Clinical trial NCT05232864
Conditions: Lupus Nephritis
Keywords: Lupus Nephritis secukinumab (AIN457) estimated glomerular filtration rate Urine Protein-to-Creatinine Ratio Standard of Care background therapy
Sponsor: Novartis Pharmaceuticals
Start date: 2022-08-22; Completion date: 2023-08-23
Enrollment: 31 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this open-label extension study was to provide treatment with secukinumab for subjects who completed core study treatment in Study CAIN457Q12301 (NCT04181762), and to obtain further data on long-term efficacy, safety and tolerability of secukinunab in patients with active lupus nephritis (LN).

Detailed description:
Investigators used their clinical judgement to decide if it might be beneficial, in terms of overall improvement and response to therapy, for subjects to enter the extension study. The planned total combined duration for the core study and this extension study was five years.

At Week 104 of the core study CAIN457Q12301, eligible subjects who completed the assessments associated with the core study visit subsequently continued in the extension study on the dose of secukinumab 300 mg administered every four weeks.

A total of 31 subjects were enrolled and received secukinumab 300 mg every four weeks until study termination. Recruitment in this study was stopped on 26-May-2023.

This study along with the core study (CAIN457Q12301) were terminated early by Novartis due to futile results of interim analysis 1 of the core study. There were no safety related reasons for early termination of either of the studies.

Arms: arm 1: Secukinumab 300 mg solution for subcutaneous (s.c.) injection in a 2mL Pre-Filled Syringe (PFS)
Interventions: intervention 1: Secukinumab
Intervention descriptions: intervention 1: 300 mg solution for subcutaneous (s.c.) injection in a 2mL Pre-Filled Syringe (PFS)

Protocol documents:
Prot_000.pdf: 
Official Title:    A Three-year, Open-label Extension Study of Subcutaneous
Secukinumab to Evaluate the Long-term Efficacy, 
Safety and Tolerability in Patients With Active Lupus Nephritis
NCT Number: 
NCT05232864 
Document Date: 
Original Protocol: 10-December-2021


Novartis Research and Development 
Secukinumab (AIN457) 
Clinical Trial Protocol CAIN457Q12301E1
 A three-year, open-label extension study of subcutaneous 
secukinumab to evaluate the long-term efficacy, safety and 
tolerability in patients with active lupus nephritis 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
2021-005772-19 
Version number: 
00 (Original Protocol) 
Clinical Trial Phase: 
III 
Release date: 
10-Dec-2021 (content final)
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 4.0 dated 15-Feb-2021 


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Protocol No. CAIN457Q12301E1 
 
Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 5 
List of abbreviations ............................................................................................................ 6 
Glossary of terms ................................................................................................................. 9 
Protocol summary .............................................................................................................. 11 
1 
Introduction ....................................................................................................................... 13 
1.1 
Background ............................................................................................................ 13 
1.2 
Purpose .................................................................................................................. 15 
2 
Objectives, endpoints and estimands ................................................................................. 15 
2.1 
Primary estimands ................................................................................................. 16 
2.2 
Secondary estimands ............................................................................................. 17 
3 
Study design ...................................................................................................................... 17 
4 
Rationale ............................................................................................................................ 18 
4.1 
Rationale for study design ..................................................................................... 18 
4.1.1 
Rationale for choice of background therapy ......................................... 18 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 18 
4.3 
Rationale for choice of control drugs (comparator/placebo) or combination 
drugs ...................................................................................................................... 18 
4.4 
Purpose and timing of interim analyses/design adaptations .................................. 18 
4.5 
Risks and benefits .................................................................................................. 19 
4.6 
Rationale for Public Health Emergency mitigation procedures ............................ 19 
5 
Study Population ............................................................................................................... 19 
5.1 
Inclusion criteria .................................................................................................... 20 
5.2 
Exclusion criteria ................................................................................................... 20 
6 
Treatment ........................................................................................................................... 21 
6.1 
Study treatment ...................................................................................................... 21 
6.1.1 
Investigational and control drugs .......................................................... 21 
6.1.2 
Additional study treatments .................................................................. 22 
6.1.3 
SoC background therapy ....................................................................... 22 
6.1.4 
Treatment arms/group ........................................................................... 22 
6.1.5 
Treatment duration ................................................................................ 22 
6.2 
Other treatment(s) .................................................................................................. 23 
6.2.1 
Concomitant therapy ............................................................................. 23 
6.2.2 
Prohibited medication ........................................................................... 24 
6.2.3 
Rescue medication ................................................................................ 24 


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6.3 
Preparation and dispensation ................................................................................. 25 
6.3.1 
Handling of study treatment and other treatment .................................. 25 
6.4 
Participant numbering, treatment assignment, randomization .............................. 26 
6.4.1 
Participant numbering ........................................................................... 26 
6.4.2 
Treatment assignment, randomization .................................................. 27 
6.5 
Treatment blinding ................................................................................................ 27 
6.6 
Dose escalation and dose modification.................................................................. 27 
6.6.1 
Definitions of dose limiting toxicities (DLTs) ...................................... 27 
6.6.2 
Dose modifications ................................................................................ 27 
6.6.3 
Follow-up for toxicities ......................................................................... 27 
6.7 
Additional treatment guidance ............................................................................... 28 
6.7.1 
Treatment compliance ........................................................................... 28 
6.7.2 
Recommended treatment of adverse events .......................................... 28 
6.7.3 
Emergency breaking of assigned treatment code .................................. 29 
7 
Informed consent procedures ............................................................................................ 29 
8 
Visit schedule and assessments ......................................................................................... 30 
8.1 
Enrollment ............................................................................................................. 35 
8.2 
Screening ............................................................................................................... 35 
8.2.1 
Information to be collected on screening failures ................................. 35 
8.3 
Participant demographics/other Baseline characteristics ....................................... 35 
8.4 
Efficacy .................................................................................................................. 35 
8.4.1 
Complete Renal Response (CRR) ......................................................... 35 
 
 35 
8.4.3 
Estimated Glomerular Filtration Rate (eGFR) ...................................... 36 
8.4.4 
Urine Protein-to-Creatinine Ratio (UPCR) ........................................... 36 
 
 36 
8.4.6 
Appropriateness of efficacy assessments .............................................. 36 
8.5 
Safety ..................................................................................................................... 37 
8.5.1 
Laboratory evaluations .......................................................................... 38 
8.5.2 
Electrocardiogram (ECG) ..................................................................... 39 
8.5.3 
Pregnancy and assessments of fertility ................................................. 40 
8.5.4 
Appropriateness of safety measurements .............................................. 41 
8.6 
Additional assessments .......................................................................................... 41 
9 
Discontinuation and completion ........................................................................................ 41 
9.1 
Discontinuation from study treatment and from study .......................................... 41 
9.1.1 
Discontinuation from study treatment ................................................... 41 


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9.1.2 
Discontinuation from study ................................................................... 42 
9.1.3 
Lost to follow-up ................................................................................... 42 
9.2 
Withdrawal of informed consent/Opposition to use data/biological samples ....... 42 
9.3 
Study completion and post-study treatment .......................................................... 43 
9.4 
Early study termination by the sponsor ................................................................. 44 
10 Safety monitoring, reporting and committees ................................................................... 44 
10.1 
Definition of adverse events and reporting requirements ...................................... 44 
10.1.1 
Adverse events ...................................................................................... 44 
10.1.2 
Serious adverse events .......................................................................... 45 
10.1.3 
SAE reporting........................................................................................ 46 
10.1.4 
Pregnancy reporting .............................................................................. 47 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 47 
10.2 
Additional Safety Monitoring ................................................................................ 48 
10.2.1 
Liver safety monitoring ......................................................................... 48 
10.3 
Committees ............................................................................................................ 49 
10.3.1 
Data Monitoring Committee ................................................................. 49 
10.3.2 
Steering Committee ............................................................................... 49 
11 Data Collection and Database management ...................................................................... 49 
11.1 
Data collection ....................................................................................................... 49 
11.2 
Database management and quality control ............................................................ 50 
11.3 
Site monitoring ...................................................................................................... 50 
12 Data analysis and statistical methods ................................................................................ 51 
12.1 
Analysis sets .......................................................................................................... 51 
12.2 
Participant demographics and other Baseline characteristics ................................ 51 
12.3 
Treatments ............................................................................................................. 51 
12.4 
Analysis supporting primary objectives ................................................................ 51 
12.4.1 
Definition of primary endpoint(s) ......................................................... 51 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 52 
12.4.3 
Handling of intercurrent events of primary estimand ........................... 52 
12.4.4 
Handling of missing values not related to intercurrent event ............... 52 
12.4.5 
Sensitivity analyses ............................................................................... 52 
12.4.6 
Supplementary analysis ......................................................................... 52 
12.5 
Analysis supporting secondary objectives ............................................................. 52 
 
 52 
 
 52 
12.7 
Interim analyses ..................................................................................................... 53 


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12.8 
Sample size calculation.......................................................................................... 53 
12.8.1 
Primary endpoint(s) ............................................................................... 53 
13 Ethical considerations and administrative procedures ...................................................... 53 
13.1 
Regulatory and ethical compliance ........................................................................ 53 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 54 
13.3 
Publication of study protocol and results............................................................... 54 
13.4 
Quality Control and Quality Assurance ................................................................. 54 
13.5 
Participant Engagement ......................................................................................... 54 
14 Protocol adherence ............................................................................................................ 55 
14.1 
Protocol amendments............................................................................................. 55 
15 References ......................................................................................................................... 56 
16 Appendices ........................................................................................................................ 59 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs ......................... 59 
16.2 
Appendix 2: Liver event and laboratory trigger definitions & follow-up 
requirements .......................................................................................................... 59 
16.3 
Appendix 3: Estimation of eGFR by the CKD-EPI .............................................. 61 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 15 
Table 6-1 
Investigational drug and Control drug .................................................. 21 
Table 6-2 
Background therapy .............................................................................. 22 
Table 8-1 
Assessment Schedule ............................................................................ 31 
Table 8-2 
Assessments specifications ................................................................... 37 
Table 8-3 
Test categories and names ..................................................................... 38 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 48 
Table 16-1 
Safety Analyses: Expanded limits and Notable Criteria ....................... 59 
Table 16-2 
Liver event and laboratory trigger definitions ...................................... 59 
Table 16-3 
Follow up requirements for liver laboratory triggers ............................ 60 
List of figures 
Figure 3-1 
Study Design ......................................................................................... 17 
Figure 8-1 
Timing of study procedures .................................................................. 40 
 


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List of abbreviations 
ACE 
Angiotensin-converting enzyme 
ACR 
American College of Rheumatology 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
aPTT 
activated Partial Thromboplastin Time  
ARBs 
Angiotensin receptor blocker(s) 
AST 
Aspartate Aminotransferase 
axSpA 
Axial spondyloarthritis 
BAFF 
B-cell activating factor  
BMI 
Body Mass Index 
CFR 
Code of Federal Regulation 
CHMP 
Committee for Medicinal Products for Human Use 
CKD 
Chronic Kidney Disease 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CMO&PS 
Novartis Chief Medical Office and Patient Safety 
CNIs 
Calcineurin inhibitors 
CO 
Country Organization 
CRA 
Clinical Research Associate 
CRF 
Case Report/Record Form (paper or electronic) 
CRO  
Clinical Research Organization 
CRR 
Complete Renal Response 
CS 
Corticosteroid(s) 
CSR 
Clinical study report 
CYC 
Cyclophosphamide 
DBP 
Diastolic Blood Pressure 
DLT 
Dose Limiting Toxicity 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
dsDNA 
double stranded DNA 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
eGFR 
estimated Glomerular Filtration Rate  
EMA 
European Medicines Agency 
EOS 
End of Study 
EOT 
End of Treatment 
ERA-
EDTA 
European Renal Association – European Dialysis and Transplant Association 
eSAE 
Electronic Serious Adverse Event 
eSource 
Electronic Source 
ESRD 
End Stage Renal Disease 
EU 
European Union 
EULAR 
European League Against Rheumatism 
F/U 
Follow up 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 


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FMV 
First Morning Void 
GCP 
Good Clinical Practice 
GCS 
Global Clinical Supply 
GGT 
Gamma-glutamyl transferase 
h 
Hour 
HbA1c 
Hemoglobin A1c 
HDL 
High Density Lipoprotein 
i.v. 
intravenous 
IB 
Investigator's Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use 
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
IgG1 
Immunoglobulin G1 
IL-17 
Interleukin 17 
IMP 
Investigational Medicinal Product 
IN 
Investigator Notification 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ISN 
International Society of Neurology 
IUD 
Intrauterine device  
IUS 
Intrauterine system 
kg 
Kilogram 
LDL 
Low Density Lipoprotein 
LFT 
Liver function test  
LLN 
lower limit of normal 
LN 
Lupus Nephritis 
MCV 
Mean corpuscular volume 
MedDRA 
Medical dictionary for regulatory activities  
mg 
milligram(s) 
mL 
milliliter(s) 
MMF 
Mycophenolate Mofetil  
MPA 
Mycophenolic Acid  
MRA 
Magnetic resonance angiography 
MUGA 
Multiple gated acquisition 
NSAIDs 
Nonsteroidal Anti-Inflammatory Drug(s) 
OHP 
Off-site Healthcare Professional 
p.o. 
oral(ly) 
PFS 
Prefilled syringe 
PRR 
Partial Renal Response 
PsA 
Psoriatic arthritis 
PsO 
Psoriasis 
PSW 
Premature Participant/Subject Withdrawal 
PT 
prothrombin time 
PY 
Patient Year 


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QMS  
Quality Management System 
QTcF 
QT interval corrected by Fridericia’s formula 
R Value 
ALT/ALP x ULN 
RBC 
Red Blood Cell(s) 
RPS 
Renal Pathology Society 
s.c. 
subcutaneous 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
SD 
standard deviation 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvic Transaminase 
SLE 
Systemic Lupus Erythematosus  
SoC 
Standard of Care 
SOP 
standard operating procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TBL 
Total bilirubin 
TD 
Treatment Discontinuation 
TEAE 
Treatment-emergent adverse event 
TH17 
T helper type 17  
 
 
ULN 
upper limit of normal 
UPCR 
Urine Protein-to-Creatinine Ratio 
WBC 
White Blood Cell(s) 
WHO 
World Health Organization  
WoC 
Withdrawal of Consent 
β-hCG  
β-subunit of human chorionic gonadotropin 


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Glossary of terms 
Additional treatment 
Medicinal products that may be used during the clinical trial as described in the 
protocol, but not as an investigational medicinal product (e.g. any background 
therapy) 
Assessment 
A procedure used to generate data required by the study 
Biologic Samples 
A biological specimen including, for example, blood (plasma, serum), saliva, 
tissue, urine, stool, etc. taken from a study participant  
Clinical Trial Team 
A group of people responsible for the planning, execution and reporting of all 
clinical trial activities. Examples of team members include the Study Lead, 
Medical Monitor, Trial Statistician etc. 
Coded Data 
Personal Data which has been de-identified by the investigative center team by 
replacing personal identifiers with a code. 
Cohort 
A group of individuals who share a common exposure, experience or 
characteristic, or a group of individuals followed-up or traced over time 
Control drug 
A study drug (active or placebo) used as a comparator to reduce assessment 
bias, preserve blinding of investigational drug, assess internal study validity, 
and/or evaluate comparative effects of the investigational drug 
Cycles 
Number and timing or recommended repetitions of therapy are usually expressed 
as number of days (e.g., q28 days) 
Discontinuation from study 
Point/time when the participant permanently stops receiving the study treatment 
and further protocol required assessments or follow-up, for any reason. No 
specific request is made to stop the use of their samples or data. 
Discontinuation from study 
treatment 
Point/time when the participant permanently stops receiving the study treatment 
for any reason (prior to the planned completion of study drug administration, if 
any). Participant agrees to the other protocol required assessments including 
follow-up. No specific request is made to stop the use of their samples or data. 
Dosage 
Dose of the study treatment given to the participant in a time unit (e.g. 100 mg 
once a day, 75 mg twice a day) 
Electronic Data Capture 
(EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study data 
using data collection systems, such as Web-based applications, interactive voice 
response systems and clinical laboratory interfaces. EDC includes the use of 
Electronic Case Report Forms (eCRFs) which are used to capture data 
transcribed from source data/documents used at the point of care 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last participant 
Enrollment 
Point/time of participant entry into the study at which informed consent must be 
obtained. The action of enrolling one or more participants 
Estimand  
As defined in the ICH E9(R1) addendum, estimand is a precise description of the 
treatment effect reflecting the clinical question posed by the trial objective. It 
summarizes at a population-level what the outcomes would be in the same 
participants under different treatment conditions being compared. Attributes of an 
estimand include the population, variable (or endpoint) and treatment of interest, 
as well as the specification of how the remaining intercurrent events are 
addressed and a population-level summary for the variable. 
Intercurrent events 
Events occurring after treatment initiation that affect either the interpretation or 
the existence of the measurements associated with the clinical question of 
interest. 
Investigational drug/ 
treatment 
The drug whose properties are being tested in the study 
Medication number 
A unique identifier on the label of medication kits 
Off-site 
Describes trial activities that are performed at remote location by an off-site 
healthcare professional, such as procedures performed at the participant's home. 
Off-site healthcare 
Professional (OHP) 
A qualified healthcare professional, such as include those used in the study e.g. 
Nurse, Phlebotomist, Physician, who performs certain protocol procedures for the 
participant in an off-site location such as a participant's home. 


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Other treatment 
Treatment that may be needed/allowed during the conduct of the study (i.e., 
concomitant or rescue therapy) 
Participant 
A trial participant (can be a healthy volunteer or a patient). "Participant" 
terminology is used in the protocol whereas term "Subject" is used in data 
collection 
Participant number 
A unique number assigned to each participant upon signing the informed 
consent. This number is the definitive, unique identifier for the participant and 
should be used to identify the participant throughout the study for all data 
collected, sample labels, etc. 
Period 
The subdivisions of the trial design (e.g., Screening, Treatment, Follow-up) which 
are described in the Protocol. Periods define the study phases and will be used in 
clinical trial database setup and eventually in analysis 
Personal data 
Participant information collected by the Investigator that is coded and transferred 
to Novartis for the purpose of the clinical trial. This data includes participant 
identifier information, study information and biological samples. 
Randomization 
The process of assigning trial participants to investigational drug or 
control/comparator drug using an element of chance to determine the 
assignments in order to reduce bias. 
Randomization number 
A unique identifier assigned to each randomized participant 
Remote 
Describes any trial activities performed at a location that is not the investigative 
site where the investigator will conduct the trial, but is for example a home or 
another appropriate location 
Screen Failure 
A participant who did not meet one or more criteria that were required for 
participation in the study 
Source Data/Document 
Source data refers to the initial record, document, or primary location from where 
data comes. The data source can be a database, a dataset, a spreadsheet or 
even hard-coded data, such as paper or eSource 
Start of the clinical trial 
The start of the clinical trial is defined as the signature of the informed consent by 
the first participant 
Study treatment 
Any drug or combination of drugs or intervention administered to the study 
participants as part of the required study procedures; includes investigational 
drug(s), control(s) or background therapy 
Treatment arm/group  
A treatment arm/group defines the dose and regimen or the combination and may 
consist of 1 or more cohorts. 
Variable (or endpoint) 
The variable (or endpoint) to be obtained for each participant that is required to 
address the clinical question. The specification of the variable might include 
whether the participant experiences an intercurrent event. 
Withdrawal of study 
consent (WoC) / 
Opposition to use of data 
/biological samples 
Withdrawal of consent from the study occurs when the participant explicitly 
requests to stop use of their data and biological samples (opposition to use data 
and biological samples) AND no longer wishes to receive study treatment AND 
does not agree to further protocol required assessments. This request should be 
in writing (depending on local regulations) and recorded in the source 
documentation. 
Opposition to use data/biological samples occurs in the countries where 
collection and processing of personal data is justified by a different legal reason 
than consent. 


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Protocol summary 
Protocol 
number 
CAIN457Q12301E1 
Full Title 
A three-year, open-label extension study of subcutaneous secukinumab to evaluate the 
long-term efficacy, safety and tolerability in patients with active lupus nephritis 
Brief title 
Open-label extension study of efficacy, safety and tolerability of secukinumab in patients 
with active lupus nephritis 
Sponsor and 
Clinical Phase 
Novartis, Phase III 
Investigation 
type 
Biological 
Study type 
Interventional 
Purpose 
The purpose is to provide treatment with secukinumab delivered subcutaneously (s.c.) via 
pre-filled syringe (PFS) for participants who complete study treatment until the Week 104 of 
the core study and to obtain long term efficacy, safety and tolerability data 
Primary 
Objective(s)  
The primary objective is to assess long-term efficacy of secukinumab with respect to 
Complete Renal Response (CRR) over time up to Week 260 in adult participants with 
Lupus Nephritis (ISN/RPS Class III or IV, with or without co-existing class V features) on 
background SoC therapy 
 
 
 
Study design 
A multicenter, open-label, extension study of s.c. secukinumab to evaluate long-term 
efficacy, safety and tolerability up to three years in patients with Lupus Nephritis 
Rationale 
This three-year open-label extension study will offer continuous secukinumab therapy to 
eligible participants from the core study CAIN457Q12301 and will provide long-term 
efficacy and safety data. The proposal to continue treatment with subcutaneous (s.c.) 
doses of 300 mg administered every four weeks, is based on the need for long-term 
treatment exposure in participants suffering from a chronic illness such as LN with 
relapsing and remitting course. 
The regular assessments of disease activity would ensure that participants who are 
experiencing worsening of disease can exit the study upon their own decision or based on 
the advice of the investigator at any time. 
Study 
population 
The study population will consist of male and female participants aged from 18 to 75 years 
(at time of Core Study Screening) who were diagnosed with active LN-World Health 
Organization (WHO) or International Society of Nephrology/Renal Pathology Society 
(ISN/RPS) Class III or IV [excluding III (C), IV-S (C) and IV-G (C)], with or without co-
existing class V features at SCREENING in the core study CAIN457Q12301, and who have 
completed the entire treatment period up to and including Week 104 of the core study. 
Key Inclusion 
criteria 
● Participant must have both participated in core study and completed the entire treatment 
period up to and including Week 104 of the core study CAIN457Q12301. 
● Participant must be deemed by the investigator to benefit from secukinumab therapy. 
● Signed informed consent must be obtained prior to participation in the study 
Key Exclusion 
criteria 
● Any participant taking other concomitant biologic immunomodulating agent(s) except 
secukinumab. 
● Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a 
female after conception and until the termination of gestation, confirmed by a positive 
human chorionic gonadotropin (hCG)laboratory test. 
● Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using highly effective methods of contraception during 
the entire study or longer if required by locally approved prescribing information (e.g., in 
European Union (EU) 20 Weeks). Highly effective methods of contraception are 
recommended due to the known teratogenic effect of SoC (MPA) 
Study 
treatment 
Secukinumab 300 mg solution for s.c. injection in a 2mL Pre-Filled Syringe (PFS)  


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Treatment of 
interest 
Secukinumab 300 mg every 4 weeks along with Standard of Care (MPA and low dose 
corticosteroids) 
Efficacy 
assessments 
CRR is a composite endpoint based on: 
● estimated Glomerular Filtration Rate (eGFR) 
● Urine Protein-to-Creatinine Ratio (UPCR) 
Key safety 
assessments 
Adverse events/Serious adverse events 
Laboratory evaluations 
Physical Examination 
Vital Signs 
Weight 
Pregnancy test 
Tolerability of secukinumab 
Data analysis 
All data will be summarized descriptively for all participants by core study treatment groups 
in Full Analysis Set. Summary statistics for continuous variables will generally include the 
number of subjects (N), mean, standard deviation (SD), median, minimum and maximum. 
For categorical or binary variables, the frequency and percent of subjects in each category 
will be presented. All details of statistical analyses will be specified in Statistical Analysis 
Plan (SAP). 
Key words 
Lupus Nephritis, secukinumab (AIN457), estimated glomerular filtration rate (eGFR), Urine 
Protein-to-Creatinine Ratio (UPCR), Standard of care (SoC) background therapy 


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1 
Introduction 
1.1 
Background 
Lupus nephritis (LN) is estimated to affect more than one-half of Systemic Lupus 
Erythematosus (SLE) patients and is a severe manifestation in SLE Cervera et al 2003 
Immune complex formation in LN is related to a plethora of autoantibodies, especially anti-
double stranded deoxyribonucleic acid (dsDNA) and -nucleosome antibodies, is the result of 
systemic autoimmunity and is a hallmark of the disease (Waldman and Madaio 2005, 
Nowling and Gilkeson 2011) that is generally treated by systemic immunosuppression. Once 
formed, immune complexes activate complement, which can injure renal cells leading to either 
mesangial LN (class I, II), proliferative LN (class III, IV), membranous LN (class V) and 
advanced sclerotic LN (class VI). However, pathogenesis of LN is complex and involves both 
the innate and adaptive immune systems; various cytokines, immune tissues and cell types are 
involved in its pathogenesis. Intra-renal inflammation is maintained via local cytokine and 
chemokine production, and by cells of the innate immune system such as neutrophils, that are 
attracted into the glomerulus and interstitium. Targeting local release of proinflammatory 
cytokines by blocking single cytokine pathways may enhance treatment efficacy in 
autoimmunity without increasing systemic immunosuppression (Allam and Anders 2008, 
Yu et al 2017). 
Lupus nephritis is characterized by glomerular endothelium, podocyte, tubulointerstitial and 
vascular injury. Specific leukocyte subsets, including interleukin 17 (IL-17)-producing T helper 
type 17 (TH17) cells, drive inflammation and contribute to renal immunopathology 
Yu et al 2017. 
Lupus nephritis is categorized histologically into six classes by the International Society of 
Nephrology/Renal Pathology Society (ISN/RPS) classification system (Weening et al 2004, 
Markowitz and D'Agati 2007). Treatments include management with corticosteroids together 
with antimalarials for lower stage disease, followed by more aggressive immunosuppressive 
therapies for more severe disease, and ultimately renal transplant. 
Class III and IV LN are detected in approximately 39 to 71.9% of LN patients and from the 
deposition of immune complexes in the subendothelial space of the glomerular capillaries 
Wang et al 2018. Both these classes of LN are considered to have similar lesions that differ by 
severity and distribution. Class IV diffuse LN is distinguished from class III on the basis of 
involvement of more than 50% of glomeruli with endocapillary lesions. Patients with class III 
and IV LN require aggressive therapy with glucocorticoids and immunosuppressive agents 
including cyclophosphamide (CYC), mycophenolate mofetil (MMF), rituximab as well as 
calcineurin inhibitors (CNIs) Hahn et al 2012. 
With current induction and maintenance therapies, the risk of developing LN-related End Stage 
Renal Disease (ESRD) at 5, 10, and 15 years remained at 11%, 17%, and 22%, respectively 
(Faurschou et al 2010, Tektonidou et al 2016). In addition, current immunosuppressive 
therapies carry substantial infectious as well as other mid/long-term toxicity risks. Despite 
recent advances in treatment for LN, including two recent approvals of belimumab [intravenous 
(i.v.) and subcutaneous (s.c.)], a B-cell activating factor (BAFF) inhibitor and voclosporin 


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(p.o.), a calcineurin inhibitor, it continues to remain a major cause of morbidity and mortality 
(Furie et al 2020, Rovin et al 2021). 
The European League Against Rheumatism/European Renal Association – European Dialysis 
and 
Transplant 
Association 
(EULAR/ERA-EDTA) 
and 
American 
College 
of 
Rheumatology (ACR) guidelines are uniform in their recommendations for therapy for class III 
and IV LN and include a sequence of induction and maintenance phases. For patients with class 
III or IV proliferative glomerulonephritis, the guidelines recommend induction therapy with 
MPA (MMF or enteric-coated MPA sodium) or i.v. CYC, with or without initial pulses of i.v. 
methylprednisolone. With current induction regimens, less than 60% of class III to V patients 
achieve a complete or partial response Appel et al 2009. Among those who attain a complete 
renal response (CRR) with current standard-of-care (SoC), nearly half of the patients had a 
relapse. The incidence rate of relapse in these patients was 5 to 15 per 100 patient year (PY) 
Grootscholten and Berden 2006. 
Despite the aggressive nature of SoC treatment, only up to 30% of patients achieve a CRR after 
1 year Rovin and Parikh 2014. In addition, current LN treatment regimens have substantial side 
effects from glucocorticoids and prolonged immunosuppression Schwartz et al 2014. 
Immunosuppressed LN patients are at significant risk of developing serious infections. In a 
multiethnic Medicaid cohort, the incidence rate of serious infections was more than 2-fold 
higher in LN than in SLE patients Feldman et al 2015. 
In addition to animal models, a growing number of studies in patients with LN indicate that 
IL‑17A and Th17 cells play important roles in the pathogenesis of LN, contributing to 
glomerular injury and the persistence of inflammation and renal damage (Crispín et al 2008, 
Zhang et al 2009). High levels of IL-17 predict poor histopathological outcomes after 
immunosuppressive therapy in patients with LN Zickert et al 2015. A subset of T cells 
infiltrates the kidneys of patients with LN and represent the major source for IL-17 
Crispín et al 2008. IL-17 has the potential to induce the production of additional inflammatory 
cytokines and chemokines and to promote recruitment of inflammatory cells such as monocytes 
and neutrophils to inflamed organs. 
Therefore, a pathogenic model for glomerulonephritis is emerging in which Th17 cells infiltrate 
the kidney and IL-17A (as well as potentially other cytokines) produced by Th17 cells acts 
directly on resident kidney cells to induce cytokines and chemokines that lead to further 
recruitment of Th17 cells and neutrophils into the tissue, resulting in renal tissue damage 
Krebs et al 2017. 
A case report of a patient with refractory LN and concomitant psoriasis vulgaris suggests that 
treatment with the IL-17A inhibitor secukinumab may have contributed to an improvement in 
renal function and a decrease in urine protein levels in this patient Satoh et al 2018.  
A recent case report of a childbearing age women with SLE, who developed refractory LN 
despite all indicated therapeutic options, reported that treatment with IL-17A inhibitor 
secukinumab showed improvement in clinical and biological features and complete renal 
response was achieved Costa R et al 2021. 
Secukinumab is a recombinant high-affinity fully human monoclonal anti-human IL-17A 
antibody of the Immunoglobulin G1 (IgG1)/kappa isotype. The product is indicated in Psoriasis 


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(PsO), Axial Spondyloarthritis (axSpA) and Psoriatic Arthritis (PsA) and has shown to offer 
robust and clinically meaningful efficacy to these patients and is complemented by a 
consistently favorable benefit:risk profile. The safety profile of secukinumab was indeed 
consistent and comparable across PsO, PsA and axSpA, supporting its long-term use in these 
chronic inflammatory conditions. 
Participants from the core trial CAIN457Q12301 study can participate in this optional open-
label extension study as described in Section 1.2. The total duration of the extension study is 
estimated to last about three years providing up to five years of total treatment exposure 
including core study CAIN457Q12301. 
1.2 
Purpose 
This study is an up to three-year open-label extension study to the core study CAIN457Q12301 
(a two-year, phase III study that enrolled participants aged 18 to 75 years with active Lupus 
Nephritis). The aim is to provide treatment with secukinumab delivered subcutaneously (s.c.) 
via pre-filled syringe (PFS) for participants who complete study treatment until the Week 104 
of the core study and opt to continue in to the extension study and to obtain further long-term 
efficacy, safety and tolerability information. 
Background SoC will consist of maintenance therapy with mycophenolic acid (MPA) (which 
refers to mycophenolate mofetil (MMF) (Cellcept® or generic equivalent), or enteric-coated 
MPA sodium (Myfortic® or generic equivalent) at equivalent doses (oral) and oral 
corticosteroids at the minimal dose (could be zero) required by the participant's status to 
maintain response. 
Within this document, at each time MPA will be mentioned without further information, it will 
refer to Cellcept®, Myfortic® or generic equivalent at equivalent doses. 
2 
Objectives, endpoints and estimands 
Table 2-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
● To assess the long-term efficacy of 
secukinumab with respect to CRR over time up 
to Week 260 in adults with Lupus Nephritis 
(ISN/RPS class III or IV, with or without co-
existing class V features) participant on 
background of SoC therapy 
● Proportion of participants achieving CRR 
CRR is a composite endpoint defined as: 
 
● Normal estimated Glomerular Filtration Rate (eGFR) 
or no less than 85% of core Baseline values and 
 
● 24-hour Urine-to-Protein Creatinine Ratio (UPCR) ≤ 
0.5mg/mg 


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2.1 
Primary estimands 
The estimand is the precise description of the treatment effect and reflects strategies to address 
events occurring during trial conduct which could impact the interpretation of the trial results 
(e.g., premature discontinuation of treatment). 
The attributes of the estimand are: 
• Population: All participants who completed secukinumab 300 mg up to Week 104 in core 
study and satisfy the inclusion/exclusion criteria to reflect the targeted LN population 
• Variable: Complete renal response up to Week 260 
• Treatment of interest: secukinumab 300 mg every four weeks and with low dose steroids 
• Remaining intercurrent events: Treatment discontinuation/rescue treatment: composite 
(non-responder) 
• Population level summary: Proportion of responders summarized over time. 


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2.2 
Secondary estimands 
Not applicable 
3 
Study design 
A multicenter, optional, open-label, extension study of s.c. secukinumab to evaluate the long-
term efficacy, safety and tolerability up to three years in patients with lupus nephritis. 
The aim of this three-year extension study is to provide treatment with secukinumab for 
participants who complete core study treatment in CAIN457Q12301 and to obtain further long-
term efficacy, safety and tolerability information. 
Investigators will use their clinical judgement to decide if it might be beneficial, in terms of 
overall improvement and response to therapy, for participants to enter the extension study. The 
total combined duration for the core study and this extension study is five years. 
At Week 104 of the core study CAIN457Q12301, eligible participants will complete the 
assessments associated with the core study visit and will subsequently continue in the extension 
study on the dose of secukinumab 300 mg administered every four weeks. 
Of note, as this is an extension study, Baseline always refers to the core study CAIN457Q12301 
Baseline. 
An outline of study design is presented in Figure 3-1 and a detailed visit and assessment 
schedule in Table 8-1. 
Additional unscheduled follow-up visits in person and/or by phone may be performed as per 
investigator's clinical judgement. 
Figure 3-1 
Study Design 
  


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4 
Rationale 
4.1 
Rationale for study design 
This three-year open-label extension study will offer continuous secukinumab therapy to 
eligible participants from the core study CAIN457Q12301 and will provide long-term efficacy 
and safety data. The regular assessments of disease activity would ensure that participants who 
are experiencing worsening of disease can exit the study upon their own decision or based on 
the advice of the investigator at any time. 
4.1.1 
Rationale for choice of background therapy 
The SoC background therapy that all participants will receive was selected as it corresponds to 
the treatment recommendations of the ACR and EULAR/ERA-EDTA guidelines for 
maintenance therapy for participants with ISN/RPS Class III or IV LN, with or without co-
existing class V features (Bertsias et al 2012, Hahn et al 2012, Palmer et al 2017). 
SoC background regimen will consist of MPA along with oral corticosteroids at the minimum 
dose (could be zero) required by the participant status to maintain response and shall not 
exceed >7.5 mg/day (prednisone or equivalent). 
4.2 
Rationale for dose/regimen and duration of treatment 
The doses and regimen selected for the core study CAIN457Q12301 are projected to deliver 
efficacy while at the same time ensuring participant safety. 
The proposal to continue treatment with subcutaneous (s.c.) doses of 300 mg administered every 
four weeks, is based on the need for long-term treatment exposure in participants suffering from 
a chronic illness such as LN with relapsing and remitting course. 
Subcutaneous injection through PFS offers the option of self-administration by the participant 
and is likely to provide a better treatment experience and added convenience. Participants with 
chronic diseases who are able to self-inject their medication gain control of their treatment 
schedule and their treatment setting, thus allowing greater independence, better adherence, 
improved therapeutic outcomes and freedom in their social, domestic, and professional lives, 
which can result in economic benefits to both participants and the healthcare system 
(Kivitz et al 2006, Chilton and Collett 2008). Self-injection may also offer psychological 
benefits over administration by healthcare professionals, including improved self-esteem 
Hamm R et al 2000. 
4.3 
Rationale for choice of control drugs (comparator/placebo) or 
combination drugs 
There is no placebo control group or active comparator in this study given the purpose and main 
objectives. 
4.4 
Purpose and timing of interim analyses/design adaptations 
Interim analyses may be performed for purposes of publication and/or to support health 
authority interactions, as necessary. 


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4.5 
Risks and benefits 
To date, belimumab and voclosporin are two recently approved drugs available for lupus 
nephritis 
patients. 
Current 
standard 
of 
care 
therapies 
comprise 
conventional 
immunosuppressants which are not fully efficacious in all patients and associated with 
significant toxicities. Based on the scientific rationale for targeting IL-17 pathway in lupus 
nephritis, and the data available on secukinumab, IL-17 inhibition by secukinumab has a 
potential therapeutic benefit for lupus nephritis patients who are clinically active despite 
standard of care treatment. 
Secukinumab has demonstrated positive benefit:risk in the treatment of multiple chronic 
inflammatory diseases, including PsA, axSpA and PsO. 
Secukinumab therapy has a well-established and well-described safety profile based on 
extensive post-marketing experience and continued clinical trial patient exposure since its 
approval for the first indication of moderate to severe plaque psoriasis. Details of the risk and 
benefits are outlined in the current version of the Investigator's Brochure. 
The safety and tolerability of secukinumab as an add-on to SoC will be evaluated. Based on the 
favorable safety profile of secukinumab and the known safety profile of the SoC treatments for 
LN, it is unlikely that the addition of secukinumab to the LN SoC regimens will result in 
unacceptably high risks, particularly for serious infections. 
The risk to participants in this trial may be minimized by compliance with the eligibility criteria 
and study procedures, as well as close clinical monitoring, and periodic review of safety data 
by an independent Data Monitoring Committee (DMC). Additional information can be found 
in the IB for secukinumab. 
Women of childbearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study, and must agree that in 
order to participate in the study, they must adhere to the contraception requirements outlined in 
the exclusion criteria. If there is any question that the participant will not reliably comply, they 
should not be entered or continue in the study. 
From the standpoint of the overall risk-benefit assessment, the current trial with secukinumab 
is justified. 
4.6 
Rationale for Public Health Emergency mitigation procedures 
During a Public Health emergency as declared by Local or Regional authorities i.e. pandemic, 
epidemic or natural disaster, mitigation procedures to ensure participant safety and trial integrity 
are listed in relevant sections. Notification of the Public health emergency should be discussed 
with Novartis prior to implementation of mitigation procedures, and permitted/approved by 
Local or Regional Health Authorities and Ethics Committees as appropriate. 
5 
Study Population 
The study population will consist of male and female participants aged from 18 to 75 years who 
were diagnosed with active LN-World Health Organization (WHO) or ISN/RPS Class III or IV 
[excluding III (C), IV-S (C) and IV-G (C)], with or without co-existing class V features 


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at SCREENING in the core study CAIN457Q12301, and who have completed the 
entire treatment period up to and including Week 104 of the core study. 
5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must meet all of the following criteria: 
1. Participant must have both participated in core study and completed the entire treatment 
period up to and including Week 104 of the core study CAIN457Q12301. 
2. Participant must be deemed by the investigator to benefit from secukinumab therapy. 
3. Signed informed consent must be obtained prior to participation in the study. 
5.2 
Exclusion criteria 
Participants meeting any of the following criteria are not eligible for inclusion in this study.  
1. Any participant taking other concomitant biologic immunomodulating agent(s) except 
secukinumab. 
2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive hCG 
laboratory test. 
3. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using highly effective methods of contraception 
during the entire study or longer if required by locally approved prescribing information 
(e.g., in European Union (EU) 20 Weeks). Highly effective methods are recommended 
due to the known teratogenic effect of SoC (MPA). 
Highly effective contraception methods include: 
• Total abstinence, when this in line with the preferred and usual lifestyle of the 
participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception. 
• Female sterilization (have had surgical bilateral oophorectomy [with or without 
hysterectomy], total hysterectomy or tubal ligation. In case of oophorectomy alone, 
only when the reproductive status of the woman has been confirmed by follow-up 
hormone level assessment  
• Male sterilization (at least 6 months prior to screening). For female participants on the 
study, the vasectomized male partner should be the sole partner for that participant 
• Barrier methods of contraception: Condom or occlusive cap (diaphragm or 
cervical/vault caps). NOTE: for United Kingdom: with spermicidal 
foam/gel/film/cream/vaginal suppository 
• Use of oral (estrogen and progesterone), injected or implanted hormonal methods of 
contraception or other forms of hormonal contraception that have comparable efficacy 
(failure rate <1%), for example hormone vaginal ring or transdermal hormone 
contraception or placement of an intrauterine device (IUD) or intrauterine system 
(IUS). In case of use of oral contraception, women of childbearing potential should 
have been stable on the same pill for a minimum of 3 months before taking study 
treatment. 


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In case local regulations deviate from the contraception methods listed above, local 
regulations apply and will be described in the informed consent form (ICF). 
If stricter female or male contraception requirements are specified in the country-specific 
label for maintenance standard of care medications, they must be followed. 
Note: Women are considered post-menopausal if they have had 12 months of natural 
(spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, 
history of vasomotor symptoms). Women are considered not of child bearing potential if 
they are post-menopausal or have had surgical bilateral oophorectomy (with or without 
hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of 
oophorectomy alone, only when the reproductive status of the woman has been confirmed 
by follow-up hormone level assessment is she considered not of child bearing potential. 
6 
Treatment 
6.1 
Study treatment 
Before enrollment in this extension study, all participants electing to continue will sign an ICF. 
Detailed instructions, based on the Instructions for Use (IFU), for self-administration of the s.c. 
injection using the PFS formulation will be provided to each participant. Each injection will be 
administered into an appropriate injection site of the body. For the first visit at Week 104E1, 
s.c. administration will be performed at site under the supervision of the site staff. Starting from 
Week 112, participants will have the choice of self-administration at home or continuing with 
administration at site, based on personal preference and the investigator’s clinical judgment. 
Site staff will administer the injection to participants who are not able or feel insecure to self-
administer the PFS injection. 
At Week 104, all eligible participants from the core study can opt to be enrolled in the extension 
study via Interactive Response Technology (IRT) and will receive secukinumab dosing, 300 
mg every four weeks until Week 256. The Week 104E1 will be performed on the same day 
once the participant completes Week 104 of the core study.  
The investigator or his/her delegate will contact the IRT after confirming that the participant 
fulfills all the inclusion/exclusion criteria. The IRT will then specify a unique medication 
number for the first package of investigational treatment to be dispensed to the participant for 
Week 104E1. 
6.1.1 
Investigational and control drugs 
Novartis Global Clinical Supply (GCS) will supply the following study drugs: 
Table 6-1 
Investigational drug and Control drug 
Investigational  
(Name and 
Strength) 
Pharmaceutical 
Dosage Form 
Route of 
Administration 
Presentation 
Sponsor (global or 
local) 
AIN457300 mg 
/2mL 
Solution for 
injection in pre-filled 
syringe 
Subcutaneous use 
Open label prefilled 
syringes (PFS) 
Novartis Pharma 
AG 


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The PFSs are packed in an open-label fashion and do not need to be prepared.  
Each study site will be supplied by Novartis with investigational treatment in packaging of 
identical appearance. The investigational treatment packaging has a two-part label. A unique 
medication number is printed on each part of this label. 
The study treatments will be labeled as follows: AIN457 300mg/2mL. 
6.1.2 
Additional study treatments 
No other study treatment beyond investigational drug and control drug are included in this trial. 
6.1.3 
SoC background therapy 
All participants will receive SoC background regimen for maintenance therapy. 
Background SoC medications will not be provided by Novartis GCS and must be handled at 
the country level. Oral doses of MPA or corticosteroids will be taken by the participant at home. 
Table 6-2 
Background therapy 
Name of medication 
Dosage form 
Route of administration 
Availability 
MMF/MPA 
Tablet 
Oral 
Open-label participant packs 
Corticosteroids 
Tablets  
Oral 
Open-label participant  packs 
6.1.3.1 
Maintenance therapy 
The participants shall continue the same dose of MPA as administered in the core study. The 
target dose during the maintenance period is 1-2 g/day of MMF or of equivalent dosage of 
enteric-coated MPA. Further reduction of MMF to 0.5 g/day or of equivalent dosage of enteric-
coated MPA is allowed as per Investigator's decision. 
Oral corticosteroids shall continue at the minimum dose (could be zero) required by the 
participant status to maintain response and shall not exceed >7.5 mg/day (prednisone or 
equivalent). 
6.1.4 
Treatment arms/group 
All participants will be treated with open label secukinumab 300 mg every four weeks until 
Week 256. 
6.1.5 
Treatment duration 
The total duration of the extension study is estimated to last up to three years, providing up to 
five years of total treatment exposure including core study CAIN457Q12301. 
Participants may be discontinued from treatment earlier due to unacceptable toxicity, disease 
progression and/or treatment is discontinued at the discretion of the investigator or the 
participant, or if the clinical trial is discontinued for any reason. Participants who the 
investigator believes will continue to receive benefit from treatment may also have post-trial 
access until secukinumab is available for LN following product launch/subsequent 
reimbursement (where applicable), or treatment discontinuation, or the benefit-risk profile is no 
longer positive. 


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6.2 
Other treatment(s) 
6.2.1 
Concomitant therapy 
All medications, procedures, and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the participant was enrolled into the study must be 
recorded on the appropriate Case Report Forms (CRFs). 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt, the investigator should contact the Novartis medical monitor before 
allowing a new medication to be started or to determine if the participant should continue 
participation in the study. 
6.2.1.1 
Permitted concomitant therapy requiring caution and/or action 
Guidelines for the use of specific medications are provided below. 
Participants may continue on the concomitant medication listed below if prescribed in the core 
study. However, investigators may change the dose of concomitant medications during the 
study for safety reasons based on their clinical judgement. Each concomitant medication should 
be captured/recorded in the electronic Case Report Form (eCRF) at every visit, including the 
dose changes when appropriate. 
Anti-malarial medications 
Concomitant treatment with anti-malarial (e.g., hydroxychloroquine) will continue if prescribed 
in the core study and will be recorded in the eCRF. 
Anti-hypertensive medications 
Participants already taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin 
receptor blockers (ARBs) in the core study should remain on the same dose throughout the 
study unless precluded by toxicity or if dose adjustment is required for hypertensive control. 
Combination therapy with an ACE inhibitor and an ARB will not be allowed. 
Cholesterol-lowering drugs 
Concomitant treatment with cholesterol-lowering drugs (e.g., statins) will continue if prescribed 
in the core study and will be recorded in the eCRF. Statin treatment can be initiated during the 
course of the study if considered required by the Investigator. 
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 
NSAIDs may have impact upon renal function and therefore should not be used during the trial 
with the following exceptions: 
• treatment of pleuritis and pericarditis if deemed necessary by the Investigator. 
• treatment of arthritis pain that is unresponsive to other treatment modalities (e.g., 
analgesics, intra-articular steroid treatment) 


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Osteoporosis Prevention /Treatment 
Participants not already taking vitamin D (400 IU/day) and calcium supplements (1200 mg/day 
of calcium citrate or 1500 mg/day calcium carbonate) in the core study are allowed to start these 
medications, at the investigator’s discretion (see ACR Ad Hoc Committee 2001). 
Other Permitted Therapy 
Low dose aspirin for cardioprotection may be used at Investigator’s discretion. 
Participants who use oral contraceptives or hormone-replacement therapy should continue their 
use. 
All other concomitant medications deemed necessary will be reviewed by the Investigator in 
consultation with the Novartis Clinical Team and decisions made on a case-by-case basis. 
Note: Concomitant medications will not be provided by Novartis and must be supplied by the 
study center. 
6.2.2 
Prohibited medication 
The following treatments are prohibited during the course of the trial due to their mechanisms 
of action that can confound the study results. If administered, the participant is to be withdrawn 
from the study treatment:  
• Initiation of cyclophosphamide, CNI, rituximab and belimumab therapy 
• Use of any other systemic biologic/non-biologic immunomodulatory treatment 
• Administration of live vaccines 
• Any investigational treatment or participation in any interventional trial. 
6.2.3 
Rescue medication 
Rescue medication is defined as any new medication used because the participant's disease is 
not adequately controlled by secukinumab in addition to the SoC background therapy. 
Although no participant will be restricted from receiving necessary rescue medications for lack 
of benefit or worsening of the disease (e.g., experiencing a renal flare), participants will be 
discontinued from the study medication if they are treated with prohibited medications (as 
described in Section 6.2.2). The choice of the rescue medication will be based on the treating 
Investigator's assessment and applicable regulatory guidelines. 
If study investigational treatment is discontinued, participants may take study prohibited 
medication under the Investigator's guidance and as per locally approved prescribing 
information. 
Participant will be discontinued from the study and complete Week 260/End of Treatment 
(EOT) visit if treated with prohibited medications (as described in Section 6.2.2) and should 
complete the End of Treatment (EOT) visit at the earliest possible time point and enter the Post-
treatment follow-up period.  
A follow-up visit is to be done 12 weeks after last study treatment administration for all 
participants, regardless of whether they complete the entire study as planned or discontinue 
prematurely. 


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Use of rescue medication must be recorded on the appropriate eCRF page. 
6.3 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described under investigational 
section. 
A unique medication number is printed on the study medication label. 
Investigator staff will identify the study medication kits to dispense to the participant by 
contacting the IRT and obtaining the medication number(s). The study medication has a 2-part 
label (base plus tear-off label). Immediately before dispensing the medication kit to the 
participant, site personnel will detach the outer part of the label from the packaging and affix it 
to the source document. 
As per Section 4.6, during a Public Health emergency as declared by Local or Regional 
authorities i.e. pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, 
delivery of investigational medicinal product (IMP) directly to a participant's home may be 
permitted (if allowed by Local or Regional Health Authorities and Ethics Committees as 
appropriate) in the event the Investigator has decided that an on-site visit by the participant is 
no longer appropriate or possible, and that it is in the interest of the participant's health to 
administer the study treatment even without performing an on-site visit. The dispatch of IMP 
from the site to the participant’s home remains under the accountability of the Investigator. 
Each shipment/provisioning will be for a maximum of 24 weeks supply. In this case, regular 
phone calls or virtual contacts (every four weeks or more frequently if needed) will occur 
between the site and the participant for instructional purposes, safety monitoring, investigation 
of any adverse events, ensuring participants continue to benefit from treatment, and discussion 
of the participant's health status until the participants can resume visits at the study site. 
6.3.1 
Handling of study treatment and other treatment 
6.3.1.1 
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the labels. 
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis Country Organization (CO) Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about 
the participant except for the medication number. 
The PFS sealed in their outer box must be stored in an access-controlled/locked refrigerator 
between 2°C and 8°C (36°F and 46°F) (Do Not Freeze) and protected from light. They must be 
carefully controlled in accordance with regulations governing investigational medicinal 
products and local regulations. 


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If the participant will be self-administering treatment at home, the investigator should ensure 
the participants can store the medication according to these conditions before allowing the 
participant to self-administer at home. 
If required for certain participants, treatment might be administered at home by an off-site 
healthcare professional (OHP). 
The investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
field monitors during site or remote monitoring visits, and at the completion of the trial. 
If study treatment is administered at home, participants will be asked to return all unused study 
treatment and packaging at the next site visit, at the end of the study or at the time of 
discontinuation of study treatment. 
Subcutaneous administration with PFSs 
The study treatment solution must be injected into non-affected areas of the skin. 
The injections will be self-administered into the appropriate site of the body (thighs, arms, 
abdomen), and each injection should be given at a different injection site to reduce the risk of 
reaction. If participant chooses the abdomen, a two-inch (5 cm) area around the navel should 
be avoided. Investigational drug should not be injected into areas where the skin is tender, 
bruised, red, or hard, or where participant has scars or stretch marks. 
The site may destroy and document destruction of unused study treatment, drug labels and 
packaging as appropriate in compliance with site processes, monitoring processes and per local 
regulation/guidelines, and after approval by the Novartis Clinical Team. Otherwise, the 
investigator will return all unused study treatment, packaging, drug labels, and a copy of the 
completed drug accountability log to the Novartis monitor or to the Novartis address provided 
in the investigator folder at each site. 
The treatment for remote administration might be handled by off-site healthcare provider such 
as off-site research nurse, in line with the IFU. 
6.3.1.2 
Handling of other treatment 
The following non-study treatment has to be monitored specifically: 
• SoC background therapy, as described in Section 6.1.3, 
• Concomitant therapy as described in Section 6.2.1, e.g., anti-malarial medications, ACE 
inhibitors or ARBs. 
6.4 
Participant numbering, treatment assignment, randomization 
6.4.1 
Participant numbering 
This being an extension study, the participant numbers will remain same as that of core study 
CAIN457Q12301, new numbers will not be assigned. 
Each participant is identified in the study by a Participant Number (Participant No.), that is 
assigned when the participant is first enrolled in the core study CAIN457Q12301 and is retained 
for the participant throughout his/her participation in the trial. The Participant No. consists of 


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the Center Number (Center No.) (as assigned by Novartis to the investigative site) with the 
sequential participant number suffixed to it assigned in the core study, so that each participant’s 
participation is numbered uniquely across the entire database. 
6.4.2 
Treatment assignment, randomization 
At visit Week 104E1, all eligible participants from core study CAIN457Q12301 will be enrolled 
via Interactive Response Technology (IRT). The investigator or his/her delegate will contact 
the IRT after confirming that the participant fulfills all the inclusion/exclusion criteria. The IRT 
will specify a unique medication number for the first package of study treatment to be dispensed 
to the participant. 
A separate medication list will be produced by or under the responsibility of Novartis Global 
Clinical Supply (GCS) using a validated system that automates the assignment of medication 
numbers to packs containing the study treatment. 
6.5 
Treatment blinding 
There is no treatment blinding in this study. Participants, investigator staff and persons 
performing the assessments will remain blinded to the identity of the treatment that participants 
were randomized to within the core study CAIN457Q12301 from the time of enrollment in the 
extension study until the final database lock of the core study. 
6.6 
Dose escalation and dose modification 
While no study treatment dose adjustments are permitted, interruptions are allowed as described 
below in Section 6.6.2. 
6.6.1 
Definitions of dose limiting toxicities (DLTs) 
Not applicable. 
6.6.2 
Dose modifications 
Study treatment interruption is only permitted if, in the opinion of the investigator, a participant 
is deemed to be placed at a significant safety risk unless dosing is temporarily interrupted. In 
such cases, study treatment should be interrupted only during the time that this risk is present 
and ongoing. Study treatment can be restarted at the next scheduled visit after resolution of the 
safety risk. 
Any study treatment interruption must be recorded on the appropriate CRF. 
6.6.3 
Follow-up for toxicities 
Participants whose treatment is interrupted or permanently discontinued due to an adverse event 
or clinically significant laboratory value, must be followed up in accordance with what is 
clinically indicated per the investigator until resolution or stabilization of the event. Appropriate 
clinical experts such as ophthalmologist, endocrinologist, dermatologist, psychiatrists, etc., 
should be consulted as deemed necessary. All participants must be followed up for adverse 
events and serious adverse events for 84 days following the last dose of study treatment. 


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6.7 
Additional treatment guidance 
6.7.1 
Treatment compliance 
The first study treatment administration will occur at the Week 104E1 visit only after eligibility 
criteria have been confirmed, all study assessments have been performed, and the scheduled 
blood samples have been drawn. 
All dates and times of study treatment administration will be recorded on the appropriate 
Dosage Administration Record eCRF page. 
6.7.1.1 
Study treatment compliance 
Compliance is expected to be 100% unless temporary interruption is needed for safety reasons 
as described in Section 6.6.3. 
For home administration, the investigator must promote compliance by instructing the 
participant to take the study treatment exactly as prescribed and by stating that compliance is 
necessary for the participant’s safety and the validity of the study. The participant must also be 
instructed to contact the investigator if he/she is unable for any reason to take the study 
treatment as prescribed. Compliance will be assessed by the investigator and/or study personnel 
at each visit checking the Participant Dosing Record, unused syringes with boxes and empty 
syringe boxes and reviewing information provided by the participant. 
Detailed instructions, based on the Participant Instructions for Home Administration, for self-
administration at home of the s.c. injection using the PFS formulation will be provided to each 
participant. This information should be captured in the source document at each visit. 
All study treatment dispensed and returned must be recorded in the Drug Accountability Log. 
6.7.1.2 
Standard of care treatment compliance 
Oral doses of MPA or corticosteroids, as specified in Section 6.1.3, will be taken by the 
participant at home. 
Doses administered and dates (MPA/Corticosteroids) should be recorded on the appropriate 
eCRF pages. 
The investigator must promote compliance by instructing the participant to take the SoC 
treatment exactly as prescribed and by stating that compliance is necessary for the participant’s 
safety and the validity of the study. The participant must also be instructed to contact the 
investigator if he/she is unable for any reason to take the SoC treatment as prescribed. 
Compliance will be assessed by the investigator and/or study personnel at each visit by 
reviewing the information provided by the participant. This information should be captured in 
the source document at each visit. 
6.7.2 
Recommended treatment of adverse events 
Treatment for AEs are at the discretion of the investigator or treating physician. Refer to the 
Investigator's Brochure for AEs related to secukinumab. 


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At present there is insufficient information to provide specific recommendations regarding 
treatment of adverse events (AEs). 
Medication used to treat adverse events (AEs) must be recorded on the appropriate CRF. 
6.7.3 
Emergency breaking of assigned treatment code 
Not applicable 
7 
Informed consent procedures 
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation), Institutional Review Board(IRB)/Independent Ethics Committee 
(IEC)-approved informed consent. 
If applicable, in cases where the participant's representative(s) gives consent (if allowed 
according to local requirements), the participant must be informed about the study to the extent 
possible given his/her level of understanding. If the participant is capable of doing so, he/she 
must indicate agreement by personally signing and dating the written informed consent 
document. 
Informed consent must be obtained before conducting any study-specific procedures (e.g. all of 
the procedures described in the protocol). The process of obtaining informed consent must be 
documented in the participant source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent form 
that complies with the International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6 Good Clinical Practice (GCP) guidelines and 
regulatory requirements and is considered appropriate for this study. Any changes to the 
proposed consent form suggested by the investigator must be agreed by Novartis before 
submission to the IRB/IEC. 
Information about common side effects already known about the investigational treatment can 
be found in the Investigator's Brochure (IB). This information will be included in the participant 
informed consent and should be discussed with the participant during the study as needed. Any 
new information regarding the safety profile of the investigational drug that is identified 
between IB updates will be communicated as appropriate, for example, via an investigator 
notification or an aggregate safety finding. New information might require an update to the 
informed consent and then must be discussed with the participant. 
The following informed consents are included in this study: 
• Main study consent, which also included:  
• A subsection that requires a separate signature for the ‘Optional Consent for 
Additional Research’ to allow future research on data/samples collected during this 
study 
• As applicable, Pregnancy Outcomes Reporting Consent for female participants t 
Women of child bearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order 
to participate in the study they must adhere to the contraception requirements. 


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A copy of the approved version of all consent forms must be provided to Novartis after IRB/IEC 
approval. 
As per Section 4.6, during a Public Health emergency as declared by Local or Regional 
authorities i.e. pandemic, epidemic or natural disaster, that may challenge the ability to obtain 
a standard written informed consent due to limits that prevent an on-site visit, Investigator may 
conduct the informed consent discussion remotely (e.g. telephone, videoconference) if 
allowable by a local Health Authority. 
Guidance issued by local regulatory bodies on this aspect prevail and must be implemented and 
appropriately documented (e.g., the presence of an impartial witness, sign/dating separate ICFs 
by trial participant and person obtaining informed consent, etc.). 
8 
Visit schedule and assessments 
The Assessment Schedule Table 8-1 lists all of the assessments when they are performed. All 
data obtained from these assessments must be supported in the participant’s source 
documentation. 
Participants should be seen for all visits/assessments as outlined in the assessment schedule 
Table 8-1 or as close to the designated day/time as possible. Missed or rescheduled visits should 
not lead to automatic discontinuation. 
Participants who discontinue from study treatment are to return for the end of treatment visit as 
soon as possible and attend the follow-up visits as indicated in the Assessment Schedule. 
Participants who discontinue from study or withdraw their consent/oppose the use of their 
data/biological samples should be scheduled for a final evaluation visit if they agree, as soon as 
possible, at which time all assessments listed for the final visit will be performed. At this final 
visit, all dispensed investigational product should be reconciled, and the adverse event and 
concomitant medications not previously reported must be recorded on the CRF. 
The “X” in the table denotes the assessments to be recorded in the clinical database or received 
electronically from a vendor. The “S” in the table denotes the assessments that are only in the 
participant’s source documentation and do not need to be recorded in the clinical database. 
As per Section 4.6, during a Public Health emergency as declared by Local or Regional 
authorities i.e., pandemic, epidemic or natural disaster that limits or prevents on-site study visits, 
alternative methods of providing continuing care may be implemented by the investigator as 
the situation dictates. If allowable by a local Health Authority and depending on operational 
capabilities, phone calls, virtual contacts (e.g., tele consult) or visits by site staff/ home nursing 
staff to the participant´s home, can replace on-site study visits, for the duration of the disruption 
until it is safe for the participant to visit the site again. 


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Table 8-1 
Assessment Schedule 
Period 
Extension Treatment Year 1 
Visit Name 
W104E1 
W108 
W112 
W116 
W120 
W124 
W128 
W132 
W136 
W140 
W144 
W148 
W152 
W156 
Visit Numbers1 
100 
110 
120 
130 
140 
150 
160 
170 
180 
190 
200 
210 
220 
230 
Days 
0  
28 
56 
84 
112 
140 
168 
196 
224 
252 
280 
308 
336 
364 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
Inclusion / Exclusion criteria 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
Participant details entry in 
extension database 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
Site Visit (mandatory) 
X 
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Study Drug Administration at 
site2 
X 
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Study Drug Administration at 
home2,3 
  
  
X 
X 
  
X 
X 
  
X 
X 
  
X 
X 
  
Standard of Care 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications/non-drug 
therapies 
Update as necessary 
Physical Examination 
  
S 
  
  
S 
  
  
S 
  
  
S 
  
  
S 
Vital Signs 
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Body Weight9 
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
12-Lead ECG (local) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology 
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Clinical Chemistry 
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Coagulation Panel 
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Fasting lipid panel4 
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
24-hr urine collection 
(UPCR
) 
  
  
  
  
  
  
  
X5 
  
  
  
  
  
X5 
FMV urine collection 
(central/local assessments)6 
  
X 
  
  
X 
  
  
X 
  
  
X 
  
  
X 
Pregnancy test (urine)7 
  
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Adverse Events8 
Update as necessary 
 


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Period 
Extension Treatment Year 2 
Visit Name 
W160 
W164 
W168 
W172 
W176 
W180 
W184 
W188 
W192 
W196 
W200 
W204 
W208 
Visit Numbers1 
240 
250 
260 
270 
280 
290 
300 
310 
320 
330 
340 
350 
360 
Days 
392 
420 
448 
476 
504 
532 
560 
588 
616 
644 
672 
700 
728 
Site Visit (mandatory) 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
Study Drug Administration 
at site2 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
Study Drug Administration 
at home2,3 
X 
X 
X 
X 
X 
  
X 
X 
X 
X 
X 
X 
  
Standard of Care 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications/non-drug 
therapies 
Update as necessary 
Physical Examination 
  
  
  
  
  
S 
  
  
  
  
  
  
S 
Vital Signs 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
Body Weight9 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
Hematology 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
Clinical Chemistry 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
Coagulation Panel 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
Fasting lipid panel4 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
24-hr urine collection 
(UPCR/
) 
  
  
  
  
  
X5 
  
  
  
  
  
  
X5 
FMV urine collection 
(central/local 
assessments)6 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
Pregnancy test (urine)7 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Adverse Events8 
Update as necessary 
 


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Period 
 
Extension Treatment Year 3 
Visit Name 
W212 
W216 
W220 
W224 
W228 
W232 
W236 
W240 
W244 
W248 
W252 
W256 
W260/EOT 
Unscheduled10 
W268/EOS/Follow 
up11 
Visit Numbers1 
370 
380 
390 
400 
410 
420 
430 
440 
450 
460 
470 
480 
490 
500 
1999 
Days 
756 
784 
812 
840 
868 
896 
924 
952 
980 
1008 
1036 
1064 
1092 
1093 
1148 
Site Visit 
(mandatory) 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Study Drug 
Administration at 
site2 
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
Study Drug 
Administration at 
home2,3 
X 
X 
X 
X 
X 
  
X 
X 
X 
X 
X 
X 
  
  
  
Standard of Care 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications/non-
drug therapies 
Update as necessary 
Physical 
Examination 
  
  
  
  
  
S 
  
  
  
  
  
  
S 
S 
S 
Vital Signs 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Body Weight9 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Hematology 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Clinical Chemistry 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Coagulation Panel 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Fasting lipid panel4 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
X 
X 
24-hr urine 
collection 
(UPCR
) 
  
  
  
  
  
X5 
  
  
  
  
  
  
X5 
X 
  
FMV urine 
collection 
(central/local 
assessments)6 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Pregnancy test 
(urine)7 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Adverse Events8 
Update as 
necessary 
Update as necessary 
X 
X 


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X Assessment to be recorded in the clinical database or received electronically from a vendor 
S Assessment to be recorded in the source documentation only 
1 Visit structure given for internal programming purpose only 
2 IRT to be contacted based on type of visit • For site administration: Contact IRT every visit • 
For home administration: Contact IRT at the previous visit and 
collect drug for subsequent home visits 
3 Participants who are unable to self-administer the PFS injection at home, will visit the site and site staff will administer PFS injection for them or get administration at 
home by an off-site healthcare provider 
4 Samples for lipid panel should be obtained after an overnight fast (10hrs or more) 
5 Site to ensure that a urine container is dispensed at previous site visit 
6 First morning void urine sample will be collected for 1) local determination of urinary sediment and standard safety evaluation 2) central determination of UPCR 3) 
pregnancy test where applicable. Jugs for the Urine collection will be dispensed at previous visit 
7 Pregnancy tests will be conducted for women of childbearing potential. Only if positive pregnancy urine dipstick test, samples to be collected and shipped to central 
lab 
8 AEs/SAEs occurring after the participant has provided informed consent must be reported 
9 Body Mass Index (BMI) to be automatically calculated by Novartis 
10 As per site requirements 
11 If participant decides to discontinue study at any point of time, the participant would need to complete the follow up visit 12 weeks after the last dose 


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8.1 
Enrollment 
At Week 104 all eligible participants from the core study can opt to be enrolled in the extension 
study via Interactive Response Technology (IRT). 
The Week 104E1 will be performed on the same day once the Week 104 is completed by 
the participant. Participant must be able to understand and communicate with investigator and 
comply with the requirements of the study and must give a written, dated and signed informed 
consent before any extension study assessments are performed. 
The investigator or his/her delegate will contact IRT after confirming that participant fulfills all 
inclusion/exclusion criteria. The IRT will then specify a unique medication number for the first 
package of the investigational treatment to be dispensed to a participant at Week 104E1. 
8.2 
Screening 
8.2.1 
Information to be collected on screening failures 
Not Applicable 
8.3 
Participant demographics/other Baseline characteristics 
Participant's demographic and Baseline characteristics will not be separately captured in the 
extension database, participant number from the core study CAIN457Q12301 will be the only 
information captured.  
Of note, as this is an extension study, Baseline always refers to the core study CAIN457Q12301 
Baseline. 
8.4 
Efficacy 
Clinical efficacy measurements related to primary 
 are described in 
the subsections below. 
8.4.1 
Complete Renal Response (CRR) 
The CRR will be used to determine efficacy. A participant is defined as a CRR responder when 
the following two conditions are met. 
• Estimated glomerular filtration rate (eGFR) is within the normal range or no less than 85% 
of Baseline 
and 
• 24-hour urinary protein to creatinine ratio (UPCR) ≤ 0.5 mg/mg 
 
 


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8.4.3 
Estimated Glomerular Filtration Rate (eGFR) 
The glomerular filtration rate will be estimated using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) equation Martínez-Martínez MU et al 2013 (see 
appendix Section 16.3) based on participant gender, age (years) and serum creatinine (mg/dL). 
Central laboratory serum creatinine values will be used for all renal function data analysis. 
8.4.4 
Urine Protein-to-Creatinine Ratio (UPCR) 
Urine Protein-to-Creatinine Ratio (UPCR), expressed in mg/mg, will be determined by a central 
laboratory by dividing the protein concentration by the creatinine concentration as measured in 
the urine collected. 
Depending on the objective to be assessed, the UPCR will be determined using one of the 
following two types of urine collection, 24-hour urine collection or first morning void urinary 
sample, as indicated in Section 2, Table 2-1, Objectives and related endpoints. 
Both the 24-hour urine collection and the first morning void will be collected in the participant's 
home. 
 
 
8.4.6 
Appropriateness of efficacy assessments 
The 
proposed 
primary 
endpoint 
is 
in 
line 
with 
the 
Committee for Medicinal Products for Human Use 2015 guideline, which recommends that 
studies conducted in patients with LN should be aimed for the control of renal activity with 
primary outcome focusing on renal specific endpoints such as induction of CRR. 
The CRR is demonstrated as a clinically significant improvement of renal function as measured 
by improvement of eGFR (normalization/return to Baseline eGFR), and a reduction in renal 
injury as measured by reduction in proteinuria (<0.5 mg/mg in 24-hour) and absence of urinary 
sediment. The urinary sediment was removed from the components of the primary endpoint 
CRR after consultation of Food and Drug Administration (FDA) and European Medicines 
Agency (EMA), due to the difficulty to standardize methods of evaluation for urinary sediment 
across a multicenter study, and because the selection of the appropriate population (active class 
III or IV LN) is ensured by renal biopsies performed within six months of enrollment in core 
study CAIN457Q12301. 
 
 


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In addition, both CRR 
 have been previously used in clinical trials in LN, as a measure 
of the renal activity and are the endpoints used in the core study CAIN457Q12301, allowing an 
evaluation of long-term efficacy, safety and tolerability. 
8.5 
Safety 
All blood draws and safety assessments should be done prior to study treatment administration. 
Appropriate safety assessments (e.g., evaluation of AEs and SAEs) should be repeated after the 
dose is administered. 
• Physical examination 
• Vital signs 
• Weight 
• Laboratory evaluations (Hematology, Clinical Chemistry, Lipid Panel, Urinalysis) 
• Evaluation of AEs/SAEs 
• Electrocardiogram 
• Local tolerability (Injection site reactions) 
• Pregnancy 
• Tolerability of secukinumab 
As per Section 4.6, during a Public Health emergency, as declared by Local or Regional 
authorities i.e. pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, 
regular phone or virtual calls can occur (every four weeks or more frequently if needed) for 
safety monitoring and discussion of the participant´s health status until it is safe for the 
participant to visit the site again. 
Table 8-2 
Assessments specifications 
Assessment 
Specification 
Physical 
examination 
A complete physical examination done at Week 104E1 visit will include the examination of 
general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, lungs, heart, 
abdomen, back, lymph nodes, extremities, vascular, and neurological systems. At 
subsequent visits, a short physical exam will include the examination of general appearance 
and vital signs (systolic and diastolic blood pressure [SBP and DBP] and pulse).  
If indicated based on medical history and/or symptoms additional exams will be performed at 
the discretion of the investigator. 
Whenever possible, assessments for an individual participant should be performed by the 
same member of the study site staff throughout the study. 
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings made after signing informed consent which meet the definition 
of an Adverse Event must be recorded as an adverse event on the Adverse Event eCRF. 
Vital signs 
Vital signs including blood pressure and pulse measurements will be assessed as indicated 
in Table 8-1. Whenever possible, assessments should be performed by the same study site 
staff member throughout the study. After the participant has been sitting for five minutes, with 
back supported and both feet placed on the floor, systolic and diastolic blood pressure will be 
measured three times using an automated validated device, e.g., OMRON devices, with an 
appropriately sized cuff. The repeat sitting measurements will be made at 1-2 minute 
intervals and the mean of the three measurements will be used. In case the cuff sizes 
available are not large enough for the participant's arm circumference, a sphygmomanometer 
with an appropriately sized cuff may be used. Measurements will be recorded in the source 
documentation and the average of the two measurements will be entered on the Vital Signs 
CRF. 


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Assessment 
Specification 
Weight 
Body weight (to the nearest 0.1 kilogram (kg) in indoor clothing, but without shoes) will be 
measured as specified in Table 8-1. If possible, body weight assessments should be 
performed by the same study site staff member and using the same scale throughout the 
study. 
8.5.1 
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens listed below, unless noted 
otherwise. Details on the collections, shipment of samples and reporting of results by the central 
laboratory are provided to investigators in the laboratory manual. Refer to the Laboratory 
Manual for identification of laboratory reference range values and the schema for notification 
of site staff and Novartis for out-of-range values. 
As per Section 4.6, changes in safety assessments can be added as one of the risk mitigation 
procedure during public health emergency declared by local or regional authorities. 
If participants cannot visit the site for safety lab assessments conducted through central labs, 
local lab collection may be used during a Public Health emergency as declared by Local or 
Regional authorities i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site 
study visits. 
Clinically notable laboratory findings are defined in Section 16.1. 
Clinically significant abnormalities must be recorded as current medical conditions or adverse 
events as appropriate. 
All participants with laboratory tests containing clinically significant abnormal values are to be 
followed until the values return to normal ranges or until a valid reason, other than treatment 
related AE, is defined. 
Blood collection and safety assessments should be done prior to study treatment administration 
and should be taken as shown in Table 8-1. 
Table 8-3 
Test categories and names 
Test Category 
Test Name 
Hematology 
Hematocrit, hemoglobin, Ery. Mean Corpuscular Volume (MCV), Erythrocytes, Leucocytes, 
platelets, Erythrocyte Cell Morphology, differential (basophils, eosinophils, lymphocytes, 
monocytes, neutrophils, bands) 
Chemistry 
Albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) Serum Glutamic 
Pyruvic Transaminase (SGPT), aspartate aminotransferase (AST) ,Serum Glutamic 
Oxaloacetic Transaminase (SGOT) , gamma-glutamyl-transferase (GGT), bicarbonate, 
calcium, phosphate, sodium, potassium, creatinine, total bilirubin (TBL), total cholesterol, 
low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, total 
protein, triglycerides, urea, uric acid, amylase, lipase, hemoglobin A1c (HbA1c). 
Urinalysis 
Specific gravity, protein, glucose, pH, blood, urine blood dipstick (non-hemolyzed), urine 
blood dipstick (hemolyzed), bilirubin, ketones and white blood cells (WBCs). 
Coagulation 
Prothrombin time (PT), International normalized ratio [INR]), activated Partial 
Thromboplastin Time (aPTT). 
Additional tests 
24 hr UPCR 
 
First morning void (FMV) UPCR  
Pregnancy Test 
Serum / Urine pregnancy test (refer to 'Pregnancy and assessments of fertility' 
Section 8.5.3) 


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8.5.1.1 
Coagulation panel 
Coagulation panel will be evaluated locally for general safety and additional characterization 
of the disease. 
8.5.1.2 
Lipid Panel 
A lipid profile including High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), 
cholesterol and triglycerides will be measured from a fasting blood sample. 
8.5.1.3 
Urinary analysis 
There will be two types of urinary collection, both performed at participants' home: 
• 24-hour urine collection, corresponding to the 24-hour collection of the urine the days 
preceding specific visits, as outlined in Table 8-1. 
• First morning void (FMV) urine collection on the day of visits as specified in Table 8-1. 
8.5.1.3.1 Local urinalysis 
The participant's FMV urine sample will be used as outlined below. 
• local determination of urinary sediment: Presence of red blood cells (RBCs), white blood 
cells (WBCs), epithelial cells, and cellular casts will be determined by microscopic 
evaluation or automatic analyzer and recorded on the appropriate eCRF. Active urinary 
sediment is defined as the presence of cellular casts which are granular casts or red blood 
cells, or hematuria (>5 RBCs per high power field) , 
• central determination of UPCR, as outlined in Efficacy Section 8.4.4 
• Where required, FMV urine sample will be used for urine pregnancy tests. 
Material for the FMV urine collection will be dispensed at participant's previous visit. Please 
refer to the central laboratory manual for additional details.  
8.5.1.3.2 24-hour urine collection 
A 24-hour urine collection is done by collecting urine in a special container over a full 24-hour 
period. 
Instructions regarding the timing, the collection and the storage of the 24-hour urine collection 
will be detailed within the laboratory manual. 
This 24-hour urine collection will be used for central determination of the UPCR 
 
as mentioned in Section 8.4.4 and Section 8.4.5. 
8.5.2 
Electrocardiogram (ECG) 
Electrocardiograms (ECGs) will be locally collected and evaluated at Visit Week 
104E1. ECGs must be recorded after 10 minutes rest in the supine position to ensure a stable 
measurement. A single 12-lead ECG is collected. The Fridericia QT correction formula (QTcF) 
must be used for clinical decisions. The investigator must calculate QTcF if it is not auto-
calculated by the ECG machine. The original ECGs (on non-heat-sensitive paper or a certified 


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copy on non-heat-sensitive paper), appropriately signed, must be collected and archived at the 
study site. 
Interpretation of the tracing must be made by a qualified physician and documented on the 
appropriate CRF. Each ECG tracing should be labeled with the study number, participant 
initials (where regulations permit), participant number, date, and kept in the source documents 
at the study site. Clinically significant abnormalities should be reported on the appropriate CRF. 
Clinically significant findings must be discussed with Novartis prior to investigational 
treatment administration.  
The preferred sequence of cardiovascular data collection during study visits is ECG collection 
first, followed by vital signs, blood sampling, and any remaining assessments for that visit (refer 
to flow diagram below). 
Additional, unscheduled, safety ECGs may be repeated at the discretion of the investigator at 
any time during the study as clinically indicated. For any ECGs with participant safety concerns, 
two additional ECGs must be performed to confirm the safety finding. ECG safety monitoring, 
or a review process, should be in place for clinically significant ECG findings at Week 104E1 
before administration of study treatment and during the study. 
Clinically significant abnormalities must be recorded on the CRF as adverse events. 
Figure 8-1 
Timing of study procedures 
 
8.5.2.1 
Cardiac imaging - MRA (magnetic resonance angiography), MUGA 
(multiple gated acquisition) scan or echocardiogram 
Not Applicable 
8.5.2.2 
Cardiac enzymes 
Not Applicable 
8.5.3 
Pregnancy and assessments of fertility 
All pre-menopausal women who are not surgically sterile will have monthly local urine 
pregnancy testing as indicated in Table 8-1. Urine pregnancy kits would be provided to 
participants to perform the test at home and would report the result to site. A simple diary to 
record dates and outcome of home urinary test would be provided. Additional pregnancy testing 
might be performed if requested by local requirements. A serum β-hCG test will be performed 
only if there is positive urine dipstick test. A positive urine pregnancy test during the treatment 
periods of the study requires immediate interruption of study treatment until a serum β-subunit 
of human chorionic gonadotropin (β-hCG) is performed and found to be negative. If the serum 
β-hCG test is positive, the participant must be discontinued from the study treatment. 


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Secukinumab, MPA and corticosteroids should not be given to pregnant women; therefore, 
highly effective methods of birth control must be used for women of childbearing potential (see 
exclusion criteria definitions, Section 5.2). 
Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained as 
source documents. Subsequent hormone level assessment to confirm the woman is not of child-
bearing potential must also be available as source documentation in the following cases: 
1. Surgical bilateral oophorectomy without a hysterectomy 
2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile. 
8.5.4 
Appropriateness of safety measurements 
The safety assessments selected are standard for this indication/participant population. 
8.6 
Additional assessments 
No additional tests will be performed on participants entered into this study. 
9 
Discontinuation and completion 
9.1 
Discontinuation from study treatment and from study 
9.1.1 
Discontinuation from study treatment 
Discontinuation of study treatment for a participant occurs when study treatment is permanently 
stopped for any reason (prior to the planned completion of study drug administration, if any) 
and can be initiated by either the participant or the investigator. 
The investigator must discontinue study treatment for a given participant if, he/she believes that 
continuation would negatively impact the participant's well-being. 
Discontinuation from study treatment is required under the following circumstances: 
• Participant/guardian decision - Participants may choose to discontinue study treatment for 
any reason at any time 
• Pregnancy (see Section 10.1.4 Pregnancy reporting) 
• Participant received a live vaccine 
• Use of prohibited treatment as outlined in Section 6.2.2 prohibited medication 
• Any situation or protocol deviation in which study participation might result in a safety 
risk to the participant 
• Emergence of the following AEs:  
• Any AE that in the judgment of the investigator, taking into account the participant's 
overall status, prevents the participant from continuing study treatment (for example 
sepsis) 
• Any severe or serious AE that requires treatment with an unacceptable co-medication 
• Severe hypersensitivity reaction or anaphylactic reaction 


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• Any laboratory abnormalities that in the judgment of the investigator, taking into account 
the participant's overall status, prevents the participant from continuing study treatment 
• Unsatisfactory therapeutic effect 
If discontinuation from study treatment occurs, the investigator should make a reasonable effort 
to understand the primary reason for the participant’s discontinuation from study treatment and 
record this information in eCRF. 
Participants who discontinue from study treatment agree to return for the end of treatment and 
follow-up visits indicated in the Assessment Schedule (refer to Section 8). 
If the participant cannot or is unwilling to attend any visit(s), the site staff should maintain 
regular telephone contact with the participant, or with a person pre-designated by the 
participant. This telephone contact should preferably be done according to the study visit 
schedule. 
All participants who prematurely discontinue study treatment should perform the EOT study 
visit four weeks after their last study treatment administration. Adverse event monitoring should 
be continued for at least 84 days following the last dose of study treatment. 
An End of Study (EOS) visit is to be done 12 weeks after last study treatment administration 
for all participants, regardless of whether they complete the entire study as planned or 
discontinue prematurely. 
The investigator must also contact the IRT to register the participant’s discontinuation from 
study treatment. 
9.1.2 
Discontinuation from study 
Discontinuation from study is when the participant permanently stops receiving the study 
treatment, and further protocol-required assessments or follow-up, for any reason. 
If the participant agrees, a final evaluation at the time of the participant’s study discontinuation 
should be made as detailed in the assessment table (refer to Section 8). 
9.1.3 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits without 
stating an intention to discontinue from study treatment or discontinue from study or withdraw 
consent/oppose to the use of their data/biological samples, the investigator must show "due 
diligence" by documenting in the source documents steps taken to contact the participant, e.g., 
dates of telephone calls, registered letters, etc. A participant should not be considered as lost to 
follow-up until due diligence has been completed. 
9.2 
Withdrawal of informed consent/Opposition to use 
data/biological samples 
Withdrawal of consent/opposition to use data/biological samples occurs when a participant: 
• Explicitly requests to stop use of their biological samples and/or data (opposition to use 
participant’s data and biological samples) 


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and 
• No longer wishes to receive study treatment 
and 
• Does not want any further visits or assessments (including further study-related contacts) 
This request should be in writing (depending on local regulations) and recorded in the source 
documentation. 
In this situation, the investigator should make a reasonable effort (e.g., telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw their 
consent/opposition to use data/biological samples and record this information. 
Where consent to the use of Personal and Coded Data is not required in a certain country's legal 
framework, the participant therefore cannot withdraw consent. However, they still retain the 
right to object to the further collection or use of their Personal Data. 
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up. 
If the participant agrees, a final evaluation at the time of the participant’s withdrawal of 
consent/opposition to use data/biological samples should be made as detailed in the assessment 
table (refer to Section 8). 
Further details on withdrawal of consent or the exercise of participants' data privacy rights are 
included in the corresponding informed consent form.  
9.3 
Study completion and post-study treatment 
Study completion is defined as when the last participant finishes their Study Completion visit 
and any repeat assessments associated with this visit have been documented and followed-up 
appropriately by the Investigator or, in the event of an early study termination decision, the date 
of that decision. 
A participant will be considered to have completed the study when she/he has completed the 
last planned visit in the protocol. 
The investigator must provide follow-up medical care for all participants, including participants 
who are prematurely withdrawn from the study, or must refer them for appropriate ongoing 
care. This care may include initiating another treatment outside of the study, as deemed 
appropriate by the investigator. 
All enrolled and/or treated participants should have a safety follow-up call conducted 84 days 
after last administration of study treatment. The information collected is kept as source 
documentation. All SAEs reported during this time period must be reported as described in 
Section 10.1.3 SAE reporting. Documentation of attempts to contact the participant should be 
recorded in the source documentation. 


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9.4 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time. This may include reasons related to the 
benefit/risk assessment of participating in the study (e.g., outcome of planned core study 
CAIN457Q12301 futility analysis), practical reasons (including slow enrollment), or for 
regulatory or medical reasons. 
In taking the decision to terminate, Novartis will always consider participant welfare and safety. 
Should early termination be necessary, participants must be seen as soon as possible and treated 
as a prematurely withdrawn participant. The investigator may be informed of additional 
procedures to be followed in order to ensure that adequate consideration is given to the 
protection of the participant’s interests. The investigator or sponsor depending on local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
10 
Safety monitoring, reporting and committees 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical 
investigation participant after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. 
The investigator has the responsibility for managing the safety of individual participant and 
identifying adverse events. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, 
accompanied by the following information (as far as possible) (if the event is serious refer to 
Section 10.1.2): 
1. The severity grade 
• mild: usually transient in nature and generally not interfering with normal activities 
• moderate: sufficiently discomforting to interfere with normal activities 
• severe: prevents normal activities 
2. Its relationship to the study treatment and other investigational treatment. If the event is 
due to lack of efficacy or progression of underlying illness (i.e., progression of the study 
indication) the assessment of causality will usually be ‘Not suspected’. The rationale for 
this guidance is that the symptoms of a lack of efficacy or progression of underlying 
illness are not caused by the trial drug, they happen in spite of its administration and/or 
both lack of efficacy and progression of underlying disease can only be evaluated 
meaningfully by an analysis of cohorts, not on a single participant 
3. Its duration (start and end dates or ongoing) and the outcome must be reported 


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4. Whether it constitutes a SAE (see Section 10.1.2 for definition of SAE) and which 
seriousness criteria have been met 
5. Action taken regarding with study treatment. 
All adverse events must be treated appropriately. Treatment may include one or more of the 
following: 
• Dose not changed 
• Dose Reduced/increased 
• Drug interrupted/permanently discontinued 
6. Its outcome (not recovered/not resolved; recovered/resolved; recovered/resolved with 
sequelae; fatal; or unknown) 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued for at least 84 days following the last dose of 
study treatment. 
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be permanent (e.g., continuing at the end of the study), and assessment must be made at each 
visit (or more frequently, if necessary) of any changes in severity, the suspected relationship to 
the interventions required to treat it, and the outcome. 
Information about adverse drug reactions for the investigational drug can be found in the 
Investigator's Brochure (IB). 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values which are considered to be non-typical in participant 
with the underlying disease. Alert ranges for laboratory and other test abnormalities are included 
in Section 16.1. 
10.1.2 
Serious adverse events 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following 
criteria: 
• fatal 
• life-threatening 
Life-threatening in the context of a SAE refers to a reaction in which the participant was at risk 
of death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (refer to the ICH E2D 2003 Guidelines). 


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• results in persistent or significant disability/incapacity  
• constitutes a congenital anomaly/birth defect 
• requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:  
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
• social reasons and respite care in the absence of any deterioration in the participant’s 
general condition 
• treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g., defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant”. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that 
do not result in hospitalization or development of dependency or abuse (refer to the 
ICH E2D 2003 Guidelines). 
All new malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met and the malignant neoplasm is not a disease progression of the 
study indication. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the product are also considered serious adverse 
event irrespective if a clinical event has occurred. 
10.1.3 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent and until 12 weeks (84 days) following the last administration 
of study treatment, or 30 days after the participant has stopped study participation (whichever 
is later) must be reported to Novartis safety immediately, without undue delay, but under no 
circumstances later than within 24 hours of obtaining knowledge of the events (Note: If more 
stringent, local regulations regarding reporting timelines prevail). Detailed instructions 
regarding the submission process and requirements are to be found in the investigator folder 
provided to each site. Information about all SAEs is collected and recorded on the eSAE with 
paper backup. Serious Adverse Event Report Form; all applicable sections of the form must be 
completed in order to provide a clinically thorough report. 


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All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
immediately, without undue delay, but under no circumstances later than within 24 hours of the 
investigator receiving the follow-up information (Note: If more stringent, local regulations 
regarding reporting timelines prevail). An SAE occurring at a different time interval or 
otherwise considered completely unrelated to a previously reported one must be reported 
separately as a new event. 
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the study treatment, a Novartis Chief Medical Office 
and Patient Safety (CMO&PS) Department associate may urgently require further information 
from the investigator for health authority reporting. Novartis may need to issue an Investigator 
Notification (IN) to inform all investigators involved in any study with the same study treatment 
that this SAE has been reported. 
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with the European 
Union (EU) Guidance 2011/C 172/01 or as per national regulatory requirements in participating 
countries. 
Any SAEs experienced after the 84 days following the last administration of study 
treatment/should only be reported to Novartis Safety if the investigator suspects a causal 
relationship to study treatment, unless otherwise specified by local law/regulations. 
10.1.4 
Pregnancy reporting 
Pregnancies 
If a female trial participant becomes pregnant, the study treatment should be stopped, and the 
pregnancy consent form should be presented to the trial participant. The participant must be 
given adequate time to read, review and sign the pregnancy consent form. This consent form is 
necessary to allow the investigator to collect and report information regarding the pregnancy. 
To ensure participant safety, each pregnancy occurring after signing the informed consent must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. 
Pregnancy should be recorded and reported by the investigator to the CMO&PS. Pregnancy 
follow-up should be recorded on the same form and should include an assessment of the 
possible relationship to the study treatment any pregnancy outcome. Any SAE experienced 
during pregnancy must be reported. After consent is provided, the pregnancy reporting will 
occur up to one year after the estimated date of delivery. 
10.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition). 


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Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate CRF irrespective of whether or not associated with an AE/SAE and reported to 
Safety only if associated with an SAE. Misuse or abuse will be collected and reported in the 
safety database irrespective of it being associated with an AE/SAE within 24 hours of 
Investigator’s awareness. 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in Dosing 
CRF (Yes/No) 
Document in AE eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated with an 
AE 
Only if associated with an 
SAE 
Misuse/Abuse 
Yes 
Yes 
Yes, even if not 
associated with a SAE 
For more information on AE and SAE definition and reporting requirements, please see the 
respective sections. 
10.2 
Additional Safety Monitoring 
10.2.1 
Liver safety monitoring 
To ensure participant safety and enhance reliability in determining the hepatotoxic potential of 
an investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed. 
Please refer to Table 16-2 in Section 16.2 for complete definitions of liver laboratory triggers. 
Once a participant is exposed to study treatment, every liver event defined in Table 16-3 should 
be followed up by the investigator or designated personnel at the trial site, as summarized 
below. Additional details on actions required in case of liver events are outlined in Table 16-2. 
Repeat liver chemistry tests (i.e. ALT, AST, total bilirubin (TBL), PT/INR, ALP and GGT) to 
confirm elevation. 
• These liver chemistry repeats will be performed using the central laboratory. If results will 
not be available from the central laboratory, then the repeats can also be performed at a 
local laboratory to monitor the safety of the participant. If a liver event is subsequently 
reported, any local liver chemistry tests previously conducted that are associated with this 
event should have results recorded on the appropriate CRF. 
• If the initial elevation is confirmed, close observation of the participant will be initiated, 
including consideration of treatment interruption if deemed appropriate. 
• Discontinuation of the investigational drug (refer to the Section 9.1.1 Discontinuation of 
study treatment), if appropriate. 
• Hospitalization of the participant, if appropriate. 


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• Causality assessment of the liver event. 
• Thorough follow-up of the liver event should include investigations based on 
investigator’s discretion: serology tests, imaging and pathology assessments, 
hepatologist’s consultancy; obtaining more detailed history of symptoms and prior or 
concurrent diseases, history of concomitant drug use, exclusion of underlying liver disease 
All follow-up information and procedures performed must be recorded as appropriate in the 
CRF. 
10.3 
Committees 
10.3.1 
Data Monitoring Committee 
This study will include a Data Monitoring Committee (DMC) which will function 
independently of all other individuals associated with the conduct of this clinical trial, including 
the site investigators participating in the study. The DMC will assess at defined intervals the 
progress of a clinical trial, safety data, and critical efficacy variables and recommend to the 
sponsor whether to continue, modify, or terminate a trial. 
Specific details regarding composition, responsibilities, data monitoring, and meeting 
frequency, and documentation of DMC reports, minutes, and recommendations will be 
described in a separate charter that is established between the sponsor and the DMC. 
10.3.2 
Steering Committee 
The Steering Committee (SC) will be established comprising investigators participating in the 
trial, i.e., not being members of the DMC and Novartis representatives from the Clinical Trial 
Team. 
The SC will ensure transparent management of the study according to the protocol through 
recommending and approving modifications as circumstances require. The SC will review 
protocol amendments as appropriate. Together with the clinical trial team, the SC will also 
develop recommendations for publications of study results including authorship rules. The 
details of the role of the steering committee will be defined in the steering committee charter. 
11 
Data Collection and Database management 
11.1 
Data collection 
Designated investigator staff will enter the data required by the protocol into the eCRFs. The 
eCRFs have been built using fully validated secure web-enabled software that conforms to the 
Code of Federal Regulation (CFR) 21 CFR Part 11 requirements. Investigator site staff will not 
be given access to the Electronic Data Capture (EDC) system until they have been trained. 
Automatic validation programs check for data discrepancies in the eCRFs, allow modification 
and/or verification of the entered data by the investigator staff. 
The investigator/designee is responsible for assuring that the data (recorded on CRFs) (entered 
into eCRF) is complete, accurate, and that entry and updates are performed in a timely manner. 
The Investigator must certify that the data entered are complete and accurate. 


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After final database lock, the investigator will receive copies of the participant data for 
archiving at the investigational site. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
11.2 
Database management and quality control 
Novartis personnel (or designated Clinical Research Organization (CRO) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated investigator 
site staff are required to respond promptly to queries and to make any necessary changes to the 
data. 
Concomitant treatments and prior medications entered into the database will be coded using the 
WHO Drug Reference List, which employs the Anatomical Therapeutic Chemical classification 
system. Medical history/current medical conditions and adverse events will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA) terminology. 
Dates of enrollment and study completion, as well as data about all study treatment dispensed 
to the participant and all dosage regimen changes, will be tracked using an IRT. The system 
will be supplied by a vendor, who will also manage the database. The data will be sent 
electronically to Novartis (or a designated CRO) at specific timelines. 
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked. Any changes to the database after that time can only 
be made after written agreement by Novartis development management. 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements (eCRFs) with the 
investigators and their staff. During the study, Novartis employs several methods of ensuring 
protocol and GCP compliance and the quality/integrity of the sites’ data. The field monitor will 
visit the site to check the completeness of participant records, the accuracy of data capture / data 
entry, the adherence to the protocol and to Good Clinical Practice, the progress of enrollment, 
and to ensure that study treatment is being stored, dispensed, and accounted for according to 
specifications. Key study personnel must be available to assist the field monitor during these 
visits. Continuous remote monitoring of each site’s data may be performed by a centralized 
Novartis Clinical Research Associate (CRA) organization. Additionally, a central analytics 
organization may analyze data & identify risks & trends for site operational parameters, and 
provide reports to Novartis clinical teams to assist with trial oversight. 
The investigator must maintain source documents for each participant in the study, consisting 
of case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
participant's file. The investigator must also keep the original informed consent form signed by 
the participant (a signed copy is given to the participant). 


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The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
participants will be disclosed. 
12 
Data analysis and statistical methods 
Any data analysis carried out independently by the investigator should be submitted to Novartis 
before publication or presentation. 
12.1 
Analysis sets 
The Full Analysis Set (FAS) will be comprised of all analyzable subjects from the FAS of core 
study to whom study treatment has been assigned. Subjects will be analyzed according to the 
study treatment received. 
The Safety Set includes all subjects who received at least one dose of study treatment. Subjects 
will be analyzed according to the study treatment received. 
12.2 
Participant demographics and other Baseline characteristics 
Demographic and other Baseline data including disease characteristics will be summarized 
descriptively by core study treatment groups in FAS. 
Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
standard deviation, median, minimum, and maximum will be presented. . 
Relevant medical histories and current medical conditions at Baseline will be summarized by 
system organ class and preferred term, by core study treatment group. 
12.3 
Treatments 
The analysis of study treatment data will be based on the safety set. The number of active 
injections received will be presented by core study treatment group. The duration of exposure 
to study treatment will also be summarized by core study treatment group. In addition, the 
number and percentage of subjects with cumulative exposure levels (e.g., any exposure, ≥ 1 
week, ≥ 2 weeks, ≥ 3 weeks, ≥ 4 weeks, ≥ 8 weeks, etc.) will be presented. 
12.4 
Analysis supporting primary objectives 
The primary endpoint CRR at Week 260 will be summarized using descriptive statistics 
including proportion of responders with 95% confidence interval. 
12.4.1 
Definition of primary endpoint(s) 
Primary endpoint for this study is CRR at Week 260. 
CRR is defined as: 


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• eGFR is within the normal range or no less than 85% of Baseline, 
and 
• 24-hour UPCR ≤ 0.5 mg/mg. 
12.4.2 
Statistical model, hypothesis, and method of analysis 
No formal statistical testing will be applied for the primary variable. 
The primary variable will be summarized by treatment group in FAS, using descriptive statistics 
and 95% confidence interval for proportion of responders. 
12.4.3 
Handling of intercurrent events of primary estimand 
Composite strategy (non-responder imputation) will be used for treatment discontinuation and 
rescue treatment. 
12.4.4 
Handling of missing values not related to intercurrent event 
Non responder imputation will be used for missing data in primary estimand analysis. Data will 
also be analyzed descriptively as observed. 
12.4.5 
Sensitivity analyses 
Sensitivity analyses may be specified in statistical analysis plan. 
12.4.6 
Supplementary analysis 
Supplementary analyses may be specified in statistical analysis plan. 
12.5 
Analysis supporting secondary objectives 
Not applicable 


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12.7 
Interim analyses 
Interim analyses may be performed for purposes of publication and/or to support health 
authority interactions, as necessary. 
12.8 
Sample size calculation 
Not applicable. Sample size is based on participants continuing from core study to extension 
study. 
12.8.1 
Primary endpoint(s) 
Not applicable. 
13 
Ethical considerations and administrative procedures 
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations (including European Directive 2001/20/EC, US CFR 21), and with the ethical 
principles laid down in the Declaration of Helsinki. 


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13.2 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written informed consent form, consent form updates, participant recruitment procedures (e.g., 
advertisements) and any other written information to be provided to participants. Prior to study 
start, the investigator is required to sign a protocol signature page confirming his/her agreement 
to conduct the study in accordance with these documents and all of the instructions and 
procedures found in this protocol and to give access to all relevant data and records to Novartis 
monitors, auditors, Novartis Quality Assurance representatives, designated agents of Novartis, 
IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site is 
requested by a regulatory authority, the investigator must inform Novartis immediately that this 
request has been made. 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in EudraCT. In addition, after study completion (defined as last patient last visit) 
and finalization of the study report the results of this trial will be submitted for publication and 
posted in a publicly accessible database of clinical trial results, such as the Novartis clinical trial 
results website and all required Health Authority websites (e.g., Clinicaltrials.gov, EudraCT 
etc.) . 
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial investigator 
meetings. 
13.4 
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management System (QMS) that includes all activities 
involved in quality assurance and quality control, to ensure compliance with written Standard 
Operating Procedures as well as applicable global/local GCP regulations and ICH Guidelines. 
Audits of investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of the 
clinical trial. The clinical audit process uses a knowledge/risk based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal standard operating procedures (SOPs), and are performed according to 
written Novartis processes. 
13.5 
Participant Engagement 
The following participant engagement initiatives are included in this study and will be provided, 
as available, for distribution to study participants 
• Thank You letter 
• Plain language trial summary - after clinical study report (CSR) publication 


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14 
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of participants should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and Health Authorities, where required, it cannot be 
implemented. 
14.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for participant safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations. 


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15 
References 
References are available upon request 
Allam R, Anders HJ (2008) The role of innate immunity in autoimmune tissue injury. Curr 
Opin Rheumatol p. 538-44. 
Anon (2001) Recommendations for the prevention and treatment of glucocorticoid-induced 
osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on 
Glucocorticoid-Induced Osteoporosis. Arthritis Rheum; 44(7):1496-503 
Anon (2015). Committee for Medicinal Products for Human Use (CHMP) (2015) guidance 
document: https://www.ema.europa.eu/documents/scientific-guideline/guideline-clinical-
investigation-medicinal-products-treatment-systemic-lupus-erythematosus-lupus_en.pdf 
(Accessed 02 Dec 2021).. 
Appel GB, Contreras G, Dooley MA, et al (2009) Mycophenolate mofetil versus 
cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol p. 1103-12. 
Bertsias GK, Tektonidou M, Amoura Z, et al (2012) Joint European League Against 
Rheumatism and European Renal Association-European Dialysis and Transplant Association 
(EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus 
nephritis. Ann Rheum Dis p. 1771-82. 
Cervera R, Khamashta MA, Font J, et al (2003) Morbidity and mortality in systemic lupus 
erythematosus during a 10-year period: a comparison of early and late manifestations in a 
cohort of 1,000 patients. Medicine (Baltimore) p. 299-308. 
Chilton F, Collett RA (2008) Treatment choices, preferences and decision-making by patients 
with rheumatoid arthritis. Musculoskeletal Care p. 1-14. 
Costa R, Antunes P, Salvador P, et al (2021) Secukinumab on Refractory Lupus Nephritis. 
Cureus; 13(8): e17198 
Crispín JC, Oukka M, Bayliss G, et al (2008) Expanded double negative T cells in patients 
with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol p. 
8761-6. 
Faurschou M, Dreyer L, Kamper AL, et al (2010) Long-term mortality and renal outcome in a 
cohort of 100 patients with lupus nephritis. Arthritis Care Res (Hoboken) p. 873-80. 
Feldman CH, Hiraki LT, Winkelmayer WC, et al (2015) Serious infections among adult 
Medicaid beneficiaries with systemic lupus erythematosus and lupus nephritis. Arthritis 
Rheumatol p. 1577-85. 
Furie R, Rovin BH, Houssiau F, et al (2020) Two-Year, Randomized, Controlled Trial of 
Belimumab in Lupus Nephritis. N Engl J Med p. 1117-1128. 
Grootscholten C, Berden JH (2006) Discontinuation of immunosuppression in proliferative 
lupus nephritis: is it possible? Nephrol Dial Transplant p. 1465-9. 


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Hahn BH, McMahon M, Wilkinson A, et al (2012) American College of Rheumatology 
guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 
(Hoboken) p. 797-808. 
Hamm R, Patel B, Whittlestone T, et al (2000) Patient self-injection: a new approach to 
administering luteinizing hormone-releasing hormone analogues. BJU International; 86: 840-
2 
ICH E2D (2003) Clinical Safety Data Management: Definitions and Standards for expedited 
reporting. Accessed from: https://www.ema.europa.eu/en/ich-e2d-post-approval-safety-data-
management (Accessed 02 Dec 2021). 
Kivitz A, Cohen S, Dowd JE, et al (2006) Clinical assessment of pain, tolerability, and 
preference of an autoinjection pen versus a prefilled syringe for patient self-administration of 
the fully human, monoclonal antibody adalimumab: the TOUCH trial. Clin Ther p. 1619-29. 
Krebs CF, Schmidt T, Riedel JH, et al (2017) T helper type 17 cells in immune-mediated 
glomerular disease. Nat Rev Nephrol p. 647-659. 
Levey AS, Stevens LA, Schmid CH, et al (2009) A new equation to estimate glomerular 
filtration rate. Ann Intern Med p. 604-12. 
Markowitz GS, D'Agati VD (2007) The ISN/RPS 2003 classification of lupus nephritis: an 
assessment at 3 years. Kidney Int p. 491-5. 
Martínez-Martínez MU, Mandeville P, Llamazares-Azuara L, et al (2013) CKD-EPI is the 
most reliable equation to estimate renal function in patients with systemic lupus 
erythematosus. 
Nowling TK, Gilkeson GS (2011) Mechanisms of tissue injury in lupus nephritis. Arthritis 
Res Ther p. 250. 
Palmer SC, Tunnicliffe DJ, Singh-Grewal D, et al (2017) Induction and Maintenance 
Immunosuppression Treatment of Proliferative Lupus Nephritis: A Network Meta-analysis 
of Randomized Trials. Am J Kidney Dis p. 324-336. 
Rovin BH, Parikh SV (2014) Lupus nephritis: the evolving role of novel therapeutics. Am J 
Kidney Dis p. 677-90. 
Rovin BH, Teng YKO, Ginzler EM, et al (2021) Efficacy and safety of voclosporin versus 
placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-
controlled, phase 3 trial. Lancet p. 2070-2080. 
Satoh Y, Nakano K, Yoshinari H, et al (2018) A case of refractory lupus nephritis 
complicated by psoriasis vulgaris that was controlled with secukinumab. Lupus p. 1202-1206. 
Schwartz N, Goilav B, Putterman C (2014) The pathogenesis, diagnosis and treatment of 
lupus nephritis. Curr Opin Rheumatol p. 502-9. 
Tektonidou MG, Dasgupta A, Ward MM (2016) Risk of End-Stage Renal Disease in Patients 
With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis. 
Arthritis Rheumatol p. 1432-41. 


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Waldman M, Madaio MP (2005) Pathogenic autoantibodies in lupus nephritis. Lupus p. 19-
24. 
Wang H, Ren YL, Chang J, et al (2018) A Systematic Review and Meta-analysis of 
Prevalence of Biopsy-Proven Lupus Nephritis. Arch Rheumatol p. 17-25. 
Weening JJ, D'Agati VD, Schwartz MM, et al (2004) The classification of glomerulonephritis 
in systemic lupus erythematosus revisited. Kidney Int p. 521-30. 
Yu F, Haas M, Glassock R, et al (2017) Redefining lupus nephritis: clinical implications of 
pathophysiologic subtypes. Nat Rev Nephrol p. 483-495. 
Zhang Z, Kyttaris VC, Tsokos GC (2009) The role of IL-23/IL-17 axis in lupus nephritis. J 
Immunol p. 3160-9. 
Zickert A, Amoudruz P, Sundström Y, et al (2015) IL-17 and IL-23 in lupus nephritis - 
association to histopathology and response to treatment. BMC Immunol p. 7. 


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16 
Appendices 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs 
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. Clinically notable values will be forwarded to Novartis at the same time that 
they are sent to investigators. Any action based on these laboratory values should be discussed 
with Novartis personnel. 
Table 16-1 
Safety Analyses: Expanded limits and Notable Criteria 
Laboratory variable 
Notable Criteria 
Standard Units 
SI units 
LIVER FUNCTION VARIABLE 
  
  
SGOT (AST) 
>3 x ULN 
> 3 x ULN 
SGPT (ALT) 
>3 x ULN 
> 3 x ULN 
Bilirubin 
> 2 x ULN 
> 2 x ULN 
Alkaline Phosphatase 
> 2.5 x ULN 
> 2.5 x ULN 
HEMATOLOGY VARIABLE 
  
  
Hemoglobin: 20 g/L decrease from Baseline 
  
  
Platelet count: < 50 x 10 E9/L 
  
  
White Blood Cell Count: < 0.8 x LLN 
  
  
Neutrophil: < 0.9 x LLN 
  
  
16.2 
Appendix 2: Liver event and laboratory trigger definitions & 
follow-up requirements 
Table 16-2 
Liver event and laboratory trigger definitions 
  
Definition/ threshold 
Liver laboratory triggers 
If ALT, AST and total 
bilirubin normal at 
Baseline: 
● 3 × ULN <ALT/AST ≤ 5×ULN 
● 1.5 × ULN < TBL × ULN 
● ALT or AST > 5 × ULN 
● ALP > 2 × ULN (in the absence of known bone pathology) 
● Total bilirubin > 3 × ULN (in the absence of known Gilbert syndrome) 
● ALT or AST > 3 × ULN and INR > 1.5 
● Potential Hy’s Law cases (defined as ALT or AST > 3 × ULN and Total bilirubin > 
2 × ULN [mainly conjugated fraction] without notable increase in ALP to > 2 × 
ULN) 
● Any clinical event of jaundice (or equivalent term) 
● ALT or AST > 3 × ULN accompanied by (general) malaise, fatigue, abdominal 
pain, nausea, or vomiting, or rash with eosinophilia 
● Any adverse event potentially indicative of a liver toxicity* 
*These events cover the following: Hepatic failure, fibrosis and cirrhosis, and other 
liver damage-related conditions; the non-infectious hepatitis; the benign, malignant 
and unspecified liver neoplasms TBL: total bilirubin; ULN: upper limit of normal 
If ALT or AST abnormal 
at Baseline: 
● ALT or AST > 3x Baseline or > 300 U/L (whichever occurs first) 


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Table 16-3 
Follow up requirements for liver laboratory triggers 
Criteria 
Actions required 
Follow-up monitoring 
Potential Hy’s Law 
casea 
1. Discontinue the study treatment immediately 
2. Hospitalize, if clinically appropriate 
3. Establish causality 
4. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion) 
AST or ALT 
  
  
> 8 × ULN 
1. Discontinue the study treatment immediately 
2. Hospitalize if clinically appropriate 
3. Establish causality 
4. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion) 
> 3 × ULN and INR > 
1.5 
1. Discontinue the study treatment immediately 
2. Hospitalize, if clinically appropriate 
3. Establish causality 
4. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion) 
> 5 to ≤ 8 × ULN 
1. Repeat Liver function test (LFT) within 48 hours 
2. If elevation persists, continue follow-up monitoring 
3. If elevation persists for more than 2 weeks, 
discontinue the study drug 
4. Establish causality 
5. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion) 
> 3 × ULN 
accompanied by 
symptomsb 
1. Discontinue the study treatment immediately 
2. Hospitalize if clinically appropriate 
3. Establish causality 
4. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion) 
> 3 to ≤ 5 × ULN 
(participant is 
asymptomatic) 
1. Repeat LFT within the next week 
2. If elevation is confirmed, initiate close observation 
of the participant 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks 
ALP (isolated) 
  
  
> 2 × ULN (in the 
absence of known 
bone pathology) 
1. Repeat LFT within 48 hours 
2. If elevation persists, establish causality 
3. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
TBL (isolated) 
  
  
> 2 × ULN (in the 
absence of known 
Gilbert syndrome) 
1. Repeat LFT within 48 hours 
2. If elevation persists, discontinue the study drug 
immediately 
3. Hospitalize if clinically appropriate 
4. Establish causality 
5. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion) 
Test for hemolysis (e.g., 
reticulocytes, haptoglobin, 
unconjugated [indirect] 
bilirubin) 
> 1.5 to ≤ 2 × ULN 
(participant is 
asymptomatic) 
1. Repeat LFT within the next week 
2. If elevation is confirmed, initiate close observation 
of the participant 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
Jaundice 
1. Discontinue the study treatment immediately 
2. Hospitalize the participant 
3. Establish causality 
4. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion) 


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Criteria 
Actions required 
Follow-up monitoring 
Any AE potentially 
indicative of a liver 
toxicity* 
1. Consider study treatment interruption or 
discontinuation 
2. Hospitalization if clinically appropriate 
3. Establish causality 
4. Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF 
Investigator discretion 
aElevated ALT/AST > 3 × ULN and TBL > 2 × ULN but without notable increase in ALP to > 2 × ULN 
b(General) malaise, fatigue, abdominal pain, nausea, or vomiting, or rash with eosinophilia cResolution 
is defined as an outcome of one of the following: (1) return to Baseline values, (2) stable values at 
three subsequent monitoring visits at least 2 weeks apart, (3) remain at elevated level after a 
maximum of 6 months, (4) liver transplantation, and (5) death. 
Based on investigator’s discretion investigation(s) for contributing factors for the liver event 
can include: Serology tests, imaging and pathology assessments, hepatologist’s consultancy; 
obtaining more detailed history of symptoms and prior or concurrent diseases, history of 
concomitant drug use, exclusion of underlying liver disease. 
16.3 
Appendix 3: Estimation of eGFR by the CKD-EPI 
The CKD-EPI creatinine equation uses a 2-slope spline to model the relationship between 
estimated GFR and serum creatinine, and a different relationship for age, sex and race. The 
equation was reported to perform better and with less bias than the MDRD Study equation, 
especially in patients with higher GFR. This results in reduced misclassification of CKD 
Levey et al 2009. 
  

SAP_001.pdf: 
Clinical Development 
AIN457/Secukinumab/Cosentyx® 
CAIN457Q12301E1 / NCT05232864   
A three-year, open-label extension study of subcutaneous 
secukinumab to evaluate the long-term efficacy, safety and 
tolerability in patients with active lupus nephritis  
Statistical Analysis Plan (SAP) Amendment 1 
Author: 
 
, 
, Trial Statisticians 
Document type: 
SAP Documentation 
Document status: 
Final 
Release date: 
04-Oct-2023
Number of pages: 
21 
Property of Novartis 
 Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 
Template Version 4.0, Effective from 23-Apr-2021 


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SAP Amendment 1 
 
Study No. CAIN457Q12301E1 
 
 
 
Document History – Changes compared to previous final version of SAP 
 
Date 
Time 
point 
Reason for 
update 
Outcome for 
update 
Section 
and title 
impacted 
(Current) 
 2-
Oct-
2023 
Prior 
to the 
final 
DBL 
of the 
study 
The 
purpose 
of 
this 
amendment is 
to update the 
analysis plan 
due 
to 
the 
early 
termination of 
the study 
Various changes to reflect the updated 
analysis due to early termination. 
Entire 
Document 


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SAP Amendment 1 
 
Study No. CAIN457Q12301E1 
 
 
 
Table of contents 
List of tables ........................................................................................................................ 4 
List of figures ...................................................................................................................... 4 
List of abbreviations ............................................................................................................ 5 
1 
Introduction ......................................................................................................................... 7 
1.1 
Study design ............................................................................................................ 7 
1.2 
Study objectives, endpoints and estimands ............................................................. 8 
1.2.1 
Primary estimand(s) ................................................................................ 9 
2 
Statistical methods ............................................................................................................. 10 
2.1 
Data analysis general information ......................................................................... 10 
2.2 
Analysis sets .......................................................................................................... 10 
2.3 
Patient disposition, demographics and other baseline characteristics ................... 10 
2.3.1 
Patient disposition ................................................................................. 10 
2.3.2 
Demographics and other baseline characteristics ................................. 11 
2.4 
Treatments (study treatment, rescue medication, concomitant therapies, 
compliance)............................................................................................................ 11 
2.4.1 
Study treatment / compliance ................................................................ 11 
2.4.2 
Concomitant medications ...................................................................... 12 
2.5 
Analysis supporting primary objective(s) .............................................................. 12 
2.5.1 
Primary endpoint(s) ............................................................................... 12 
2.5.2 
Statistical hypothesis, model, and method of analysis .......................... 12 
2.5.3 
Handling of missing values not related to intercurrent event ............... 12 
2.5.4 
Sensitivity analyses ............................................................................... 12 
2.6 
Analysis supporting secondary objectives ............................................................. 12 
2.7 
Safety analyses....................................................................................................... 12 
2.7.1 
Adverse events (AEs) ............................................................................ 12 
Algorithms for date imputations will be provided in Programming Datasets 
Specifications. ....................................................................................... 13 
2.7.2 
Laboratory data ..................................................................................... 13 
2.7.3 
Other safety data ................................................................................... 15 
2.8 
Pharmacokinetic endpoints .................................................................................... 16 
2.9 
PD and PK/PD analyses ........................................................................................ 16 
2.10 
Patient-reported outcomes ..................................................................................... 16 
2.11 
Biomarkers ............................................................................................................. 16 
 
 16 
2.13 
Interim analysis ...................................................................................................... 16 


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SAP Amendment 1 
 
Study No. CAIN457Q12301E1 
 
 
 
3 
Sample size calculation ..................................................................................................... 16 
4 
Change to protocol specified analyses .............................................................................. 17 
5 
Appendix ........................................................................................................................... 17 
5.1 
Description of efficacy variables ........................................................................... 17 
5.2 
Visit windows, baseline and post-baseline definitions, missing data handling ..... 18 
5.3 
Statistical models ................................................................................................... 19 
5.3.1 
Summary statistics for binary and categorical data ............................... 19 
5.3.2 
Crude incidence and related risk estimates ........................................... 20 
5.3.3 
Exposure adjusted incidence rate and related risk estimates ......... Error! 
Bookmark not defined. 
6 
Reference ........................................................................................................................... 20 
 
List of tables 
Table 1-1 
Objectives and related endpoints ............................................................ 8 
 
 13 
Table 2-2 
CTCAE grades for laboratory parameters to be analyzed .................... 14 
Table 2-3 
Liver-related events ............................................................................... 15 
Table 2-4 
Criteria for notable vital sign abnormalities .......................................... 16 
Table 5-1 
Analysis visit windows ......................................................................... 19 
 
List of figures 
Figure 1-1 
Study design ............................................................................................ 8 
 


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List of abbreviations 
AE 
ALP 
ALT 
AST 
ATC 
CKD 
CM 
CRF 
CRR 
CSR 
Adverse Event 
alkaline phosphatase 
alanine aminotransferase 
aspartate aminotransferase 
Anatomical Therapeutic Classification 
chronic kidney disease 
Concomitant Medication 
Case Report Form 
Complete Renal Response 
Clinical Study Re port 
CTCAE 
ECG 
eGFR 
ESRD 
FAS 
Common Criteria for Adverse Events 
Electrocardiogram 
estimated glomerular filtration rate 
end-stage renal disease 
Full Analysis Set 
GGT 
ISN/RPS 
HDL 
LB 
LDL 
LFT 
LLN 
LN 
MedDRA 
gamma glutamyl transferase 
International Society of Nephrology / Renal Pathology Society 
high density lipoprotein 
laboratory 
low Density Lipoprotein 
liver function test 
lower limit of normal 
Lupus Nephritis 
Medical Dictionary for Drug Regulatory Affairs 
mg 
mL 
MMF 
MPA 
milligram(s) 
millilitre(s) 
Mycophenolate mofetil 
Mycophenolic Acid 
PD 
PRR 
PSOC 
PT 
Protocol deviation 
Partial renal response 
Primary System Organ Class 
Preferred Term 
SAE 
SAP 
s.c. 
Serious Adverse Event 
Statistical Analysis Plan 
subcutaneous 
SD 
SMQ 
SoC 
SPP 
TBL 
TEAE 
TG 
UACR 
ULN 
standard deviation 
Standardize MedDRA Queries 
Standard of Care 
Safety Profiling Plan 
total bilirubin 
Treatment Emergent Adverse Event 
triglycerides 
Urine Albumin-to-Creatinine Ratio 
upper limit of normal 


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UPCR 
VS 
Urine Protein-to-Creatinine Ratio 
vital signs 


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1 
Introduction 
This Statistical Analysis Plan (SAP) is for study CAIN457Q12301E1, “A three-year, open-label 
extension study of subcutaneous secukinumab to evaluate the long-term efficacy, safety and 
tolerability in patients with active lupus nephritis”, which is the extension study for 
CAIN457Q12301. 
Data was originally planned to be analyzed by Novartis according to the data analysis section 
12 of study protocol CAIN457Q12301E1 version 00, dated 10-Dec-2021. However, this study 
(CAIN457Q12301E1) along with the core study (CAIN457Q12301) have been terminated early 
by Novartis due to futile results from interim analysis 1 of the core study. There have been no 
safety related reasons for early termination or concerns for the participants in this study. The 
purpose of this version of SAP (SAP amendment 1) is to provide details on the implementation 
of analyses to be reported in the synoptic Clinical Study Report (synoptic CSR).  
Analyses based on this SAP will be executed after all patients complete their planned visits 
based on the early termination plan.  
The statistical methodology is described below and any deviations from the protocol are 
documented. Additional detailed information regarding the analysis methodology is contained 
in the Appendix section. 
Data analysis will be performed by 
 according to this SAP. 
 
1.1 
Study design 
This is a multicenter, optional, open-label, extension study of s.c. secukinumab to evaluate the 
long-term efficacy, safety and tolerability up to three years in patients with lupus nephritis also 
receiving Standard of Care (SoC) regimen. 
The aim of this three-year extension study is to provide treatment with secukinumab for 
participants who complete core study treatment in CAIN457Q12301 and to obtain further long-
term efficacy, safety and tolerability information. 
Due to the futile outcomes from the first interim analysis of the core study, this extension study 
was terminated early and its final analysis will be performed with all available patients by the 
time of study termination. Recruitment in this study was stopped on 26-May-2023 with 31 
participants randomized. Last patient last visit (LPLV) was on 24-Aug-2023. Moreover, 
because of the early termination of the study, 
 analyses will not be 
performed. A synoptic CSR will be generated after the final database lock. 
An outline of study design in present in Figure 1-1.  


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Figure 1-1 
Study design 
 
1.2 
Study objectives, endpoints and estimands  
Table 1-1 shows the objectives and related endpoints as defined in Protocol-V00. Due to the 
early termination of the study: the primary objective will be summarized descriptively 
 
 There was no 
secondary objective defined in the protocol.  
Table 1-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
● To assess the long-term efficacy of 
secukinumab with respect to CRR over time up 
to Week 260 in adults with Lupus Nephritis 
(ISN/RPS class III or IV, with or without co-
existing class V features) participant on 
background of SoC therapy 
● Proportion of participants achieving CRR 
CRR is a composite endpoint defined as: 
 
● Estimated Glomerular Filtration Rate (eGFR) ≥ 60 
mL/min/1.73 m2 or no less than 85% of core Baseline 
values and 
 
● 24-hour Urine-to-Protein Creatinine Ratio (UPCR) ≤ 
0.5mg/mg 


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1.2.1 
Primary estimand(s) 
The estimand is the precise description of the treatment effect and reflects strategies to address 
events occurring during trial conduct which could impact the interpretation of the trial results 
(e.g., premature discontinuation of treatment). 
The attributes of the estimand are: 
• Population: All participants who completed treatment (secukinumab 300 mg or placebo) 
up to Week 104 in the core study and satisfy the inclusion/exclusion criteria to reflect the 
targeted LN population 
• Variable: Complete renal response while on treatment regardless of rescue medication use 
up to Week 260 
• Treatment of interest: secukinumab 300 mg every four weeks  
• Remaining intercurrent events: None. Intercurrent events are included in the variable 
definition. 


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• Population level summary: Proportion of responders summarized over time.  
2 
Statistical methods 
2.1 
Data analysis general information 
Data will be summarized descriptively for all available participants by treatment regimen  
unless otherwise specified.  
Summary statistics for continuous variables will generally include the number of subjects (N), 
mean, standard deviation (SD), median, minimum and maximum.  
For categorical or binary variables, the frequency and percent of subjects in each category will 
be presented. 
2.1.1 
Treatment groups  
Efficacy data will be presented by the following two treatment groups:  
      1.   AIN457 300 mg   
2. Placebo-AIN457 300 mg   
 
Safety data will be presented by the following three treatment groups:  
1. AIN457 300 mg   
2. Placebo-AIN457 300 mg   
3. Any AIN457 300 mg 
 
2.2 
Analysis sets  
The Full Analysis Set (FAS) will be comprised of all subjects who came from the FAS of the 
core study and enrolled in the extension trial. According to the intent to treat principle, subjects 
will be analyzed according to the treatment they have been assigned to during the core study. 
The Safety Set (SAF) includes all subjects who received at least one dose of study treatment in 
the extension trial. Subjects will be analyzed according to the treatment received during the core 
study.  
2.3 
Patient disposition, demographics and other baseline 
characteristics 
2.3.1 
Patient disposition 
The number of subjects enrolled in the extension study will be presented. The number and 
percentage of subjects in the FAS who completed the period up to week 260 and/or the follow 
up visit and who discontinued the study prematurely (including the reason for discontinuation) 
will be presented for each core study treatment group. 
For each protocol deviation (PD) (including COVID-19 PDs, if any), the number and 
percentage of subjects for whom the PD applies will be tabulated. 


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2.3.2 
Demographics and other baseline characteristics 
As this is an extension study, baseline always refers to the core study CAIN457Q12301 baseline. 
Patient demographics and baseline disease characteristic will be derived from the core study 
data, and will be summarized descriptively for FAS by core study treatment groups. 
The following common background and demographic variables will be summarized: 
Continuous variables: 
• Age  
• Height 
• Weight 
• Body mass index (BMI) = (body weight in kilograms) / (height in meters)2 
Categorical variables: 
• Age categories (< 30 yr, ≥30 yr) 
• Gender 
• Race 
• Ethnicity 
• Smoking status at baseline 
Baseline disease characteristics will also be summarized for the following variables: 
• 
Patient’s global assessment of disease activity, UPCR, eGFR, Serum creatinine(mg/dl), 
C3(mg/dl), C4(mg/dl), Anti-dsDNA (geometric mean IU/ml), Standard of care induction 
therapy, corticosteroids (mg/day) at screening, time since first diagnosis of SLE and LN 
(years), and renal biopsy LN classification 
Unless otherwise specified, summary statistics will be presented for continuous variables for 
each treatment group and for all subjects (total) in the FAS. The number and percentage of 
subjects in each category will be presented for categorical variables for each treatment group 
and all subjects (total) in the FAS.  
2.3.3 
Medical History 
Medical history will be presented in a listing. 
 
2.4 
Treatments (study treatment, rescue medication, concomitant 
therapies, compliance) 
2.4.1 
Study treatment / compliance 
The analysis of study treatment data will be based on the safety set. The number of active 
injections received will be presented by core study treatment group. The duration of exposure 
to study treatment will also be summarized by core study treatment group. In addition, the 
number and percentage of patients with cumulative exposure levels (e.g., any exposure, ≥ 108 
week, ≥ 112 weeks, ≥ 116 weeks, ≥ 120 weeks, ≥ 124 weeks, etc.) will be presented. 


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Duration of exposure will be calculated as time from first dose of the treatment in extension to 
the minimum of (last dose of the treatment+ 84 days) and (last visit date). For subjects who 
discontinue treatment, this will be the subject’s last visit. 
Duration of exposure (years) = duration of exposure (days)/ 365.25 
Duration of exposure (100 subject years) = duration of exposure (years)/ 100 
2.4.2 
Concomitant medications 
Concomitant medication will be presented in a listing. 
2.5 
Analysis supporting primary objective(s) 
2.5.1 
Primary endpoint(s) 
Primary endpoint for this study is CRR over time up to Week 260 with the consideration of 
intercurrent events, which is defined in detail at Section 1.2.1. 
2.5.2 
Statistical hypothesis, model, and method of analysis  
No formal statistical testing will be applied for the primary variable. The proportion of 
responders over time will be summarized by treatment group in FAS, using descriptive statistics 
and 95% confidence interval.  
2.5.3 
Handling of missing values not related to intercurrent event 
Not applicable.  
2.5.4 
Sensitivity analyses  
Not applicable. 
2.6 
Analysis supporting secondary objectives  
Not applicable. 
2.7 
Safety analyses 
For all safety analyses, the safety set will be used. All listings and tables will be presented by 
the treatment that patients received in the core study.  
 
2.7.1 
Adverse events (AEs) 
On-treatment period is defined as from the first dose in core study to the last dose in extension 
+84 days. Treatment emergent adverse events (TEAE) (i.e., events started or worsened during 
the on-treatment period) will be summarized.  
The following AE topics will not be provided in summary but will be flagged in the AE listing: 
• All reported AEs that started or worsened before first dose in core study 


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• All reported AEs that started or worsened after last dose in extension + 84 days. 
Confidence intervals for the crude rate will be derived.  
 
 
 
 
 
 
 
 
  
 
 
 
Safety topics of interest, such as risks defined in the Risk Management Plan (RMP) or topics of 
interest regarding signal detection or routine analysis are defined in the Program Case Retrieval 
Sheet.  
The crude incidence rates for the safety topics of interest AEs will be summarized. In addition, 
separate listings will be provided for SAEs. 
Algorithms for date imputations will be provided in Programming Datasets Specifications. 
2.7.2 
Laboratory data 
 
 
  
 
 
 
 


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The following laboratory parameters will be analyzed with respect to numerical Common 
Terminology Criteria for Adverse Events (CTCAE) grades, given in Table 2-2: hemoglobin, 
platelets, white blood cell count, neutrophils, lymphocytes, creatinine, total bilirubin (TBL), 
gamma-glutamyl 
transferase 
(GGT), 
alanine 
aminotransferase 
(ALT), 
aspartate, 
aminotransferase (AST), alkaline phosphatase (ALP), glucose, cholesterol, triglycerides (TG).  
These summaries will be split into hematology and chemistry. 
Table 2-2 
CTCAE grades for laboratory parameters to be analyzed 
CTCAE v4.0 Term 
Grade 1    
Grade 2    
Grade 3    
Grade 4    
HGB decreased 
(Anemia) 
<LLN – 100 g/L 
<100 – 80 g/L 
<80 g/L 
See note below 
Platelet count 
decreased 
<LLN – 75.0 x10e9 /L 
<75.0 - 50.0 x10e9 /L 
<50.0 – 25.0 x10e9 /L 
<25.0 x 10e9 /L 
White blood cell 
decreased 
<LLN - 3.0 x 10e9 /L 
<3.0 - 2.0 x 10e9 /L 
<2.0 - 1.0 x 10e9 /L 
<1.0 x 10e9 /L 
Neutrophil count 
decreased 
<LLN - 1.5 x 10e9 /L 
<1.5 - 1.0 x 10e9 /L 
<1.0 - 0.5 x 10e9 /L 
<0.5 x 10e9 /L 
Lymphocyte count 
decreased 
<LLN - 0.8 x 10e9/L 
<0.8 - 0.5 x 10e9 /L 
 
<0.5 - 0.2 x 10e9 /L 
<0.2 x 10e9 /L 
Creatinine increased* 
 
>1 - 1.5 x baseline;  
>ULN - 1.5 x ULN 
>1.5 - 3.0 x 
baseline; >1.5 - 3.0 x 
ULN 
>3.0 baseline;  
>3.0 - 6.0 x ULN 
>6.0 x ULN 
TBL increased 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x ULN 
>3.0 - 10.0 x ULN 
>10.0 x ULN 
GGT increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALT increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
AST increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALP increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
Glucose increased 
(Hyperglycemia)  
;  
>ULN - 8.9 mmol/L 
>8.9 - 13.9 mmol/L 
>13.9 - 27.8 mmol/L 
>27.8 mmol/L 
Glucose decreased 
(Hypoglycemia) 
<LLN - 3.0 mmol/L 
<3.0 - 2.2 mmol/L 
<2.2 - 1.7 mmol/L 
<1.7 mmol/L 
Cholesterol high 
>ULN - 7.75 mmol/L 
>7.75 - 10.34 mmol/L 
>10.34 - 12.92 mmol/L 
>12.92 mmol/L 
Hypertriglyceridemia 
1.71 - 3.42 mmol/L 
>3.42 - 5.7mmol/L 
>5.7 - 11.4 mmol/L 
>11.4 mmol/L 
Note: Grade 4 Hemoglobin events are defined as life-threatening anemia events and will not be displayed in the table, as a 
numerical range is not provided in the CTCAE. 
*Note: for “creatinine increased” the baseline criteria do not apply. 
 
 
 
 
Summaries for newly occurring or worsening clinically notable lipid abnormalities will also be 
provided cumulatively for each of the following parameters and categories: 
• HDL: 
• <=LLN 
• <0.8 x LLN 
• LDL, cholesterol, triglycerides: 
• >=ULN  
• >1.5 x ULN  


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• >2.5 x ULN 
Newly occurring or worsening liver enzyme abnormalities will also be summarized based on 
the event criteria given in Table 2-3: 
Table 2-3 
Liver-related events 
Parameter 
Criterion 
ALT 
>3xULN; >5xULN; >8xULN;>10xULN, >20xULN 
AST 
>3xULN; >5xULN; >8xULN >10xULN; >20xULN 
ALT or AST 
>3xULN; >5xULN; >8xULN >10xULN; >20xULN 
TBL 
>1.5xULN, >2xULN, >3xULN, 
ALP 
>2xULN, >3xULN. >5xULN 
ALT or AST & 
TBL 
ALT or AST>3xULN & TBL >2xULN; 
ALT or AST >5xULN & TBL >2xULN; 
ALT or AST >8xULN & TBL >2xULN; 
ALT or AST >10xULN & TBL >2xULN 
ALP & TBL 
ALP >3xULN & TBL >2xULN 
ALP >5xULN & TBL >2xULN 
ALT or AST & 
TBL & ALP 
ALT or AST>3xULN & TBL >2xULN & ALP <2xULN (Hy’s Law) 
Note: elevated ALP may suggest obstruction as a consequence of gall bladder or 
bile duct disease; ALP may also be increased in malignancy. FDA therefore terms 
Hy’s Law cases as indicators of pure hepatocellular injury. This does not mean 
that cases of ALT or AST >3xULN & TBL >2xULN & ALP ≥2xULN may not result 
in severe DILI. 
Notes: 
In studies which enrolled subjects with pre-existing liver disease, baseline LFT may be increased 
above ULN; in such a case it is meaningful to add the condition “and worse than baseline” to the 
abnormality criteria 
For a combined criterion to be fulfilled, all conditions have to be fulfilled on the same visit. The 
criteria are not mutually exclusive, e.g. a subject with ALT = 6.42xULN is counted for 
ALT >3xULN and ALT>5x ULN. 
2.7.3 
Other safety data 
2.7.3.1 
ECG data 
A listing of ECG collected in the extension trial will be provided by treatment and by subject. 
2.7.3.2 
Vital signs 
The summary of vital signs will only include treatment emergent data, which are defined as 
those vital sign measurements after the first dose of core study treatment and on or before last 
dose + 84 days in extension. 
 
 
 


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The number and percentage of subjects with newly occurring notable vital signs will be 
presented. Criteria for notable vital sign abnormalities are provided in Table 2-4: 
Table 2-4 
Criteria for notable vital sign abnormalities 
Vital sign (unit) 
Notable abnormalities 
Systolic blood pressure (mmHg) 
>= 140 mmHg or < 90 mmHg 
Diastolic blood pressure (mmHg) 
>=90 mmHg or <60 mmHg 
Pulse (bpm) 
> 100 bpm or <60 bpm 
 
2.7.3.3 
Immunogenicity 
 Not applicable. 
2.8 
Pharmacokinetic endpoints   
Not applicable. 
2.9 
PD and PK/PD analyses 
Not applicable. 
2.10 
Patient-reported outcomes 
Not applicable. 
2.11 
Biomarkers 
Not applicable. 
 
 
 
 
2.13 
Interim analysis 
Not applicable.  
3 
Sample size calculation 
Sample size is based on participants continuing from core study to extension study. 


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4 
Change to protocol specified analyses 
The following significant changes due to early termination of the study are implemented SAP: 
 
1. In section 5.2, the target day corresponding to visit W104E1 has been updated to “Day 
729” to reflect the analyses of this extension study will use the baseline from the core 
study. The protocol keeps the target day of visit W104E1 to “Day 0” to avoid changes in 
operation.  
2. Terminate the study early due to the futile outcomes from the first interim analysis in the 
core study. 
3. Change the Clinical Study Report type from full to abbreviated. 
4. Indicate the CRO 
 will carry out the final analysis.  
5. Exclude intercurrent events for the primary objective. 
 
 
7. Removal of some safety analyses. 
8. Add safety topics of interest AEs safety analyses. 
 
5 
Appendix 
5.1 
Description of efficacy variables 
Complete Renal Response (CRR) 
The CRR will be used to determine efficacy. CRR is a composite endpoint defined as: 
• eGFR ≥ 60 mL/min/1.73m2 or no less than 85% of Baseline 
and 
• 24-hour UPCR ≤ 0.5 mg/mg 
Estimated glomerular filtration rate (eGFR) 
The glomerular filtration rate will be estimated using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) equation (Martínez Martínez et al 2013) based on 
subject gender, age (years) and serum creatinine (mg/dL). 
Central laboratory serum creatinine values will be used for all renal function data analysis. 
Urine Protein-to-Creatinine Ratio (UPCR) 
Urine Protein-to-Creatinine Ratio (UPCR), expressed in mg/mg, will be determined by a central 
laboratory by dividing the protein concentration by the creatinine concentration as measured in 
the urine collected. 


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Depending on the objective to be assessed, the UPCR will be determined using one of the 
following two types of urine collection, 24-hour urine collection or first morning void urinary 
sample. 
Both the 24-hour urine collection and the first morning void will be collected in the subjects' 
home. 
 
5.2 
Visit windows, baseline and post-baseline definitions, missing 
data handling  
Baseline and post-baseline definitions 
In general, a baseline value refers to the core study and is the last measurement made prior to 
administration of the first dose of study treatment in core. Baseline information will be 
presented appropriately in the “by visit” summaries in both safety and efficacy tables.  
A post-baseline value refers to a measurement taken after the first dose of study treatment in 
extension study. 
For early discontinuation visit mapping in different assessments, the early discontinuation week 
will be the next visit of corresponding assessment based on the patients’ last scheduled visit. 
Analysis visit windows 
Analysis visit windows will be used for the data that is summarized by visit; they are based on 
the study visit and evaluation schedule and comprise a set of days around the nominal visit day. 
For any assessment, there are protocol defined scheduled visits around which analysis visit 
windows were created to cover the complete range of days within the study.  
When visit windows are used, all visits will be re-aligned, i.e., they will be mapped into one of 
the visit windows, as in Table 5-1. E.g., if the Week 108 visit of a subject is delayed and occurs 
on Day 802 instead of on Day 760, it will be re-aligned to visit window Week 120. In the case 
of major deviations from the visit schedule, or due to unscheduled visits, several assessments 
of a subject may fall in a particular visit window (either scheduled or unscheduled). Statistical 
approaches to handle multiple assessments in a given visit window are specified below.  
For lab/vital signs, follow-up (F/U) visit is excluded from analysis visit mapping window. Only 
assessments that come as F/U nominal visit will be directly assigned as analysis F/U visit. Other 
assessments that are beyond the last on-treatment visit window (W260) or after nominal F/U 
visit date won't be mapped to any analysis visit. F/U visit will not be included in the summary 
tables by visit. 
Of note, subjects are allowed to have gaps in visits. All data collected will be displayed in 
listings. 


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Table 5-1 
Analysis visit windows 
Analysis 
Visit 
Target 
Day 
Analysis 
Visit 
Window 
Group 1 
Group 2 
Group 3 
W104E1 
729 
716-743 
716-743 
709-743 
709-876 
W108 
757 
744-799 
744-799 
744-799 
 
W120 
841 
800-883 
800-883 
800-876 
 
W132 
925 
884-967 
884-967 
877-974 
877-1044 
W144 
1009 
968-1051 
968-1051 
975-1044 
 
W156 
1093 
1052-
1177 
1052-1177 
1045-
1177 
1045-
1177 
W180 
1261 
1178-
1359 
1178-1359 
1178-
1359 
1178-
1359 
W208 
1457 
1360-
1541 
1360-1541 
1360-
1541 
1360-
1541 
W232 
1625 
1542-
1723 
1542-1723 
1542-
1723 
1542-
1723 
W260 
1821 
≥1724 
≥1724 
≥1724 
≥1724 
 
 
Group 1: Vital Signs, Body Weight, Hematology, 
Clinical Chemistry (exclude eGFR), Coagulation 
Panel, Fasting lipid panel, FMV urine collection 
Group 2: eGFR 
Group 3: 24-hr urine collection 
 
5.3 
Statistical models 
5.3.1 
Summary statistics for binary and categorical data 
Summary statistics for discrete variables will be presented in contingency tables and will 
include count and frequency in each category.  
For 𝑛𝑛 subjects, each at risk to experience a certain event with probablity 𝜋𝜋, the crude incidence 
is estimated as  𝑥𝑥/𝑛𝑛, where 𝑥𝑥 is the number of subjects with the event. 
Absolute and relative frequencies will be displayed as well as 95% confidence interval for the 
relative frequency based on the score method including continuity correction [Newcombe 
(1998)]: 
With 𝑧𝑧 as (1 −𝛼𝛼/2)-quantile of the standard normal distribution (SAS: z= PROBIT (1- 𝛼𝛼/2)), 
𝑛𝑛 as total number of subjects (i.e., number of subjects in the denominator), and 𝑝𝑝 as estimated 
crude incidence (number of subjects with event /𝑛𝑛) and 𝑞𝑞= 1 −𝑝𝑝. 
Then the lower limit is 
(
)
(
)










+
+
+
−
−
−
−
+
×
=
2
2
2
2
1
4
1
2
1
2
,0
max
100
z
n
nq
p
n
z
z
z
np
L
 


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and the upper limit is 
(
)
(
)










+
−
+
−
+
+
+
+
×
=
2
2
2
2
1
4
1
2
1
2
,1
min
100
z
n
nq
p
n
z
z
z
np
U
. 
Note: if 𝐿𝐿> 𝑝𝑝 then 𝐿𝐿= 𝑝𝑝 and if 𝑈𝑈< 𝑝𝑝 then 𝑈𝑈= 𝑝𝑝. 
5.3.2 
Crude incidence and related risk estimates 
For n subjects, each at risk to experience a certain event with probability π, the crude incidence 
is estimated as p=x/n, where x is the number of subjects with the event. 
Absolute and relative frequencies will be displayed as well as 95% confidence interval for the 
relative frequency based on the score method including continuity correction (Newcombe 1998). 
With z as (1-α/2)-quantile of the standard normal distribution (SAS: z = PROBIT(1-α/2), n as 
total number of subjects (i.e. number of subjects in the denominator), and p as estimated crude 
incidence (number of subjects with event / n) it is q=1-p. 
Then the lower limit is 
(
)
(
)










+
+
+
−
−
−
−
+
=
2
2
2
2
1
4
1
2
1
2
,0
max
z
n
nq
p
n
z
z
z
np
L
 
and the upper limit is 
(
)
(
)










+
−
+
−
+
+
+
+
=
2
2
2
2
1
4
1
2
1
2
,1
min
z
n
nq
p
n
z
z
z
np
U
. 
In addition, if L > p then L = p and if U < p then U = p. 
If appropriate, an exact 100*(1-α)% confidence interval (Clopper-Pearson, 1934) will be 
obtained by using the SAS procedure PROC FREQ with the EXACT BINOMIAL statement. 
However, the confidence interval derived via the score method including continuity correction 
will be the default in safety analyses. 
6 
Reference 
ICH E9(R1) Harmonized Guideline: addendum on estimands and sensitivity analysis in 
clinical trials to the guideline on statistical principles for clinical trials. Final version on 20 
November 2019.  
Clopper CJ, Pearson ES (1934). The use of confidence or fiducial limits illustrated in the case 
of the binomial. Biometrika, 26; 404–413. 


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Garwood F (1936). Fiducial limits for the Poisson distribution. Biometrika, 46; 441–453. 
Levin A, Stevens PE, Bilous RW, et al (2013) 'Kidney disease: Improving global outcomes 
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Newcombe, RG. (1998) Two-sided confidence intervals for the single proportion: comparison 
of seven methods. Statistics in Medicine; 17: 857-872. 
Sahai H, Khurshid Anwer (1993). Confidence intervals for the mean of a poisson distribution: 
a review. Biom J, 35 (7); 857-867 
Ulm K (1990). A simple method to calculate the confidence interval of a standard mortality 
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