A Prospective, Observational Long-term Follow-up Trial of Kidney Transplant Patients Treated With Imlifidase or Plasma Exchange After an Active/Chronic Active Antibody-Mediated Rejection Episode
Conditions: Kidney Transplant Rejection
Sponsor: Hansa Biopharma AB

Hansa Biopharma AB 
Date: 22-NOV-2021  
Project: AMR 
Version: 1.1 
Clinical Trial Protocol No.: 20-HMedIdeS-18 
Doc. No.: 2020-059 
 
 
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Clinical Trial Protocol 
 
A prospective, observational long-term follow-up trial of kidney transplant patients treated 
with imlifidase or plasma exchange after an active/chronic active Antibody-Mediated 
Rejection episode  
 
Clinical Trial Protocol No.: 
20-HMedIdeS-18 
Protocol version and date: 
1.1, 22-NOV-2021 
Investigational Medicinal Product: 
N/A 
Phase: 
Long-term prospective follow-up trial 
Proposed indication: 
Active/chronic active Antibody-Mediated 
Rejection 
Coordinating investigator: 
 
EudraCT No.: 
2020-004777-49 
IND No.: 
128074 
Name and Address of Sponsor: 
Hansa Biopharma AB 
P.O. Box 785 
SE-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No unpublished information contained herein may be disclosed without prior written approval 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.  
 

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Signature page 
This protocol version includes Non-Substantial Amendment. No. 01. According to Hansa 
Biopharma’s SOP, only the responsible CRM approves this type of amendments by signing 
the “Hansa Biopharma AB Approval of Non-Substantial Amendment to Protocol “-form.  
It is referred to the previous protocol (version 1.0, 02-OCT-2020) for approvals by Hansa 
Biopharma’s signatories and the signatory coordinating principal investigator. 
 
 
 

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Investigators and Clinical Trial Administrative Structure 
Coordinating 
Name and title: 
Address: 
 
 
 
 
Phone 
E-mail 
 
 
 
 
 
 
 
 
 
 
Sponsor’s Senior 
Medical Director 
Name and title: 
 
Address: 
 
Phone: 
E-mail: 
 
 
Hansa Biopharma AB, P.O. BOX 785, 
SE- 220 07, Lund, Sweden 
 
 
 
 
Contact details for all investigators responsible for conducting the trial, medically qualified 
physicians responsible for all trial site related medical decisions (if other than the 
investigators), clinical laboratories, other medical and/or technical departments and/or 
institutions involved in the trial, monitors, and relevant sponsor representatives are supplied in 
a trial contact list filed in the investigator site file/trial master file. 
 
 
 

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Synopsis 
Name of Sponsor/Company 
Hansa Biopharma AB (hereafter referred to as Hansa Biopharma) 
Title of the Trial 
A prospective, observational long-term follow-up trial of kidney transplant patients treated 
with imlifidase or plasma exchange after an active/chronic active Antibody-Mediated 
Rejection (AMR) episode  
Co-ordinating Investigator  
 
Trial Sites 
All sites, approximately 8-11 sites, in US, Europe and Australia, that have participated in 
trial 16-HMedIdeS-12 will be asked to participate.  
Planned trial period 
First subject first visit (FSFV) OCT/2020 
Last subject last visit (LSLV) 3 years (+/- 4 months) 
after last subject’s first visit in feeder trial 
Clinical Phase  
Long-term prospective follow-up 
trial 
Background and Scientific Justification for Conducting the Trial 
The aim of this trial is to collect data and provide a better understanding of the long-term 
outcome of imlifidase treatment on active or chronic active AMR in kidney transplant 
recipients. This is met by collecting data during extended follow up at 1, 2, and 3 years after 
treatment with either imlifidase or plasma exchange in trial 16-HMedIdeS-12. Data for 
parameters such as kidney graft survival, patient survival, kidney function, treatment of 
rebound of DSA and anti-drug antibodies will be collected. 

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Objectives 
The primary objective of this trial is to evaluate kidney graft survival in subjects that have 
been treated with imlifidase or plasma exchange in association with AMR in trial 
16-HMedIdeS-12 (referred to as the feeder trial). 
Secondary objective(s) are to: 
• Evaluate overall graft survival at Year 1 and 2 
• Evaluate patient survival at Year 3  
• Evaluate kidney function at Year 1, 2 and 3 
• Evaluate DSA levels at Year 1, 2 and 3 
• Evaluate anti-imlifidase IgG levels at year 1, 2 and 3 after  
• Investigate the occurrence of AMR episodes after completed the feeder trial 
(classified according to Banff 2017 (Haas et al. 2018) or later version) 
• Investigate the occurrence of other graft rejection episodes (classified according to 
Banff 2017 or later version)  
 
Endpoints: 
The primary endpoint of this trial is the overall graft survival, evaluated at Year 3. 
Secondary endpoints of this trial are:  
• 
Overall graft survival evaluated at Year 1 and 2 
• Patient survival, evaluated at 3 years after start of treatment in feeder trial  
• Kidney function, as evaluated by eGFR, S/P-creatinine and albumin/creatinine ratio 
in urine at 1, 2, and 3 years after start of treatment in feeder trial  
• Proportions of subjects with presumed or biopsy proven AMR episodes (classified 
according to Banff 2017 or later version) within 3 years after start of treatment in 
feeder trial  
• Proportion of subjects with presumed or biopsy-proven rejection episodes, (other than 
AMR episodes) classified according to Banff 2017 or later version) up to 3 years after 
start of treatment in feeder trial 
• DSA levels at 1, 2, and 3 years after start of treatment in feeder trial  
• Anti-imlifidase IgG at 1, 2, and 3 years after start of treatment in feeder trial 
 
Methodology 
This is an observational 3-year follow up trial. The trial will primarily evaluate kidney graft 
survival in subjects with active or chronic active AMR treated with imlifidase or plasma 
exchange. Subjects that have participated in trial 16-HMedIdeS-12 (called the feeder trial) 
will be asked to participate. The subjects will attend three follow up visits 1, 2, and 3 years 
after start of treatment in the feeder trial. 

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Trial Procedures/Assessments 
At all visits, graft survival and information about graft rejection episodes will be assessed. 
Blood samples for graft function (creatinine and eGFR), and analysis of DSA and ADA will 
be collected as well as a urine sample for albumin/creatinine ratio. Information about patient 
survival and comorbidity (infections, malignancy, diabetes mellitus, cardiovascular events 
and comorbidity leading to worsening of kidney function) will be recorded. 
Number of subjects 
Up to 30 subjects will be included.  
Diagnosis and main criteria for inclusion/exclusion  
Inclusion criteria: 
• Signed Informed Consent obtained before any trial-related procedures 
• Willingness and ability to comply with the protocol 
• Previous treatment with imlifidase or plasma exchange in trial 16-HMedIdeS-12 
Exclusion criteria: 
• Inability by the judgement of the investigator to participate in the trial for any other 
reason 
Medicinal Product(s) 
Not applicable 
Duration of treatment  
Each subject will be followed up 1, 2, and 3 years after start of treatment in feeder trial. 
Statistical methods 
This is a long-term observational trial and for the evaluation and presentation of data 
descriptive techniques will be used. The data from the clinical assessments will be 
summarized by time point and treatment group in the feeder trial. 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, overall graft survival will be evaluated and 
presented with Kaplan-Meier curves. There will be no formal statistical hypothesis or testing 
because of the observational nature of the trial. Since this is a long-term follow up trial to the 
16-HMedIdeS12 trial, no sample size and associated power calculations has been made.  
 
 
 

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Protocol Revision History including Summary of Changes 
Protocol 
Version 
Date 
Including 
Amendment 
Type and No. 
Overall Rationale for Changes 
1.1 
22-NOV-2021 
Non-
substantial 
amendment 
No. 01 
• 
Change in CRO responsible for 
SAE/SUSAR reporting 
1.0 
02-OCT-2020 
N/A 
Initially approved protocol 
 
See Appendix 1 “Clinical Study Protocol Amendment” for details of Amendment No. 01. 

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Table of Contents 
Signature page ...................................................................................................................... 2 
Investigators and Clinical Trial Administrative Structure .............................................. 3 
Synopsis ................................................................................................................................. 4 
Protocol Revision History including Summary of Changes ............................................. 7 
Table of Contents ................................................................................................................. 8 
List of Abbreviations .......................................................................................................... 12 
1. 
Introduction .......................................................................................................... 13 
1.1 
Background ............................................................................................................ 13 
1.2 
Scientific Rationale ................................................................................................ 14 
1.3 
Benefit/Risk Assessment ........................................................................................ 14 
2. 
Trial Objectives and Endpoints .......................................................................... 15 
2.1 
Objectives ............................................................................................................... 15 
2.1.1 
Primary Objective .................................................................................................. 15 
2.1.2 
Secondary Objectives ............................................................................................. 15 
2.2 
Endpoints ............................................................................................................... 15 
2.2.1 
Primary Endpoint ................................................................................................... 15 
2.2.2 
Secondary Endpoints .............................................................................................. 15 
3. 
Investigational Plan .............................................................................................. 16 
3.1 
Overall Trial Design ............................................................................................... 16 
3.1.1 
Medical monitoring ................................................................................................ 16 
3.1.2 
Interim Analysis ..................................................................................................... 16 
3.2 
Trial Schedule ........................................................................................................ 17 
3.3 
Planned Number of Trial Sites and Subjects ......................................................... 17 
3.4 
End-of-Trial ........................................................................................................... 17 
4. 
Trial Population ................................................................................................... 18 
4.1 
Eligibility Criteria .................................................................................................. 18 
4.2 
Inclusion Criteria .................................................................................................... 18 
4.3 
Exclusion Criteria .................................................................................................. 18 
4.4 
Restrictions ............................................................................................................. 18 
4.4.1 
Prohibited Therapy ................................................................................................. 18 
4.5 
Discontinuation of Subjects ................................................................................... 18 
5. 
Trial Treatment .................................................................................................... 19 

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5.1 
Concomitant Medications and Therapies ............................................................... 19 
6. 
Trial Procedures ................................................................................................... 19 
6.1 
Trial Visits .............................................................................................................. 19 
6.1.1 
Screening ................................................................................................................ 19 
6.1.2 
Year 1, Year 2, and Year 3 (End-of-Trial) ............................................................. 20 
6.2 
Flow Chart .............................................................................................................. 21 
7. 
Trial Assessments ................................................................................................. 22 
7.1 
Assessments related to Primary Endpoint .............................................................. 22 
7.2 
Assessments related to Secondary Endpoints ........................................................ 22 
7.2.1 
Overall graft survival at Years 1 and 2 .................................................................. 22 
7.2.2 
Patient survival ....................................................................................................... 22 
7.2.3 
Kidney function ...................................................................................................... 22 
7.2.4 
AMR rejection episodes and Graft rejection episodes (other than AMR 
episodes) ................................................................................................................. 22 
7.2.5 
Donor-specific antibody (DSA) levels ................................................................... 22 
7.2.6 
Immunogenicity by Anti-Drug Antibodies (ADA) ................................................ 23 
7.2.7 
Comorbidity ........................................................................................................... 23 
7.2.8 
Demographics ........................................................................................................ 23 
8. 
Biological Sampling Procedures ......................................................................... 23 
8.1 
Volume of Blood .................................................................................................... 23 
8.2 
Handling, Storage and Destruction of Biological Samples .................................... 23 
8.3 
Chain of Custody of Biological Samples ............................................................... 23 
8.4 
Withdrawal of Informed Consent for Biological Samples ..................................... 24 
9. 
Adverse Events and Serious Adverse Events .................................................... 25 
9.1 
Definitions .............................................................................................................. 25 
9.1.1 
Adverse Event ........................................................................................................ 25 
9.1.2 
Serious Adverse Event ........................................................................................... 25 
9.2 
Collection and Recording of Adverse Events ........................................................ 26 
9.2.1 
Variables ................................................................................................................ 26 
9.2.1.1 Causality Assessment ............................................................................................. 26 
9.2.2 
Adverse Events Based on Signs and Symptoms .................................................... 26 
9.2.3 
Follow-up of Unresolved Adverse Events ............................................................. 26 
9.2.4 
Reporting of Serious Adverse Events .................................................................... 27 
9.2.5 
Reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) ........ 27 

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9.3 
Pregnancy and Pregnancy Outcome....................................................................... 28 
10. 
Trial Management ................................................................................................ 29 
10.1 
Pre-Trial Activities ................................................................................................. 29 
10.2 
Monitoring of the Trial .......................................................................................... 29 
10.3 
Source Data ............................................................................................................ 29 
10.4 
Audit and Inspection .............................................................................................. 30 
10.5 
Trial Agreements .................................................................................................... 30 
11. 
Data Management ................................................................................................ 31 
11.1 
Case Report Form .................................................................................................. 31 
11.2 
Provider of Data Management ............................................................................... 31 
11.3 
Coding .................................................................................................................... 31 
11.4 
Handling of External Data ..................................................................................... 31 
12. 
Statistical Methods ............................................................................................... 32 
12.1 
Analysis Sets .......................................................................................................... 32 
12.1.1 
Full Analysis Set (FAS) ......................................................................................... 32 
12.2 
Subject Characteristics ........................................................................................... 32 
12.2.1 
Subject Disposition ................................................................................................ 32 
12.2.2 
Demographics and Other Baseline Characteristics ................................................ 32 
12.2.3 
Recent and Concomitant Medication ..................................................................... 32 
12.3 
Statistical Analysis of Primary Endpoints ............................................................. 32 
12.3.1 
Primary efficacy analysis ....................................................................................... 33 
12.4 
Statistical Analysis of Secondary Endpoints ......................................................... 33 
12.4.1 
Graft survival at Year 1 and 2 ................................................................................ 33 
12.4.2 
Patient survival ....................................................................................................... 33 
12.4.3 
Kidney function ...................................................................................................... 33 
12.4.4 
Proportion of subjects with rejection episodes ...................................................... 33 
12.4.5 
DSA level at 1, 2, and 3 years after start of treatment in feeder trial ..................... 33 
12.4.6 
Immunogenicity ..................................................................................................... 34 
12.5 
Analysis of Adverse Events ................................................................................... 34 
12.6 
Determination of Sample Size ............................................................................... 34 
13. 
Changes in Trial Conduct or Planned Analyses ............................................... 34 
13.1 
Protocol Amendment(s) ......................................................................................... 34 
13.2 
Protocol Deviations ................................................................................................ 34 

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13.3 
Statistical Analysis Plan ......................................................................................... 35 
13.4 
Premature Termination or Suspension of the Trial ................................................ 35 
14. 
Reporting and Publication .................................................................................. 35 
14.1 
Clinical Trial Report .............................................................................................. 35 
14.2 
Confidentiality and Data Ownership ...................................................................... 35 
14.3 
Publications ............................................................................................................ 35 
14.3.1 
Publication Policy .................................................................................................. 35 
14.4 
Public Disclosure ................................................................................................... 36 
15. 
Ethical and Regulatory Aspects .......................................................................... 36 
15.1 
Ethical Conduct of the Trial ................................................................................... 36 
15.2 
Liabilities and Insurance ........................................................................................ 36 
15.3 
Independent Ethics Committee(s) and Institutional Review Board(s) ................... 36 
15.4 
Regulatory Authority(ies) ...................................................................................... 37 
15.5 
Subject Information and Informed Consent ........................................................... 37 
15.6 
Subject Confidentiality .......................................................................................... 37 
16. 
Archiving ............................................................................................................... 38 
16.1 
Retention of Clinical Trial Site Documentation .................................................... 38 
16.2 
Trial Master File ..................................................................................................... 38 
17. 
References ............................................................................................................. 39 
18. 
APPendix 1 ............................................................................................................ 40 
18.1 
Protocol Amendment 01 ........................................................................................ 40 
 
List of Tables 
Table 1. 
Summary table of clinical studies with imlifidase showing rapid effect on 
anti-HLA antibodies/DSA. ........................................................................... 14 
Table 2. 
Flow chart. .................................................................................................... 21 
 
List of Figures  
Figure 1. 
Overall trial design. ...................................................................................... 16 
 
 
 

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List of Abbreviations 
ABMR 
Antibody-mediated rejection 
ADA 
Anti-drug antibody 
AE 
Adverse event 
AMR 
Antibody-mediated rejection 
CKD 
Chronic kidney disease 
eCRF 
Electronic Case report form 
CRO 
Contract research organisation 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSA 
Donor-specific antibodies 
EMA 
European Medicines Agency 
EOT 
End of Trial 
F(ab’)2 
Antigen-binding fragments (two) of IgG linked by cysteine-bridge(s) 
FDA 
The Food and Drug Administration 
GCP 
Good clinical practice 
eGFR 
Estimated glomerular filtration rate 
HLA 
Human leukocyte antigen 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IdeS 
Immunoglobulin G degrading enzyme of Streptococcus pyogenes 
IEC 
Independent ethics committee 
Ig 
Immunoglobulin 
Imlifidase 
Immunoglobulin G-degrading enzyme of Streptococcus pyogenes, previously 
named HMED-IdeS or IdeS 
IMP 
Investigational medicinal product 
IRB 
Institutional review board 
MedDRA 
The Medical Dictionary for Regulatory Activities 
MFI 
Mean fluorescence intensity 
N/A 
Not applicable 
RA 
Regulatory authority 
S/P- 
Serum/plasma- 
SAB-HLA 
Single antigen bead assay 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SDV 
Source document verification 
SUSAR 
Suspected unexpected serious adverse reaction 
TMF 
Trial master file 

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1. INTRODUCTION 
1.1 Background  
Antibody-mediated rejection (AMR) is one of the most challenging adverse events following 
kidney transplantation and a major cause of graft dysfunction and graft loss. AMR is triggered 
by donor-specific antibodies (DSA). DSA specifically target Human leukocyte antigen (HLA) 
molecules expressed by the transplant endothelium and cause complement-mediated damage 
and microvascular inflammation. Over time, features of chronic injury develop, e.g. transplant 
glomerulopathy. Transplant glomerulopathy is a known consequence of persistent DSA 
positivity which results in graft failure and return to dialysis with attendant consequences for 
the patient and financial costs for the health care system (Gloor et al. 2008; Jordan et al. 2010; 
Lefaucheur et al. 2010; Port et al. 1993; Reinsmoen et al. 2008; OPTN 2012). 
The time duration from the transplantation to the onset of clinical symptoms of AMR varies 
largely between individuals. The difference in time course of development of clinical 
symptoms of AMR might partly depend on whether the targeted HLA molecule has been 
previously encountered by the transplant recipient or not. An early AMR (< 30 days post-
transplant) is commonly classified as active AMR and most often triggered by an 
immunological recall response with pre-existing DSA. A late AMR (> 30 days post-
transplant) is classified as either active or chronic active AMR and is caused by either a recall 
DSA response or newly developing naïve immune response associated with de novo DSA 
production (Schinstock et al. 2020).  
Therapies for AMR are limited (Sellares et al. 2012). Currently used therapies include high 
dose IVIg +/- rituximab, plasma exchange with low dose IVIg +/- rituximab, eculizumab, and 
a minimal experience with bortezomib. However, no therapy is currently approved, and 
patients are often treated with combination therapies that make analysis of efficacy of any one 
agent difficult. Thus, there is a large unmet clinical need for new therapies to treat AMR. 
Imlifidase is an IgG-degrading enzyme of Streptococcus pyogenes that cleaves all four human 
subclasses of IgG with high efficacy and strict specificity. Cleavage of IgG generates one 
F(ab’)2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities 
of IgG, including complement activation and Fc receptor binding. The rapidity of the IgG 
cleavage by imlifidase is considered a major advantage as compared with plasma exchange, 
which often requires several rounds over several days to achieve a sufficient DSA reduction. 
Within a few hours after dosing, the entire pool of IgG is fully cleaved into F(ab’)2 and Fc 
fragments thereby creating a window where IgG levels are kept very low for approximately 
one week. Previous clinical trials supporting the rapid elimination of anti-HLA antibodies by 
imlifidase are summarized in Table 1. 
The short-term efficacy and safety of imlifidase in active and chronic active AMR is currently 
being investigated in an ongoing randomized, open-label, multi-centre trial, using plasma 
exchange as active control (16-HMedIdeS-12). A total of 30 subjects will be included, 20 in 
the imlifidase arm and 10 in the plasma exchange arm. In brief, the primary objective is to 
investigate the efficacy of imlifidase in removing DSA in patients who are experiencing an 

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AMR episode after kidney transplantation. Key efficacy outcome measures such as kidney 
function and graft survival will be followed as secondary endpoints, as will DSA levels, up to 
180 days after treatment. 
While a rapid removal of DSA by imlifidase might be expected, DSA is likely to rebound 
unless well-controlled by concomitant immunosuppressive therapy. Therefore, there is a need 
to also address the long-term benefit of imlifidase in AMR. 
Table 1. 
Summary table of clinical studies with imlifidase showing rapid effect on anti-
HLA antibodies/DSA. 
Trial No. / 
EudraCT No./ 
IND No. 
Phase / 
Subjects 
Main objectives 
13-HMedIdeS-02 / 
2013-005417-13  
II / 
Patients with 
CKD 
N= 8 
Efficacy in patients with CKD defined as imlifidase dosing scheme 
resulting in HLA antibody levels acceptable for transplantation, within 
24 h from dosing. 
Safety in the transplantation setting. 
 
13-HMedIdeS-03 / 
2014-000712-34  
II / 
Patients  
N=10 
Safety in the transplantation setting.  
Efficacy defined as HLA antibody levels acceptable for transplantation. 
14-HMedIdeS-04 / 
EudraCT: NA 
IND 124301 
(Investigator 
initiated trial)  
II / 
Patients  
N=17 
 
Safety in combination with Cedars Sinai’s “standard protocol” for 
desensitization of highly sensitized patients. Efficacy in prevention of 
ABMR. 
15-HMedIdeS-06 / 
2016-002064-13 
IND: 128074 
II / 
Patients  
N=19 
Efficacy in creating a negative crossmatch test.  Safety in the 
transplantation setting. 
1.2 Scientific Rationale 
The aim of this trial is to collect data and provide a better understanding of the long-term 
outcome of imlifidase treatment on active or chronic active AMR in kidney transplant 
recipients. This is met by collecting data during extended follow up at 1, 2, and 3 years after 
start of treatment with either imlifidase or plasma exchange in trial 16-HMedIdeS-12. Data 
for parameters such as kidney graft survival, patient survival, kidney function, treatment of 
rebound of DSA and anti-drug antibodies will be collected. 
1.3 Benefit/Risk Assessment 
The subjects included in this trial have been treated with imlifidase or plasma exchange in the 
feeder trial. The current trial is performed to collect long-term follow up data on graft 
function. No IMP will be administered in this trial. 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 be exposed to any additional risk.  

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2. TRIAL OBJECTIVES AND ENDPOINTS 
2.1 Objectives 
2.1.1 Primary Objective 
The primary objective of this trial is to evaluate kidney graft survival in subjects that have 
been treated with imlifidase or plasma exchange in association with AMR in the trial 
16-HMedIdeS-12 (referred to as the feeder trial). 
2.1.2 Secondary Objectives 
The secondary objectives of this trial are to: 
• Evaluate overall graft survival at Year 1 and 2 
• Evaluate patient survival at Year 3  
• Evaluate kidney function at Year 1, 2 and 3 
• Evaluate DSA levels at Year 1, 2 and 3 
• Evaluate anti-imlifidase IgG levels at Year 1, 2 and 3 
• Investigate the occurrence of AMR episodes after completion of the feeder trial 
(classified according to Banff 2017 (Haas et al. 2018) or later version) 
• Investigate the occurrence of other graft rejection episodes (classified according to 
Banff 2017 or later version)  
2.2 Endpoints  
2.2.1 Primary Endpoint 
The primary endpoint of this trial is the overall graft survival, evaluated at Year 3 
2.2.2 Secondary Endpoints 
Secondary endpoints of this trial are:  
• 
Overall graft survival evaluated at Year 1 and 2 
• Patient survival, evaluated at 3 years after start of treatment in feeder trial  
• Kidney function, as evaluated by eGFR, S/P-creatinine and albumin/creatinine ratio in 
urine at 1, 2, and 3 years after start of treatment in feeder trial  
• Proportions of subjects with presumed or biopsy proven AMR episodes (classified 
according to Banff 2017 or later version) within 3 years after start of treatment in 
feeder trial  
• Proportion of subjects with presumed or biopsy-proven rejection episodes, (other than 
AMR episodes) (classified according to Banff 2017 or later version) up to 3 years after 
start of treatment in feeder trial 
• DSA levels at 1, 2, and 3 years after start of treatment in feeder trial  
• Anti-imlifidase IgG at 1, 2, and 3 years after start of treatment in feeder trial 

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3. INVESTIGATIONAL PLAN 
3.1 Overall Trial Design  
This is an observational 3-year follow up trial. Trial sites that have participated, or are 
currently participating, in trial 16-HMedIdeS-12 (the “feeder trial”) will be contacted and 
requested to approach subjects for enrolment in the trial. Up to 30 subjects will be included 
depending on subjects’ willingness to participate in the trial. Subjects who lose their graft 
during the feeder trial or in the intermediate time before being able to enter this trial will not 
continue in the trial but information about the graft loss will be collected. 
The trial will primarily evaluate graft survival. The subjects will attend 3 follow up visits 1, 2 
and 3 years after start of treatment in the feeder trial. Signing of Informed Consent may be 
performed any time between last visit in the feeder trial and up to first visit in the follow up 
trial.  
Kidney function and patient survival will be assessed. Graft rejection episodes will be 
determined using classification according to Banff 2017 or later version. Information from 
kidney biopsies performed within standard of care will be collected. Blood samples for 
analysis of DSA and ADA will be collected at each visit. Medically relevant comorbidity 
(infections, malignancy, diabetes mellitus, cardiovascular events and comorbidity leading to 
worsening of kidney function), will be recorded. Information about treatments of graft 
rejection episodes will be recorded (e.g. plasma exchange and IVIg) as well as creatinine-
level and DSA data conducted within standard of care due to the graft rejection episode. 
If a planned visit cannot be performed, subjects may be contacted by phone and assessments 
described in this protocol may be collected from a local laboratory.  
The overall trial outline is summarized in Figure 1.  
 
Figure 1. 
Overall trial design. 
3.1.1 Medical monitoring 
Medical monitoring will be performed at an interval described in the Medical monitoring 
plan. 
3.1.2 Interim Analysis 
No interim analysis is planned but reports may be created if judged needed. 

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3.2 Trial Schedule 
The first subject first visit is planned in October 2020, 1 year after first subject was treated in 
the feeder trial. 
Last subject last visit in this trial will be 3 years (+/- 4 months) after last subject’s first visit in 
the feeder trial.  
3.3 Planned Number of Trial Sites and Subjects 
All sites included in the feeder trial, approximately 14 sites, in US, Europe and Australia, will 
be asked to participate, and up to 30 subjects may be included.  
3.4 End-of-Trial 
The planned End-of-Trial is defined as last subject last visit. Hansa Biopharma will ensure 
that an End-of-Trial Notification is submitted to the concerned health authority and IEC/IRB 
according to local requirements. 
For procedures in case of premature termination or suspension of the Trial, see Section 13.4. 
 
 

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4. TRIAL POPULATION 
4.1 Eligibility Criteria 
Subjects who have been treated with imlifidase or plasma exchange in the feeder trial may be 
included. The subjects will be approached, and informed consent will be obtained for 
participation in the current trial.  
The investigator will maintain a screening log to record details of all subjects screened and to 
confirm eligibility or record reasons for screening failure, as applicable. Confirmed eligibility 
or reasons for screening failure will be recorded in the eCRF. 
4.2 Inclusion Criteria 
• Signed Informed Consent obtained before any trial-related procedures 
• Willingness and ability to comply with the protocol 
• Previous treatment with imlifidase or plasma exchange in the trial 16-HMedIdeS-12 
Note: The primary objective of this trial is overall graft survival after treatment with 
imlifidase or plasma exchange. Therefore, subjects can also be included even if the subject 
did not fully complete the feeder trial follow up but was dosed with imlifidase or plasma 
exchange in the trial 16-HMedIdeS-12. 
4.3 Exclusion Criteria 
• Inability by the judgement of the investigator to participate in the trial for any other reason 
4.4 Restrictions 
4.4.1 Prohibited Therapy 
Subjects will continue with their prescribed therapies (drugs or procedures) during the trial.   
4.5 Discontinuation of Subjects  
The subjects have the right to withdraw from the trial at any time for any reason, without the 
need to justify their decision. However, the investigator should record the reason and date for 
the subject’s withdrawal, if possible. The investigator also has the right to withdraw subjects. 
In either event, the investigator must notify the Monitor. 
A subject that prematurely discontinues participation will, if possible, be called in for an End-
of-Trial Visit (as defined in Visit Procedures, Section 6.1.2). Even if the subject is not able to 
attend, the End-of-Trial Form must be completed. 
 
 

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5. TRIAL TREATMENT 
No IMP will be administered in this trial. 
5.1 Concomitant Medications and Therapies 
Only immunosuppressive medications will be recorded in the concomitant medication module 
in the eCRF throughout the trial, beginning from screening to end of trial. Medication and 
therapies to treat recurrent AMR episodes will be recorded in the eCRF. 
Recorded information will include indication, name of drug, route of administration and start 
and stop date.  
6. TRIAL PROCEDURES 
6.1 Trial Visits  
The flow chart of all trial visits, including applicable visit windows, is provided in 
Section 6.2. A list of scheduled activities/assessments for each visit is provided in 
Sections 6.1.1 to 6.1.2 and further details of how each activity/assessment is to be performed 
is given in the subsections to Section 7. 
All subjects considered for the trial must be informed about the trial, verbally and in writing, 
and give their written consent before any trial procedure is performed.  
Informed consent may be signed at the last visit in the feeder trial. For each subject, the 
duration of the trial, including the time from signing informed consent to end of trial will not 
exceed 3 years and 10 months. This includes 6 months if informed consent is signed at the 
end of trial in feeder trial and the visit window of 4 months at Year 3 visit.  
If a subject is not able to attend a planned visit, the subject may be contacted by phone and 
assessments described in this protocol may be collected from a local laboratory. 
6.1.1 Screening  
Screening may be conducted at the earliest at the last visit in feeder trial and at the latest at 
Year 1 (one year after start of treatment in feeder trial +/- the visit window of 2 months).  
The following assessments and activities will be performed: 
• Check inclusion and exclusion criteria  
• Sign informed consent, see section 15.5 
• Assessment of graft survival. For subjects with graft loss after last visit in the feeder 
trial, date, reason for graft loss, medical history, and root cause will be recorded. 
• Record patient survival (if applicable, date and cause of death) 

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6.1.2 Year 1, Year 2, and Year 3 (End-of-Trial) 
The following visit windows applies: 
Year 1: 
(+/- 2 months) 
Year 2 and Year 3 (End-of-Trial): 
(+/- 4 months) 
The following activities and assessments will be performed: 
• Assessment of graft survival. For subjects with graft loss since last visit in the feeder 
trial or screening (if screening is done at a separate visit), date, reason for graft loss, 
medical history, and root cause will be recorded. 
• Record patient survival (if applicable, date and cause of death) 
• Collect information about graft rejection episodes, (classified by Banff 2017 or later). 
For-cause biopsies together with contemporaneous local DSA analyses, kidney 
function parameters (P-creatinine, U-albumin/creatinine ratio) and treatments (e.g. 
plasma exchange and IVIg) will be collected to assess the rejection episodes.  
• Record information from standard of care biopsies, if available 
• Sample for S/P-creatinine will be drawn (eGFR will be calculated by the Sponsor) 
• Collect urine sample for measurement of albumin/creatinine ratio  
• Sample for HLA antibodies, including DSA, and ADA will be drawn 
• Record comorbidity such as infections, malignancy, diabetes mellitus, cardiovascular 
events and comorbidity leading to worsening of kidney function, that occurred after 
end of trial in feeder trial  
• Record current immunosuppressive medications  
• Record treatment with dialysis  
• AEs related to trial procedure or IMP in feeder trial will be recorded, see section 9   
 
 

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7. TRIAL ASSESSMENTS  
7.1 Assessments related to Primary Endpoint 
The primary endpoint of this trial is to determine the overall graft survival, defined as time 
from start of treatment (imlifidase or plasma exchange) of active or chronic active AMR in 
feeder trial to graft loss, evaluated at year 3. Graft loss is defined as permanent return to 
dialysis for at least 6 weeks, re-transplantation, or nephrectomy. The date of graft loss will be 
recorded. If dialysis is used to define graft loss, the date of graft loss is the first day of the 
dialysis period defining the graft loss. 
7.2 Assessments related to Secondary Endpoints  
7.2.1 Overall graft survival at Years 1 and 2 
Graft survival at Year 3 is the primary endpoint but graft survival will be evaluated at Years 1 
and 2. 
7.2.2 Patient survival 
Overall patient survival is defined as time from start of treatment (imlifidase or plasma 
exchange) of active or chronic active AMR in the feeder trial to death for any cause, evaluated 
at Year 3. The date and cause of death will be recorded. 
7.2.3 Kidney function  
Evaluation of kidney function will be based on S/P-creatinine analysis and calculation of 
filtration rate (eGFR) using the MDRD GFR equation. Calculation of eGFR will be done 
directly in the eCRF. Albumin/creatinine ratio in urine will be collected.  
7.2.4 AMR rejection episodes and Graft rejection episodes (other than AMR episodes) 
Information about rejection episodes will be collected, according to Banff 2017 or later 
classification. For-cause biopsies together with contemporaneous local DSA analyses, kidney 
function parameters (creatinine, albumin/creatinine ratio in urine) and treatments (e.g. plasma 
exchange and IVIg) will be collected to assess the rejection episodes. 
7.2.5 Donor-specific antibody (DSA) levels  
Samples for determination of DSA will be analyzed in a single antigen bead assay (SAB-HLA). 
These assays allow determination of the mean fluorescence intensity (MFI) of antibodies in 
subject serum reacting to an array of individual HLA immobilized to beads. Analyses of DSA, 
will be performed centrally at Hansa Biopharma, Lund, Sweden, for samples taken at the visits. 
The date and actual time of collection of each sample will be recorded in the eCRF.  

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DSA analysed as standard of care and associated with a graft rejection episode will be recorded 
in the eCRF. DSAs for each patient will be identified by the respective site.    
7.2.6 Immunogenicity by Anti-Drug Antibodies (ADA) 
Samples for the determination of ADA levels in serum will be analysed for 
 
. The analysis will be performed at the central 
laboratory, 
 
. Full details of the analytical method used, and the analysis results will be described 
in a separate bioanalytical report. The ADA sample will be collected at all visits. The date and 
time of collection will be recorded on the laboratory requisition form and in the eCRF. 
7.2.7 Comorbidity 
Information about comorbidities that are medically relevant and registered in the subjects’ 
medical record will be collected. Medically relevant comorbidity are infections, malignancy, 
diabetes mellitus, cardiovascular events and comorbidities leading to worsening of kidney 
function. 
7.2.8 Demographics  
Information about gender, race and age (year) will be collected. 
8. BIOLOGICAL SAMPLING PROCEDURES 
8.1 Volume of Blood 
The total blood volume obtained will be about 60 mL over 3 years.   
8.2 Handling, Storage and Destruction of Biological Samples 
Samples analysed at the local laboratory will be disposed according to local practice. 
Biological blood samples collected for central analysis may be stored by the sponsor for a 
maximum of 5 years after completion of the trial report.  
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. 
8.3 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. 

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Hansa Biopharma keeps oversight of the entire life cycle through internal procedures, 
monitoring of trial sites and auditing of external laboratory providers. 
8.4 Withdrawal of Informed Consent for Biological Samples 
If a subject withdraws consent to the use of biological samples, the samples will be 
disposed/destroyed, if not already analysed and documented. 
The principal investigator: 
• Will ensure that subject withdrawal of informed consent is notified immediately to Hansa 
Biopharma. 
• Will ensure that biological samples from that subject, if stored at the trial site, are 
immediately identified, disposed/destructed and the action documented. 
• Will ensure the local 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 trial site. 
Hansa Biopharma ensures the central 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 trial 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. 
 
 

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9. ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
9.1 Definitions 
9.1.1 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 or trial procedure.  
No IMP will be administered in this trial and only AEs that the investigator judges as related 
to IMP administered in the feeder trial, and adverse events caused by a procedure in the 
protocol (such as blood sampling) will be captured and reported in this trial.   
9.1.2 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 
• 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. Examples of such events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
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. 

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9.2 Collection and Recording of Adverse Events 
In clinical trials, an AE/SAE can occur at any time after signing of the informed consent until 
the end of the trial.  
AEs will therefore be collected in the eCRF from the time of signing of the informed consent 
and throughout the trial.  
Adverse events caused by a procedure in the protocol (such as blood sampling) or judged as 
related to the IMP administered in the feeder trial are the only AEs that will be captured and 
reported in the trial.  
9.2.1 Variables 
The following variables will be recorded in the eCRF 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, version current at trial start, same 
version throughout the trial duration) whether the AE is serious or not, causality assessment, 
action taken (including actions taken with concomitant therapies), and outcome.  
9.2.1.1 Causality Assessment  
The investigator will make an assessment of the relationship for any AE caused by a 
procedure in the protocol (such as blood sampling) or judged as related to the IMP 
administered in the feeder trial using the following criteria: 
Related: a relationship to a trial procedure, or IMP administered in the feeder trial, cannot be 
excluded. Applicable to AEs where:  
• It follows a reasonable temporal sequence dosing with trial procedure or IMP 
administered in the feeder trial 
• It cannot be reasonably explained by the known characteristics of the subject’s clinical 
state, environmental or toxic factors, or other modes of therapy 
9.2.2 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. 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. 
9.2.3 Follow-up of Unresolved Adverse Events 
Any AEs that are unresolved at the subject’s last AE assessment in the trial 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 

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SAEs and AEs leading to discontinuation should be followed until the event resolves or 
stabilizes.  
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 trial, if judged necessary. 
9.2.4 Reporting of Serious Adverse Events 
SAEs will be recorded from the time of informed consent. Only SAEs caused by trial 
procedure or related to IMP in the feeder trial will be reported. SAEs will be reported on a 
separate SAE form.  
An assigned contract research organisation (CRO), 
 will be responsible for the 
SAEs handling in accordance with International Conference on Harmonisation (ICH) Good 
Clinical Practice (GCP) and local regulations. 
As soon as the investigator is aware of a potential SAE, he/she should contact 
 
and, in any case 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: 
  
e-mail: 
  
 
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up is undertaken immediately. Investigators or other site personnel must inform the 
 about 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. 
 will 
advise the investigator/trial site personnel how to proceed. 
The SAE reporting procedures are detailed in the trial specific Safety Management Plan. This 
plan is an agreement between Hansa Biopharma and 
. 
9.2.5 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 IMP caused the AE. 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.  

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 will be responsible for ensuring reporting all SUSARs to RAs in accordance 
with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) and 
local regulations. 
 is also responsible for informing all participating trial 
investigators of any SUSARs on an expedited basis and in accordance with applicable 
regulations. 
The SUSAR reporting procedures are detailed in the trial Safety Management Plan. This plan 
is an agreement between the Hansa Biopharma, and 
. In addition, Hansa 
Biopharma is responsible for informing all investigators in all other ongoing studies involving 
imlifidase about all SUSARs.  
Hansa Biopharma or the trial monitor will be responsible for ensuring reporting SUSARs to 
independent ethics committees (IEC) in EU.  
In US, it is the responsibility of the site investigator to promptly notify the Institutional 
Review Board (IRB) and other appropriate institutional regulatory bodies of all SUSARs 
received involving risk to human subjects as per their applicable requirements 
9.3 Pregnancy and Pregnancy Outcome 
Pregnancy is an exclusion criterion in the feeder trial and pregnancy tests are performed at the 
screening visit and end of trial visit. 
If a subject becomes pregnant during the trial, the subject will continue in the trial according 
to the trial protocol, if possible. A Pregnancy Report Form must be sent by the investigator to 
 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 trial. 
 will follow up on the 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-trial pregnancy and considered reasonably related to the trial 
drug by the investigator will be reported to Hansa Biopharma (or designee).  
 
 

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10. TRIAL MANAGEMENT 
10.1 Pre-Trial Activities 
All sites that are asked to participate in this trial must have participated in the feeder trial.  
Before the first subject is entered into the trial, a Hansa Biopharma representative will review 
and discuss the requirements of the clinical trial protocol and related documents with the 
investigational staff and also train them in any trial specific procedures and system(s) utilized 
at a site initiation visit (SIV). 
The principal investigator will ensure that appropriate training relevant to the trial is given to 
all staff, and that any new information relevant to the performance of this trial is forwarded to 
the staff involved. 
The principal investigator will maintain a record of all individuals involved in the trial 
(medical, nursing and other staff). 
10.2 Monitoring of the Trial 
During the trial, a Hansa Biopharma representative will have regular contacts with the trial 
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 eCRFs. 
• Perform Source Data Verification (SDV) (a comparison of the data in the eCRFs with the 
subject’s medical records at the hospital or practice, and other records relevant to the trial) 
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 monitor will be available between visits if the investigator(s) or 
other staff at the centre need information and advice about the trial conduct. Details about 
monitoring are specified in a trial specific monitoring plan. 
10.3 Source Data 
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.  

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The investigator will make all the trial-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 trial and 
to permit trial-related monitoring. 
10.4 Audit and Inspection 
The main purposes of an audit or inspection are to assess compliance with the trial 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 RAs 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/randomisation number will appear on these copies. 
The investigator should notify Hansa Biopharma without any delay of any inspection by a RA 
or IEC/IRB. 
10.5 Trial Agreements 
The principal investigator must comply with all the terms, conditions, and obligations of the 
clinical trial agreement for this trial. In the event of any inconsistency between this clinical 
trial protocol and the clinical trial agreement, the clinical trial protocol will prevail. 
Agreements between Hansa Biopharma and the principal investigator must be in place before 
any trial-related procedures can take place, or subjects be enrolled. 
 
 

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11. DATA MANAGEMENT 
11.1 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 trial database is declared clean and released to the statistician, a final copy of the 
database will be stored at Hansa Biopharma. 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. 
11.2 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.  
11.3 Coding 
For medical coding of AEs, comorbidity, and concomitant medication the most recent 
versions of the Medical Dictionary for Regulatory Activities (MedDRA) and WHO Drug 
Dictionary will be used at trial 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 trial closure/database lock. 
11.4 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. 
 
 

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12. STATISTICAL METHODS  
All analyses will be detailed in a separate Statistical Analysis Plan (SAP). 
12.1 Analysis Sets 
12.1.1 Full Analysis Set (FAS) 
The Full Analysis Set will be defined as all patients enrolled. Because of the observational 
nature of this trial no other analysis set will be defined and all data presentations and analyses 
will be based on the FAS. 
12.2 Subject Characteristics 
The data from the clinical assessments will be summarised or listed by treatment group and 
each 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.  
12.2.1 Subject Disposition 
All subjects screened will be accounted for. The number of subjects in the analysis sets and 
the number of subjects who complete the trial will be summarized by treatment group. 
Furthermore, the number of subjects who withdraw from the trial will be summarised overall 
and by treatment group and reason for withdrawal. Subjects screened but not found eligible 
will be listed with reason for screening failure.  
12.2.2 Demographics and Other Baseline Characteristics 
The subject’s demographics and other baseline characteristics will be summarised by 
treatment group. 
12.2.3 Recent and Concomitant Medication 
Recent and concomitant immunosuppression medication will be summarised by anatomical 
therapeutic chemical (ATC) code and generic drug name for each treatment group. 
12.3 Statistical Analysis of Primary Endpoints 
No formal statistical hypothesis testing will be performed in the trial. Data will be presented 
by treatment group. 

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12.3.1 Primary efficacy analysis 
Overall graft survival at Year 3. Graft survival is defined as time from start of treatment 
(imlifidase or plasma exchange) of active or chronic active AMR in feeder trial to graft loss, 
evaluated at year 3. 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 by treatment. 
The following events will be censored at the time of occurrence: withdrawal from the trial 
without graft loss, evaluation time point and end of trial without graft loss.  
The reason for graft loss will be tabulated by time. 
12.4 Statistical Analysis of Secondary Endpoints 
12.4.1 Graft survival at Year 1 and 2 
Graft survival at Year 1 and Year 2 will be evaluated as described under  12.3.1. 
12.4.2 Patient survival  
Patient survival, defined as time from start of treatment in feeder trial to death, evaluated at Year 
3 will be listed by patient and summarized by treatment.  
12.4.3 Kidney function  
Kidney function, as evaluated by eGFR, S/P-creatinine and albumin/creatinine ratio in urine at 
1, 2, and 3 years after start of treatment in feeder trial. Variables will be listed by patient and 
summarized by treatment at Year 1, 2, and 3 after start of treatment in feeder trial. Derivation 
of eGFR will be detailed in the SAP. 
12.4.4 Proportion of subjects with rejection episodes 
Proportion of subjects with presumed or biopsy-proven AMR episodes (classified according 
to Banff 2017 or later) and proportion of subjects with biopsy-proven rejection episodes, 
(other than AMR episodes) within 3 years after start of treatment in feeder trial will be listed 
and summarised by treatment group.  
12.4.5 DSA level at 1, 2, and 3 years after start of treatment in feeder trial  
DSA levels (measured using SAB-HLA assay) 1, 2 and 3 years after start of treatment in feeder 
trial will be summarized, listed, and presented graphically.  

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12.4.6 Immunogenicity 
Anti-imlifidase antibody 1, 2, and 3 years after start of treatment in feeder trial, will be listed 
and summarised.  
12.5 Analysis of Adverse Events 
Only adverse events related to trial procedure or related to IMP administered in feeder trial 
will be collected and listed. 
12.6 Determination of Sample Size 
As this is an observational follow up trial, no power calculations for sample size estimation 
were performed. All patients enrolled in the feeder trial (16-HMedIdeS-12) will be considered 
for inclusion in this trial. It is anticipated that approximately 30 patients, 20 from the imlifidase 
arm and 10 from the plasma exchange arm, may be included. 
13. CHANGES IN TRIAL CONDUCT OR PLANNED ANALYSES 
Any changes and deviations to plans described in the protocol and in the SAP must be 
documented. 
13.1 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 RAs, if applicable) 
have been obtained. 
Changes to the protocol to eliminate immediate hazard(s) to trial subjects may be 
implemented prior to IEC(s)/IRB(s) and RA approval. 
13.2 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. 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 trial and assess 
whether there is a need to update the protocol through an amendment to avoid future 
deviations.  
Planned protocol deviations are not permitted. 

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13.3 Statistical Analysis Plan 
Any changes to the SAP will be described in the Clinical Trial Report and/or in the Statistical 
Report. 
13.4 Premature Termination or Suspension of the Trial 
If the trial 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 trial 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 Trial, the investigator should promptly inform the Institution where applicable. 
In 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/favourable opinion of a trial, Hansa 
Biopharma should inform the investigators and institutions (where applicable) and provide 
them with a detailed written explanation of the termination or suspension. 
14. REPORTING AND PUBLICATION 
14.1 Clinical Trial Report 
The results from this trial will be reported in a clinical trial report (CTR) within one year after 
end-of-trial. This will be prepared by Hansa Biopharma and submitted for comments and 
signature to the coordinating (signatory) investigator(s). 
14.2 Confidentiality and Data Ownership 
Any confidential information relating to the IMP or the trial, including any data and results 
from the trial will be the exclusive property of Hansa Biopharma. The investigator and any 
other persons involved in the trial will protect the confidentiality of the proprietary 
information belonging to Hansa Biopharma. 
14.3 Publications  
14.3.1 Publication Policy 
At the end of the trial, 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 trial has no publication rights 
regarding the trial. 

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14.4 Public Disclosure 
The trial will be registered in a public clinical trials registry i.e. the U.S. National Institutes of 
Health register ClinicalTrials.gov. 
15. ETHICAL AND REGULATORY ASPECTS 
15.1 Ethical Conduct of the Trial 
This trial will be conducted in compliance with the approved protocol (including any 
approved amendments), the ICH E6 (R2) Good Clinical Practice (GCP), the ethical principles 
of the latest revision of the Declaration of Helsinki as adopted by the World Medical 
Association, applicable regulatory requirements, and local legislations. US sites will 
accordingly be under a US IND while European and other non-US sites will conduct the trial 
in compliance with respective country’s local legislation.  
The responsibilities of Hansa Biopharma, the monitor and the investigator are defined in the 
ICH GCP E6 (R2) consolidated guideline and applicable regulatory requirements in the 
country where the trial takes place. The investigator is responsible for adhering to the 
responsibilities of investigators defined in ICH GCP E6 (R2). For studies conducted in the 
USA, the investigator will additionally ensure adherence to the basic principles of GCP as 
outlined in the current version of 21 CFR, part 312, subpart D: “Responsibilities of Sponsors 
and Investigators”, part 50: “Protection of Human Subjects”, and part 56: “Institutional 
Review Boards.” 
15.2 Liabilities and Insurance 
Hansa Biopharma is, as the 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 trial subject for injury 
arising from the subject’s participation in the trial. 
15.3 Independent Ethics Committee(s) and Institutional Review Board(s)  
All ethical and regulatory approvals must be available before a subject is exposed to any trial-
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. 

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Hansa Biopharma will keep an updated list of submission and approval dates of all documents 
submitted to IEC(s). 
15.4 Regulatory Authority(ies) 
According to applicable regulatory requirements Hansa Biopharma will send required 
documents to the RAs. Hansa Biopharma will keep an updated list of submission and 
approval dates of all documents submitted to RAs. 
15.5 Subject Information and Informed Consent 
Before any trial-related activities and in agreement with applicable regulatory requirements, 
the investigator must give the subject oral and written information about the trial in a form 
that the subject can understand. The Investigator must ensure that the subject is fully informed 
about the aims, procedures, potential risks, any discomforts and expected benefits of the Trial. 
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 Trial at any time without prejudice. 
The original, signed Informed Consent Forms must be kept in the Investigator File.  
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 trial subject’s willingness to 
continue participation in the trial, a new Subject Information and Informed Consent Form will 
be forwarded to the IEC(s)/IRB(s) (and RAs, if required). The trial subjects will be informed 
about this new information and re-consent will be obtained. 
15.6 Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and 
Hansa Biopharma and 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 trial protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the trial, or the data will be released to any 
unauthorized third party. 
The trial 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) and pharmacy records for the subjects 
in this trial. The clinical trial site will permit access to such records. 

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16. ARCHIVING 
16.1 Retention of Clinical Trial Site Documentation 
The investigator is responsible for maintaining all the records, which enable the conduct of 
the trial at the site to be fully understood, in compliance with ICH-GCP. The trial 
documentation including all the relevant correspondence should be kept by the investigator 
for at least 25 years after the completion or discontinuation of the trial 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 eCRF 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 trial. 
No trial site document may be destroyed without prior written agreement between the 
investigator and Hansa Biopharma. Should the investigator elect to assign the trial 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. 
16.2 Trial Master File 
Hansa Biopharma will archive the Trial Master File in accordance with ICH-GCP and 
applicable regulatory requirements. 
 
 

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17. REFERENCES 
Gloor J, Cosio F, Lager DJ, Stegall MD. The spectrum of antibody-mediated renal allograft 
injury: implications for treatment. Am J Transplant. 2008;8:1367-73. 
Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, et al. 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. 2018;18:293-307. 
Jordan SC, Reinsmoen N, Peng A, Lai CH, Cao K, Villicana R, et al. Advances in diagnosing 
and managing antibody-mediated rejection. Pediatr Nephrol. 2010;25:2035-45. 
Lefaucheur C, Loupy A, Hill GS, Andrade J, Nochy D, Antoine C, et al. Preexisting donor-
specific HLA antibodies predict outcome in kidney transplantation. J Am Soc 
Nephrol. 2010;21:1398-406. 
OPTN. Organ Procurement and Transplantation Network. Scientific Registry of Transplant 
Recipients. 2012 Annual Data Report. (OPTN). optn.transplant.hrsa.gov/ 2012. 
Port FK, Wolfe RA, Mauger EA, Berling DP, Jiang K. Comparison of survival probabilities 
for dialysis patients vs cadaveric renal transplant recipients. JAMA. 1993;270:1339-
43. 
Reinsmoen NL, Lai CH, Vo A, Cao K, Ong G, Naim M, et al. Acceptable donor-specific 
antibody levels allowing for successful deceased and living donor kidney 
transplantation after desensitization therapy. Transplantation. 2008;86:820-5. 
Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, et al. Recommended 
Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 
Expert Consensus From the Transplantion Society Working Group. Transplantation. 
2020;104:911-22. 
Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the 
causes of kidney transplant failure: the dominant role of antibody-mediated rejection 
and nonadherence. Am J Transplant. 2012;12:388-99. 
 
 

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18. APPENDIX 1 
18.1 Protocol Amendment 01 
Protocol Amendment Number 01 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 overall rationale for the changes implemented in the protocol is the change of the CRO 
responsible for SAE/SUSAR reporting. In addition, a few editorial updates have been made. 
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. 
OTHER DOCUMENTS AND SYSTEM IMPACTED BY THE AMENDMENT 
All study documents related to SAE/SUSAR reporting will be updated as required. 
 
1 
Change in CRO responsible for SAE/SUSAR reporting 
Hansa Biopharma has changed the CRO responsible for SAE/SUSAR reporting and the 
protocol has been updated with the new contact details. 
1.1 
Section 9.2.4 Reporting of Serious Adverse Events (2nd paragraph to 5th 
 
paragraph)  
Changed from:  
An assigned contract research organisation (CRO), 
 will be responsible 
for the SAEs handling in accordance with International Conference on Harmonisation (ICH) 
Good Clinical Practice (GCP) and local regulations. 
As soon as the investigator is aware of a potential SAE, he/she should contact 
 
and, in any case 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: 
 
e-mail: 
  
 
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up is undertaken immediately. Investigators or other site personnel must inform the 

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 about 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 
 will advise the investigator/trial site personnel how to proceed. 
The SAE reporting procedures are detailed in the trial specific Safety Management Plan. This 
plan is an agreement between Hansa Biopharma and 
. 
Changed to:  
An assigned contract research organisation (CRO), 
 will 
be responsible for the SAEs handling in accordance with International Conference on 
Harmonisation (ICH) Good Clinical Practice (GCP) and local regulations. 
As soon as the investigator is aware of a potential SAE, he/she should contact 
 
and, in any case 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: 
 
e-mail: 
 
 
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up is undertaken immediately. Investigators or other site personnel must inform the 
 about 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. 
 will advise the investigator/trial site 
personnel how to proceed. 
The SAE reporting procedures are detailed in the trial specific Safety Management Plan. This 
plan is an agreement between Hansa Biopharma and 
. 
1.2 
Section 9.2.5 Reporting of Suspected Unexpected Serious Adverse Reactions 
 
(3rd and 4th paragraph) 
Changed from:  
 will be responsible for ensuring reporting all SUSARs to RAs in 
accordance with International Conference on Harmonisation (ICH) Good Clinical Practice 
(GCP) and local regulations. 
 is also responsible for informing all 
participating trial investigators of any SUSARs on an expedited basis and in accordance with 
applicable regulations. 
The SUSAR reporting procedures are detailed in the trial Safety Management Plan. This plan 
is an agreement between the Hansa Biopharma, and 
. In addition, 
Hansa Biopharma is responsible for informing all investigators in all other ongoing studies 
involving imlifidase about all SUSARs.  

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Changed to:  
 will be responsible for ensuring reporting all SUSARs 
to RAs in accordance with International Conference on Harmonisation (ICH) Good Clinical 
Practice (GCP) and local regulations.
 is also 
responsible for informing all participating trial investigators of any SUSARs on an expedited 
basis and in accordance with applicable regulations. 
The SUSAR reporting procedures are detailed in the trial Safety Management Plan. This plan 
is an agreement between the Hansa Biopharma, and 
. In 
addition, Hansa Biopharma is responsible for informing all investigators in all other ongoing 
studies involving imlifidase about all SUSARs.  
1.3 
Section 9.3 Pregnancy and Pregnancy Outcome (2nd paragraph) 
Changed from:  
…. A Pregnancy Report Form must be sent by the investigator to 
 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 trial. 
 will follow up … 
Changed to:  
… A Pregnancy Report Form must be sent by the investigator to
 
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 trial. 
 will 
follow up ... 
 
2 
Editorial changes 
A few minor editorial changes were made without any implications on the study protocol and 
procedures. 
2.1 
Title page 
Changed from:  
Clinical Trial 1.0 
Protocol version and date: 
1.0, 02 OCT-2020 
Revision history: 
N/A 
Changed to:  
Clinical Trial 1.0Protocol 

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Protocol version and date: 
1.01, 02 OCT 202022-NOV-2021 
Revision history: 
N/A 
 
2.2 
Signature page (Sponsor’s signature) 
Changed from:  
This clinical trial protocol, identified by the version and date above, is approved by: 
Chief Operating Officer / Chief Scientific Officer 
 
 
 
 
Signature 
 
Date 
Vice President R&D / Senior Medical Director, Hansa Biopharma AB 
 
 
 
 
Signature 
 
Date 
Signatory Coordinating Principal Investigator 
 
 
 
 
 
 
Signature 
 
Date 
Changed to:  
This protocol version includes Non-Substantial Amendment No.01. According to Hansa 
Biopharma’s SOP, only the responsible CRM approves this type of amendments by signing 
the “Hansa Biopharma AB Approval of Non-Substantial Amendment to Protocol “-form.  
It is referred to the previous protocol (version 1.0, 02-OCT-2020) for approvals by Hansa 
Biopharma’s signatories and the signatory coordinating principal investigator. 
This clinical trial protocol, identified by the version and date above, is approved by: 
Chief Operating Officer / Chief Scientific Officer 
 
 
 
 
Signature 
 
Date 
Vice President R&D / Senior Medical Director, Hansa Biopharma AB 
 
 
 
 
Signature 
 
Date 
Signatory Coordinating Principal Investigator 
 
 
 
 
 
 

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Signature 
 
Date 
 
2.3 
Investigators and Clinical Administration Structure (2nd row in table) 
Changed from:  
Sponsor’s Medical 
Expert 
Name and 
title: 
Address: 
 
 
Phone: 
E-mail: 
 
 
 
 
 
 
 
Changed to: 
Sponsor’s Medical 
ExpertSenior Medical 
Director 
Name and 
title: 
Address: 
 
 
Phone: 
E-mail: 
 
 
 
 
 
 
 
 
 
2.4 
New Section – Protocol Revision History Summary of Changes 
Changed from:  
- 
Changed to: 
Protocol Revision History including Summary of Changes 
Protocol 
Version 
Date 
Including 
Amendment 
Type and No. 
Overall Rationale for Changes 
1.1 
22-NOV-2021 
Non-
substantial 
amendment 
No. 01 
• 
Change in CRO responsible for 
SAE/SUSAR reporting 
• 
Updated number of participating sites to 
approximately 14 
1.0 
02-OCT-2020 
N/A 
Initially approved protocol 
 
See Appendix 1 “Clinical Study Protocol Amendment” for details of Amendment No. 01. 

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2.5 
Section 1.1 Background (Table 1, 1st row) 
Changed from: 
Trial No / 
EudraCT No 
Phase / 
Subjects 
Main objectives 
 
Changed to: 
Trial No. / 
EudraCT No./ 
IND No. 
Phase / 
Subjects 
Main objectives 
 
2.6 
Section 3.3 Planned Number of Trial Sites and Subjects 
Changed from: 
All sites included in the feeder trial, approximately 8-11 sites, in US,….. 
Changed to: 
All sites included in the feeder trial, approximately 8 1114 sites, in US,….. 
2.7 
Section 6.1.1 Screening (Header and 1st paragraph) 
Changed from:  
6.1.1 
Screening (may be conducted at the earliest at the last visit in feeder trial and at 
the latest at Year 1 (one year after start of treatment in feeder trial +/- the visit window of 2 
months)  
Changed to:  
6.1.1 
Screening (may be conducted at the earliest at the last visit in feeder trial and at 
the latest at Year 1 (one year after start of treatment in feeder trial +/  the visit window of 2 
months)  
Screening may be conducted at the earliest at the last visit in feeder trial and at the latest at 
Year 1 (one year after start of treatment in feeder trial +/- the visit window of 2 months). 
The following assessments and activities will be performed:  
2.8 
Section 6.1.2 Year 1, Year 2, and Year 3 (End-of-Trial) (Header and 1st 
 
paragraph) 
Changed from:  
6.1.2 
The following activities and assessments will be performed at Year 1(+/-2 
months), Year 2 (+/-4 months), Year 3 ((+/-4 months)and End-of-Trial) 
Changed to:  
6.1.1 
The following activities and assessments will be performed at Year 1(+/ 2 
months), Year 2 (+/-4 months), Year 3 ((+/ 4 months)and End of Trial)Year 1, Year 2, and 
Year 3 (End-of-Trial) 
The following visit windows applies: