.  
• 
will ensure the laboratory(ies) holding the samples is/are informed about the withdrawn 
consent immediately and that samples are disposed/destructed, and the action 
documented returned to the study site. 
Hansa Biopharma ensures the laboratory(ies) holding the samples is/are informed about the 
withdrawn consent immediately and that samples are disposed/destructed, and the action 
documented returned to the study site. 
In the event that analysis/research has already been performed, Hansa Biopharma will retain 
the results and associated data for regulatory reasons, but these will not be used in any 
subsequent analyses. 
8. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.1 
Definitions 
8.1.1 
Adverse event 
An adverse event (AE) is the development of an undesirable medical condition or the 
deterioration of a pre-existing medical condition following or during exposure to a 
pharmaceutical product, whether or not considered causally related to the product. Relationship 
to the study drug will be deemed as not related, unlikely, possible or probable. An undesirable 
medical condition can be symptoms (e.g., nausea and chest pain), signs (e.g., tachycardia and 
enlarged liver) or the abnormal results of an investigation (e.g., laboratory findings and 
electrocardiograms).  
In cases of surgical or diagnostic procedures, the condition/illness leading to such a procedure 
is considered as the AE rather than the procedure itself.  
In case of a fatality, the cause of death is considered as the AE, and the death is considered as 
its outcome. 
8.1.2 
Serious adverse event 
A serious adverse event (SAE) is an AE or suspected adverse reaction (SAR) that is considered 
"serious" if, in the view of either the investigator or Hansa Biopharma, it results in any of the 
following outcomes: 
• 
Results in death 
• 
Is immediately life-threatening 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
24 (43) 
• 
Requires in-patient hospitalisation or prolongation of existing hospitalisation.  
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital abnormality or birth defect 
• 
Is an important medical event that may jeopardise the subject or may require medical 
intervention to prevent one of the outcomes listed above.  
Life-threatening event: An adverse event or suspected adverse reaction is considered "life-
threatening" if, in the view of either the investigator or Hansa Biopharma, its occurrence places 
the patient or subject at immediate risk of death. It does not include an adverse event or 
suspected adverse reaction that, had it occurred in a more severe form, might have caused death.   
Disability is defined as a substantial disruption in a person’s ability to conduct normal life 
functions. 
Hospitalisation: Admittance to an emergency room for observation without being admitted 
to the hospital may be considered to be an AE but is not considered as an SAE. However, 
complications that occur during hospitalization are AEs, and if a complication prolongs 
hospitalization, the event is considered serious. 
8.2 
Collection and Recording of Adverse Events 
In clinical studies, an AE/SAE can occur at any time after signing of the informed consent until 
the end of the study, including run-in or washout periods, even if no study treatment has been 
administered, e.g., an AE can be related to a procedure in the protocol.  
AEs will therefore be collected on the AE CRF according to the information in section 8.3. 
8.2.1 
Variables 
The following variables will be recorded in the CRF for each AE; description of the AE, the 
date and time (if applicable) when the AE started and stopped, severity based on Common 
Terminology Criteria for Adverse Events grading (CTCAE v.4.03) whether the AE is serious 
or not, causality rating, action taken, and outcome. 
8.2.1.1 Causality assessment   
For each reported AE the investigator will assess the relationship of the event to study 
procedures using the following criteria: 
• Unrelated: applicable to an AE that occurs when the subject was not exposed to study 
treatment or another cause is obvious (e.g. if a lab abnormality is unrelated to the study 
procedure the investigator would tick the 'unrelated' box, and then specify as to what 
they consider the lab abnormality was related to). 
• Related: applicable to AEs where there is a connection with study procedures.  
For SAEs, causal relationship will also be assessed for any study procedure.  

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
25 (43) 
8.2.2 
Adverse Events Based on Signs and Symptoms 
When collecting AEs, the recording of diagnoses is preferred (when possible) rather than 
recording a list of signs and symptoms, for example: congestive heart failure rather than low 
ejection fraction, rales and dyspnea. However, if a diagnosis is known and there are other signs 
or symptoms that are not generally part of the diagnosis, the diagnosis and each sign or 
symptom not part of the diagnosis will be recorded separately, for example: congestive heart 
failure and conjunctivitis. 
8.2.3 
Adverse Events Based on Examinations and Tests 
If safety lab values are judged as clinically significant, they will be captured as AEs and if SAE 
criteria is fulfilled they will also be SAEs. 
Wherever possible the reporting investigator uses the clinical, rather than the laboratory term 
(e.g., anaemia versus low haemoglobin value). 
8.2.4 
Follow up of Unresolved Adverse Events 
Any AEs that are unresolved at the subject’s last AE assessment in the study are followed up 
by the investigator until stabilization, for as long as medically indicated or the overall clinical 
outcome of the subject is known, unless the subject is documented as “lost to follow up”. All 
SAEs and AEs leading to discontinuation should be followed until the event resolves, stabilizes, 
or returns to baseline.  
Reasonable attempts to obtain this information must be made and documented. Hansa 
Biopharma retains the right to request additional information for any subject with ongoing 
AE(s)/SAE(s) at the end of the study, if judged necessary. 
8.2.5 
Reporting of Serious Adverse Events 
All SAEs have to be reported, whether or not considered related to the investigational product, 
or to the study procedure(s), on a separate SAE form. In the Adverse Event form, it will be 
added that the AE is considered serious. SAEs will be recorded from the time of informed 
consent.  
An assigned contract research organisation (Primevigilance) will be responsible for reporting 
all SAEs to Regulatory Authorities (RA) in accordance with International Conference on 
Harmonisation ), Good Clinical Practice (GCP) ) and local regulations.  
As soon as the Investigator is aware of a potential SAE he/she should contact Primevigilance 
by e-mail no later than 24 hours after the knowledge of such a case. At the time of initial 
reporting the investigator must provide as a minimum requirement, subject number, birth date, 
description of the SAE and a preliminary assessment of causality.  
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
26 (43) 
Contact Information: 
CRO: 
Primevigilance 
e-mail: 
  
 
For fatal or life-threatening adverse events where important or relevant information is missing, 
active follow up is undertaken immediately. Investigators or other site personnel inform Hansa 
Biopharma and monitor of any follow up information on a previously reported SAE 
immediately but no later than within 24 hours of when he or she becomes aware of it. The 
monitor or Hansa Biopharma will advise the investigator/study site personnel how to proceed. 
The SAE reporting procedures are detailed in the study specific Safety Management Plan. This 
plan is an agreement between the Hansa Biopharma, and Primevigilance. 
8.2.6 
Reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs)  
Suspected Unexpected Serious Adverse Reactions (SUSARs) must be reported to RAs. A 
suspected serious adverse reaction is any SAE for which there is a reasonable possibility that 
the investigational product caused the adverse event. A serious adverse reaction is considered 
"unexpected" if it is not listed in the reference safety information section of the investigator 
brochure or is not listed at the specificity or severity that has been observed. 
SUSARs with an outcome of death or which are life threatening must be reported to the 
relevant RAs within 7 calendar days, all other SUSARs must be submitted within 15 calendar 
days. The SUSAR reporting procedures are detailed in the study Safety Management Plan. 
This plan is an agreement between the Hansa Biopharma, and Primevigilance. Hansa 
Biopharma will notify the appropriate RA(s) and all participating study investigators of any 
SUSARs on an expedited basis and in accordance with applicable regulations. In addition, 
Hansa Biopharma is responsible for informing all investigators in all other ongoing studies 
involving imlifidase about all SUSARs.  
It is the responsibility of the site investigator to promptly notify the Independent Ethics 
Committee (IEC) and other appropriate institutional regulatory bodies of all SUSARs 
received involving risk to human subjects as per their applicable requirements 
8.3 
Adverse Events of Special Interest 
Adverse events caused by a procedure in the protocol (such as blood sampling) or a clinically 
significant safety lab value are the only AEs that will be captured and reported in the study. If 
the lab value is attributable to worsening renal function, rejection, or natural progression of 
disease, it will not be reported as AE. 
8.4 
Pregnancy and Pregnancy Outcome 
Pregnancy was an exclusion criterion in the feeder studies and a pregnancy test was performed 
at the screening visit in each study. No pregnancies were reported during the clinical studies.  

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
27 (43) 
If a subject becomes pregnant during the current study, the subject will continue in the study 
according to study protocol, if possible. A Pregnancy Report Form must be sent by the 
investigator to Primevigilance at the latest within two weeks of learning of the pregnancy. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth 
or congenital abnormality) will be followed up on the Pregnancy Report Form even after the 
subject has completed or discontinued the study. Primevigilance will follow up on pregnancy 
outcome 4 weeks after the projected due date.  
Pregnancy itself is not considered an AE or SAE, but any event occurring during pregnancy 
that meets serious criteria must be reported to Hansa Biopharma and will be handled as a 
SAE. Spontaneous abortions, congenital abnormalities/birth defects are always considered to 
be SAEs and will be reported and followed up in accordance with other SAEs. Any SAE 
occurring as a result of a post-study pregnancy and considered reasonably related to the study 
drug by the investigator will be reported to HansaBiopharma (or designee). 
9. 
STUDY MANAGEMENT 
9.1 
Pre-study Activities 
Before the first subject is entered into the study, it may be necessary for a representative of 
Hansa Biopharma to visit the investigational study site for a pre-study visit to: 
Discuss with the investigator(s) (and other personnel involved with the study) their 
responsibilities with regard to protocol adherence and the responsibilities of Hansa Biopharma 
or its representatives.  
Before the first subject is entered into the study, a Hansa Biopharma representative will review 
and discuss the requirements of the clinical study protocol and related documents with the 
investigational staff and also train them in any study specific procedures and system(s) utilized 
at a site initiation visit. 
The principal investigator will ensure that appropriate training relevant to the study is given to 
all staff, and that any new information relevant to the performance of this study is forwarded to 
the staff involved. 
The principal investigator will maintain a record of all individuals involved in the study 
(medical, nursing and other staff). 
9.2 
Monitoring of the Study 
During the study, a Hansa Biopharma representative will have regular contacts with the study 
site, including visits to: 
• 
Provide information and support to the investigator(s). 
• 
Confirm that facilities remain acceptable. 
• 
Confirm that the investigational team is adhering to the protocol, ICH-GCP, data are 
being accurately and timely recorded in the CRFs. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
28 (43) 
• 
Perform Source Data Verification (SDV) (a comparison of the data in the CRFs with the 
subject’s medical records at the hospital or practice, and other records relevant to the 
study) including verification of informed consent of participating patients.  
• 
If a subject withdraws informed consent to the use of their biological samples; ensure this 
is 
reported 
to 
Hansa 
Biopharma 
and 
biological 
samples 
are 
identified, 
disposed/destructed accordingly, and the action is documented, and reported to the 
subject. 
Hansa Biopharma and the CRO will be available between visits if the investigator(s) or other 
staff at the center needs information and advice about the study conduct. 
9.3 
Source data verification 
Source data is defined in ICH-GCP. Except for SAEs, which must always be source data 
verified the extent to which SDV will be carried out must be decided, specified and detailed in 
the Monitoring Plan. For all data recorded, the source document must be defined in a source 
document agreement at each trial site. There must only be one source defined at any time for 
any data elements.  
9.4 
Audit and Inspection 
The investigator will make all the study-related source data and records available at any time 
to Quality Assurance (QA) auditor(s) mandated by Hansa Biopharma, or to domestic/foreign 
regulatory inspectors or representatives from IECs/IRBs who may audit/inspect the study. 
The main purposes of an audit or inspection are to assess compliance with the study protocol 
and the principles of ICH-GCP including the Declaration of Helsinki and all other relevant 
regulations. 
The subjects must be informed by the investigator and in the Informed Consent Documents that 
authorised Hansa Biopharma representatives and representatives from Regulatory Authorities 
and IECs/IRBs may wish to inspect their medical records. During audits/inspections the 
auditors/inspectors may copy relevant parts of the medical records. No personal identification 
apart from the screening number will appear on these copies. 
The investigator should notify without any delay of any inspection by a RA or IEC/IRB. 
9.5 
Study Agreements 
The principal investigator must comply with all the terms, conditions, and obligations of the 
clinical study agreement for this study. In the event of any inconsistency between this clinical 
study protocol and the clinical study agreement, the clinical study protocol will prevail. 
Agreements between Hansa Biopharma and the principal investigator must be in place before 
any study-related procedures can take place, or subjects be enrolled. 
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
29 (43) 
10. 
DATA MANAGEMENT 
10.1 
Case Report Form 
 An electronic case report form (eCRF) system provided by a CRO will be used for data 
capture. The system is validated and access at all levels to the system is granted/revoked 
following Hansa Biopharma and vendor procedures, in accordance with regulatory and 
system requirements. 
After the study database is declared clean and released to the statistician, a final copy of the 
database will be stored at HansaBiopharma. The investigator will also receive a copy of the trial 
site’s final and locked data (including audit trail, electronic signature, meta data and queries) as 
write-protected PDF-files produced by the CRO. The PDF-files will be stored on a CD/DVD 
and will be provided to the investigator before access to the eCRF is revoked.   
10.2 
Provider of Data Management 
All data management procedures will be outsourced to a CRO. Activities will be specified in a 
Data Management Plan prepared by the CRO and reviewed and approved by Hansa Biopharma. 
The plan will be issued before data collection begins and will describe all functions, processes 
and specifications for data collection, cleaning and validation. 
10.3 
Coding 
For medical coding, e.g. AEs, medical history and concomitant medication, the most recent 
versions of the Medical Dictionary for Regulatory Activities (MedDRA) and WHO Drug will 
be used at study closure (unless decided otherwise by Hansa Biopharma).  
The coding will be outsourced to a CRO. All coding performed will be approved by Hansa 
Biopharma prior to study closure/database lock. 
10.4 
Handling of External Data 
If central laboratories or other external data transfers from vendors to Hansa Biopharma will be 
transmitted, it will be performed in a secure environment according to a Data Transfer 
Specification. 
 
11. 
STATISTICAL METHODS 
All analyses will be detailed in a separate Statistical Analysis Plan (SAP). As this is a long-
term non-interventional study, it is anticipated that the first analysis of the data will occur six 
months after the first patient first visit. Thereafter, yearly summary analysis of the data will be 
performed. Summary analysis can also be done ad hoc during the study. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
30 (43) 
11.1.1 Full Analysis Set (FAS) 
The Full Analysis Set will be defined as all patients enrolled. Because of the non-interventional 
nature of this study no other analysis set will be defined and all data presentations and analyses 
will be based on the FAS. 
11.2 
Descriptive Statistics 
The data from the clinical assessments, including demographics and other baseline 
characteristics, will be summarised by feeder study and time point using descriptive 
techniques. Summary statistics (n, arithmetic mean, standard deviation, median, minimum 
and maximum values) will be presented for continuous variables (absolute values at each time 
point and, if relevant, changes from baseline) and counts and, if relevant, percentages will be 
presented for categorical variables. Where appropriate, the presentation of results will include 
confidence intervals of estimated treatment differences and plots.  
11.3 
Subject disposition 
The number of subjects in FAS will be summarized by feeder study. Furthermore, the number 
of subjects who withdraw from the study will be summarised overall, by withdrawal time, by 
reason for withdrawal and by feeder study.  
11.3.1 Demographics and Other Baseline Characteristics 
The subject’s demographics and other baseline characteristics will be summarised by feeder 
study. 
11.3.2 Concomitant Medication 
Current immunosuppressive medication will be summarised by anatomical therapeutic 
chemical (ATC) code and generic drug name for each feeder study. 
11.3.3 Exposure and Compliance 
Since this is a non-interventional follow-up study exposure and compliance will not be 
calculated. 
11.4 
Statistical analysis of Primary Endpoint 
11.5 
Primary endpoint – graft survival 
The primary endpoint, overall graft survival, is defined as time from transplantation to graft 
loss evaluated at 1, 2, 3 and 5 years after first dose of imlifidase. Graft loss is defined as: 
Permanent return to dialysis for at least 6 weeks, re-transplantation or nephrectomy. If 
dialysis is used to define graft loss, the date of graft loss will be the first day of the last 
ongoing dialysis period reported.  
The primary endpoint will be analysed by the Kaplan-Meier survival method. The overall graft 
survival will be tabulated and presented graphically with 95% confidence limits. The primary 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
31 (43) 
analysis will be based on intervals of 1 year, but the first annual summary analyses may be 
based on shorter intervals which will be defined in the SAP. The following events will be 
censored at the time of occurrence: withdrawal from the study without graft loss, death not 
caused by graft loss, evaluation time point (the yearly evaluations) and end of study without 
graft loss. The KM analysis is in this study not comparative because of the non-interventional 
nature of the study. Hence, there will be no formal statistical hypothesis or testing. 
The reason for graft loss will be tabulated by time. 
Explorative analyses assessing the influence of age and other baseline characteristics may be 
defined in the SAP. 
11.6 
Statistical analysis of Secondary Endpoints 
11.6.1 Graft loss not censored for death 
This endpoint is defined as the primary endpoint except that death for any cause also counts as 
a graft loss and therefore this event will not be censored. The endpoint will be analysed and 
presented as the primary endpoint. 
11.6.2 Patient survival 
Overall patient survival is defined as time from transplantation to death for any cause evaluated 
at 1, 2, 3 and 5 years. The analysis will be as for the primary endpoint. The following events 
will be censored: withdrawal from the study, evaluation time point (the yearly evaluations) and 
end of study. 
11.6.3 Kidney function 
The kidney function will be evaluated by eGFR, P-creatinine and proteinuria at 1, 2, 3 and 5 
years. The calculation of eGFR will be described in the SAP. The three parameters will be 
summary tabulated. 
11.6.4 Kidney biopsy 
 If standard of care kidney biopsies are performed for any reason, at any time-point, e.g. 
suspected rejections, information from the kidney biopsy report will be collected. Data will be 
summary tabulated. 
11.6.5 Number of graft rejection episodes 
The number of graft rejection episodes will be tabulated at 1, 2, 3 and 5 years following Banff 
classification. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
32 (43) 
11.6.6 Treatment of graft rejection episodes 
The treatment of graft rejection episodes will be summary tabulated by 1, 2, 3 and 5 years and 
by treatment type. Examples of treatment types are dialysis episodes, plasmapheresis and 
medication. 
11.6.7 Comorbidity 
Medically relevant comorbidities are e.g. infections, malignancy, diabetes mellitus and 
cardiovascular events. These events will be tabulated at 1, 2, 3 and 5 years by comorbidity type.  
11.6.8 DSA levels 
DSA levels will be evaluated by SAB-HLA at 1, 2, 3 and 5 years. The DSA levels will be 
summary tabulated and presented graphically. 
11.6.9 BK virus 
Presence of BK virus will be tabulated at 1, 2, 3 and 5 years. 
11.6.10 ADA 
ADA will be evaluated by anti-imlifidase IgG at 1, 2, 3 and 5 years. Data will be summary 
tabulated. 
11.6.11 Health related quality of life 
HR-QoL will be evaluated by patient questionnaires EQ-5D-5L and KDQOL at 1, 2, 3 and 5 
years. The individual guidelines for the questionnaires will be followed to create the summary 
tabulations, the details of which will be given in the SAP. 
11.7 
Safety Endpoints 
11.7.1 Analysis of Adverse Events 
Only adverse events related to study procedures or a clinically significant safety lab value will 
be collected. If the lab value is attributable to worsening renal function, rejection, or natural 
progression of disease, it will not be reported as an AE. 
If such events occur, they will be listed. 
11.7.2 Analysis of Safety Variables 
All clinical safety laboratory tests will be tabulated at 1, 2, 3 and 5 years. 
11.8 
Determination of Sample Size 
As this is a non-interventional follow up study, no power calculations for sample size estimation 
were performed. All patients enrolled in the selected previous or ongoing imlifidase kidney 
transplant studies will be considered for inclusion in this study. It is anticipated that 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
33 (43) 
approximately 46 patients could be included, although the exact number will depend on 
enrolment and patients’ discontinuation figures in ongoing and/or selected clinical studies 
 
12. 
CHANGES IN STUDY CONDUCT OR PLANNED ANALYSES 
Any changes and deviations to plans described in the protocol must be documented. 
12.1 
Protocol Amendment(s) 
Any change to this protocol will be documented in a protocol amendment, issued by Hansa 
Biopharma, and agreed upon by the investigator and Hansa Biopharma prior to its 
implementation. Protocol Amendments and documents updated as a result of the Protocol 
Amendment must not be implemented until all approvals (IEC/IRB and Regulatory Authorities, 
if applicable) have been obtained. 
Changes to the protocol to eliminate immediate hazard(s) to study subjects may be implemented 
prior to IEC(s)/IRB(s) and RA approval. 
12.2 
Protocol Deviations 
Under working conditions, deviations from the protocol may occur. If deviations from the 
protocol occur, the investigator must inform the monitor, and the implications of the deviation 
must be reviewed, discussed and documented on the Protocol Deviation Form. Deviation 
reports and supporting documentation will be kept in the investigator site file and the trial 
master file. 
Hansa Biopharma will review all protocol deviations continuously during the course of the 
study and assess whether there is a need to update the protocol through an amendment to avoid 
future deviations. 
Planned protocol deviations are not permitted. 
12.3 
Changes to the Statistical Analysis Plan 
Any changes to the SAP will be described in the Clinical Study Report and/or in the Statistical 
Report. 
12.4 
Premature Termination or Suspension of the Study 
If the study is prematurely terminated or suspended for any reason, the investigator/institution 
should promptly inform the subjects and should assure appropriate therapy and follow up. 
If the investigator terminates or suspends a study without prior agreement of Hansa Biopharma, 
the investigator should inform the institution where applicable. The investigator/institution 
should promptly inform Hansa Biopharma and should provide Hansa Biopharma with a detailed 
written explanation of the termination or suspension. If Hansa Biopharma terminates or 
suspends a study, the investigator should promptly inform the institution where applicable. In 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
34 (43) 
both cases Hansa Biopharma will promptly inform the RA and IEC and provide them with a 
detailed written explanation of the termination or suspension. 
If the RA or IEC terminates or suspends its approval/favorable opinion of a study, Hansa 
Biopharma should inform the investigators and institutions (where applicable) and provide 
them with a detailed written explanation of the termination or suspension. 
13. 
REPORTING AND PUBLICATION 
13.1 
Clinical Study Report 
The results from this study will be reported in a clinical study report (CSR) within one year 
after end of study (section 3.4). This will be prepared by Hansa Biopharma and submitted for 
comments and signature to the signatory investigator(s). 
13.2 
Confidentiality and Data Ownership 
Any confidential information relating to the IMP or the study, including any data and results 
from the study will be the exclusive property of Hansa Biopharma. The investigator and any 
other persons involved in the study will protect the confidentiality of the proprietary 
information belonging to Hansa Biopharma. 
13.3 
Publications  
13.4 
Publication Policy 
At the end of the study, one or more manuscripts for joint publication may be prepared in 
collaboration between the investigator(s) offered authorship and Hansa Biopharma.  
Any external CRO or laboratory involved in the conduct of this study has no publication rights 
regarding the study. 
13.5 
Public disclosure 
The study will be registered in a public clinical trials registry i.e. the U.S. National Institutes of 
Health register ClinicalTrials.gov and/or EU Clinical Trials Register if the study is conducted 
in Europe. 
14. 
ETHICAL AND REGULATORY ASPECTS 
14.1 
Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that have their origins in 
the World Medical Association Declaration of Helsinki, Ethical Principles for Medical 
Research Involving Human Subjects, Brazil 2013 in compliance with the approved protocol 
and applicable regulatory requirements.  

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
35 (43) 
The responsibilities of Hansa Biopharma, the monitor and the investigator are defined in the 
ICH-GCP consolidated guideline (E6 R2) and applicable regulatory requirements in the country 
where the study takes place. The investigator is responsible for adhering to the ICH-GCP 
responsibilities of investigators.  
14.2 
Liabilities and Insurance 
Hansa Biopharma is, as sponsor, responsible for ensuring appropriate general/product liability 
insurance and, as required in accordance with applicable laws and regulations, country-specific 
liability insurance coverage for claims made by a study subject for injury arising from the 
subject’s participation in the study. 
14.3 
Independent Ethics Committee(s) and Institutional Review Boards (IRB) 
All ethical and regulatory approvals must be available before a subject is exposed to any study-
related procedure, including screening tests for eligibility. 
According to applicable regulatory requirements Hansa Biopharma will: 
• 
obtain approval from or notify the relevant (IECs) of the protocol, any amendments, the 
Subject Information Sheet/Informed Consent Form and any advertisements etc. 
• 
send periodic updates to the IEC(s) if applicable 
• 
provide Investigator(s) with an accurate and complete record of all submissions to the 
local IEC. The copies should be filed in the Investigator File. 
Hansa medical will keep an updated list of submission and approval dates of all documents 
submitted to IEC(s). 
14.4 
Regulatory Authority(ies) 
According to applicable regulatory requirements Hansa Biopharma will send required 
documents to the Regulatory Authorities. Hansa Biopharma will keep an audited list of 
submission and approval dates of all documents submitted to RAs. 
14.5 
Subject Information and Informed Consent 
Before any Study-related activities and in agreement with applicable regulatory requirements, 
Investigator must give the subject oral and written information about the Study in a form that 
the subject can understand. Investigator must ensure that the subject is fully informed about the 
aims, procedures, potential risks, any discomforts and expected benefits of the Study. Before 
consenting, the subject must be left with ample time to consider and to pose questions. 
It must be emphasised that participation is voluntary and that the subject has the right to 
withdraw from the Study at any time without prejudice. 
The original, signed Informed Consent Forms must be kept in the Investigator File.  

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
36 (43) 
The subject will receive a copy of the Subject Information and his/her signed Informed Consent 
Form. 
If new information becomes available that may be relevant to the study subject’s willingness to 
continue participation in the study, a new Subject Information and Informed Consent Form will 
be forwarded to the IEC(s)/IRB(s) (and Regulatory Authorities, if required). The study subjects 
will be informed about this new information and re-consent will be obtained. 
14.6 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and 
Hansa Biopharmaand their agents. This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participating 
subjects. 
The study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of Hansa Biopharma. 
The study monitor or other authorized representatives of Hansa Biopharma may inspect all 
documents and records required to be maintained by the investigator, including but not limited 
to medical records (office, clinic, or hospital).  The clinical study site will permit access to such 
records. 
15. 
ARCHIVING 
15.1 
Retention of Clinical Study Site Documentation 
The investigator is responsible for maintaining all the records, which enable the conduct of the 
study at the site to be fully understood, in compliance with ICH-GCP. The study documentation 
including all the relevant correspondence should be kept by the investigator for at least 25 years  
after the completion or discontinuation of the study, if no further instructions are given by Hansa 
Biopharma. 
The investigator is responsible for the completion and maintenance of the confidential subject 
identification code which provides the sole link between named subject source records and 
anonymous CRF data for Hansa Biopharma. The investigator must arrange for the retention of 
this Subject Identification Log and signed Informed Consent Documents for at least 25 years  
after the completion or discontinuation of the study. 
No study site document may be destroyed without prior written agreement between the 
investigator and Hansa Biopharma. Should the investigator elect to assign the study documents 
to another party, or move them to another location, Hansa Biopharma must be notified. If the 
investigator retires and the documents can no longer be archived by the site, Hansa Biopharma 
can arrange having the Investigator File archived at an external archive. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
37 (43) 
15.2 
Trial Master File 
Hansa Biopharma will archive the Trial Master File in accordance with ICH-GCP and 
applicable regulatory requirements. 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
38 (43) 
16. 
REFERENCES 
EMA Guideline on clinical investigation of immunosuppressants for solid organ transplantation, EMA. 
2008. 
Haas, M., A. Loupy, C. Lefaucheur, C. Roufosse, D. Glotz, D. Seron, B. J. Nankivell, P. F. Halloran, R. 
B. Colvin, E. Akalin, N. Alachkar, S. Bagnasco, Y. Bouatou, J. U. Becker, L. D. Cornell, J. P. 
D. van Huyen, I. W. Gibson, E. S. Kraus, R. B. Mannon, M. Naesens, V. Nickeleit, P. Nickerson, 
D. L. Segev, H. K. Singh, M. Stegall, P. Randhawa, L. Racusen, K. Solez, and M. Mengel. 
2018. 'The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T 
cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for 
next-generation clinical trials', Am J Transplant, 18: 293-307. 
Iyer, S. P., L. E. Nikkel, K. K. Nishiyama, E. Dworakowski, S. Cremers, C. Zhang, D. J. McMahon, S. 
Boutroy, X. S. Liu, L. E. Ratner, D. J. Cohen, X. E. Guo, E. Shane, and T. L. Nickolas. 2014. 
'Kidney Transplantation with Early Corticosteroid Withdrawal: Paradoxical Effects at the 
Central and Peripheral Skeleton', J Am Soc Nephrol: 1331-41. 
Montgomery, R. A., A. A. Zachary, L. E. Ratner, D. L. Segev, J. M. Hiller, J. Houp, M. Cooper, L. 
Kavoussi, T. Jarrett, J. Burdick, W. R. Maley, J. K. Melancon, T. Kozlowski, C. E. Simpkins, 
M. Phillips, A. Desai, V. Collins, B. Reeb, E. Kraus, H. Rabb, M. S. Leffell, and D. S. Warren. 
2005. 'Clinical results from transplanting incompatible live kidney donor/recipient pairs using 
kidney paired donation', JAMA, 294: 1655-63. 
Montgomery, R. A., B. E. Lonze, K. E. King, E. S. Kraus, L. M. Kucirka, J. E. Locke, D. S. Warren, C. 
E. Simpkins, N. N. Dagher, A. L. Singer, A. A. Zachary, and D. L. Segev. 2011. 'Desensitization 
in HLA-incompatible kidney recipients and survival', N Engl J Med, 365: 318-26. 
Orandi, B. J., J. M. Garonzik-Wang, A. B. Massie, A. A. Zachary, J. R. Montgomery, K. J. Van 
Arendonk, M. D. Stegall, S. C. Jordan, J. Oberholzer, T. B. Dunn, L. E. Ratner, S. Kapur, R. P. 
Pelletier, J. P. Roberts, M. L. Melcher, P. Singh, D. L. Sudan, M. P. Posner, J. M. El-Amm, R. 
Shapiro, M. Cooper, G. S. Lipkowitz, M. A. Rees, C. L. Marsh, B. R. Sankari, D. A. Gerber, P. 
W. Nelson, J. Wellen, A. Bozorgzadeh, A. O. Gaber, R. A. Montgomery, and D. L. Segev. 2014. 
'Quantifying the risk of incompatible kidney transplantation: a multicenter study', Am J 
Transplant, 14: 1573-80. 
Orandi, B. J., X. Luo, A. B. Massie, J. M. Garonzik-Wang, B. E. Lonze, R. Ahmed, K. J. Van Arendonk, 
M. D. Stegall, S. C. Jordan, J. Oberholzer, T. B. Dunn, L. E. Ratner, S. Kapur, R. P. Pelletier, 
J. P. Roberts, M. L. Melcher, P. Singh, D. L. Sudan, M. P. Posner, J. M. El-Amm, R. Shapiro, 
M. Cooper, G. S. Lipkowitz, M. A. Rees, C. L. Marsh, B. R. Sankari, D. A. Gerber, P. W. 
Nelson, J. Wellen, A. Bozorgzadeh, A. O. Gaber, R. A. Montgomery, and D. L. Segev. 2016. 
'Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors', N Engl J 
Med, 374: 940-50. 
Wenig, K., L. Chatwell, U. von Pawel-Rammingen, L. Bjorck, R. Huber, and P. Sondermann. 2004. 
'Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity 
for IgG', Proc Natl Acad Sci U S A, 101: 17371-6. 
Vincents, B., U. von Pawel-Rammingen, L. Bjorck, and M. Abrahamson. 2004. 'Enzymatic 
characterization of the streptococcal endopeptidase, IdeS, reveals that it is a cysteine protease 
with strict specificity for IgG cleavage due to exosite binding', Biochemistry, 43: 15540-9. 
Vo, A. A., J. Petrozzino, K. Yeung, A. Sinha, J. Kahwaji, A. Peng, R. Villicana, J. Mackowiak, and S. 
C. Jordan. 2013. 'Efficacy, outcomes, and cost-effectiveness of desensitization using IVIG and 
rituximab', Transplantation, 95: 852-8. 
von Pawel-Rammingen, U., B. P. Johansson, and L. Bjorck. 2002. 'IdeS, a novel streptococcal cysteine 
proteinase with unique specificity for immunoglobulin G', EMBO J, 21: 1607-15. 
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
39 (43) 
17. 
APPENDIX 1 
Protocol revision history including Summary of Changes 
 
Protocol 
Version 
Date 
Including 
Amendment 
Type and No. 
Overall Rationale for Changes 
1.0 
03 Apr 2018 
 
    N/A Initial approved protocol 
 
2.0 
20 Jun 2018 
Non-
substantial 
01 
• 
Assessment of Quality of Life Questionnaires 
were changed, it was decided to use two instead 
of three questionnaires.  
• 
Kidney biopsy data will be recorded directly in 
CRF instead of retrieved from the biopsy 
reports.  
• 
Any version of Banff classification can be used 
for classification of acute rejection episodes. 
• 
EudraCT number on first page is removed since 
the study was not submitted to any European 
regulatory authority. 
 
3.0 
27 Sep 2020 
Non -
substantial 
02 
• 
The method of data collection will be changed 
from paper CRF to electronic CRF.  
• 
A study visit can be performed remotely if a 
subject is not able to visit the site.  
• 
Clarify the wordings “acute rejection episode” 
and “DSA rebound” by change wordings to 
“graft rejection episode”. 
• 
Clarify that creatinine and proteinuria results 
from graft rejection episodes will be collected as 
well as from the time for planned 1- and 2-Years 
visits if study start was after those visits should 
have taken place. 
4.0 
22 NOV 2021 
Non-
substantial 
03 
• 
Updates due to change in CRO responsible for 
SAE and SUSAR handling. 
 
 
 
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
40 (43) 
Protocol AMENDMENT NUMBER 03 Summary: 
AMENDMENT TYPE: 
This amendment is considered to be non-substantial because it neither significantly impacts 
the safety or physical/mental integrity of participants nor the scientific value of the trial. 
RATIONALE FOR THE AMENDMENT: 
The protocol is amended in response to a change in the CRO responsible for the SAE and 
SUSAR handling. 
AMENDED SECTIONS IN THE PROTOCOL: 
Details of the changes to the protocol are shown below. Changes to the text are shown in 
strike through text and new text in underlined italics. The sections refer to the study protocol 
Final Version 3.0 including Amendment 02, dated 27 SEP 2020. 
 
1 
CHANGE OF CRO RESPONSIBLE FOR SAE/SUSAR REPORTING 
Rationale 
The CRO handling the SAE and SUSAR reporting have been replaced.  
1.1 
Amended Section  
Section 8.2.5, Reporting of Serious Adverse Events 
Changed from 
--- 
An assigned contract research organisation (Drug Safety Navigator, DSN) will be responsible 
for reporting all SAEs to Regulatory Authorities (RA) in accordance with International 
Conference on Harmonisation, Good Clinical Practice (GCP) and local regulations.  
As soon as the Investigator is aware of a potential SAE he/she should contact DSN by e-mail 
no later than 24 hours after the knowledge of such a case. At the time of initial reporting the 
investigator must provide as a minimum requirement, subject number, birth date, description 
of the SAE and a preliminary assessment of causality.  
 
Contact Information: 
CRO: 
Drug Safety Navigator (DSN) 
e-mail: 
  
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
41 (43) 
For fatal or life-threatening adverse events where important or relevant information is 
missing, active follow up is undertaken immediately. Investigators or other site personnel 
inform Hansa Biopharma and monitor of any follow up information on a previously reported 
SAE immediately but no later than within 24 hours of when he or she becomes aware of it. 
The monitor or Hansa Biopharma will advise the investigator/study site personnel how to 
proceed. 
The SAE reporting procedures are detailed in the study specific Safety Management Plan. 
This plan is an agreement between the Hansa Biopharma, and DSN. 
 
Changed to 
--- 
An assigned contract research organisation (Drug Safety Navigator, DSN Primevigilance) 
will be responsible for reporting all SAEs to Regulatory Authorities (RA) in accordance with 
International Conference on Harmonisation, Good Clinical Practice (GCP) and local 
regulations.  
As soon as the Investigator is aware of a potential SAE he/she should contact DSN 
Primevigilance by e-mail no later than 24 hours after the knowledge of such a case. At the 
time of initial reporting the investigator must provide as a minimum requirement, subject 
number, birth date, description of the SAE and a preliminary assessment of causality.  
 
Contact Information: 
CRO: 
Drug Safety Navigator (DSN) Primevigilance 
e-mail: 
  
 
For fatal or life-threatening adverse events where important or relevant information is 
missing, active follow up is undertaken immediately. Investigators or other site personnel 
inform Hansa Biopharma and monitor of any follow up information on a previously reported 
SAE immediately but no later than within 24 hours of when he or she becomes aware of it. 
The monitor or Hansa Biopharma will advise the investigator/study site personnel how to 
proceed. 
The SAE reporting procedures are detailed in the study specific Safety Management Plan. 
This plan is an agreement between the Hansa Biopharma, and DSN Primevigilance. 
 
1.2 
Amended Section  
Section 8.2.6, Reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
42 (43) 
Changed from 
--- 
SUSARs with an outcome of death or which are life threatening must be reported to the 
relevant RAs within 7 calendar days, all other SUSARs must be submitted within 15 calendar 
days. The SUSAR reporting procedures are detailed in the study Safety Management Plan. 
This plan is an agreement between the Hansa Biopharma, and Drug Safety Navigator. Hansa 
Biopharma will notify the appropriate RA(s) and all participating study investigators of any 
SUSARs on an expedited basis and in accordance with applicable regulations. In addition, 
Hansa Biopharma is responsible for informing all investigators in all other ongoing studies 
involving imlifidase about all SUSARs.  
--- 
 
Changed to 
--- 
SUSARs with an outcome of death or which are life threatening must be reported to the 
relevant RAs within 7 calendar days, all other SUSARs must be submitted within 15 calendar 
days. The SUSAR reporting procedures are detailed in the study Safety Management Plan. 
This plan is an agreement between the Hansa Biopharma, and Drug Safety Navigator 
Primevigilance. Hansa Biopharma will notify the appropriate RA(s) and all participating 
study investigators of any SUSARs on an expedited basis and in accordance with applicable 
regulations. In addition, Hansa Biopharma is responsible for informing all investigators in all 
other ongoing studies involving imlifidase about all SUSARs.  
--- 
 
1.3 
Amended Section  
Section 8.4, Pregnancy and Pregnancy Outcome 
Changed from 
--- 
If a subject becomes pregnant during the current study, the subject will continue in the study 
according to study protocol, if possible. A Pregnancy Report Form must be sent by the 
investigator to Drug Safety Navigator at the latest within two weeks of learning of the 
pregnancy. The outcome of all pregnancies (spontaneous miscarriage, elective termination, 
normal birth or congenital abnormality) will be followed up on the Pregnancy Report Form 
even after the subject has completed or discontinued the study. Drug Safety Navigator will 
follow up on pregnancy outcome 4 weeks after the projected due date. 
--- 
 

HansaBiopharma 
Date: 
22 NOV 2021 
Project:  IdeS transplantation 
   Version: 
4.0 incl. Amend 03 
Clinical Trial Protocol No: 17-HMedIdeS-14 
Doc No.:   2018-002 
 
43 (43) 
Changed to 
--- 
If a subject becomes pregnant during the current study, the subject will continue in the study 
according to study protocol, if possible. A Pregnancy Report Form must be sent by the 
investigator to Drug Safety Navigator Primevigilance at the latest within two weeks of 
learning of the pregnancy. The outcome of all pregnancies (spontaneous miscarriage, elective 
termination, normal birth or congenital abnormality) will be followed up on the Pregnancy 
Report Form even after the subject has completed or discontinued the study. Drug Safety 
Navigator Primevigilance will follow up on pregnancy outcome 4 weeks after the projected 
due date. 
---