Clinical trial NCT04300296
Conditions: Lichen Planus: Cutaneous Lichen Planus, Mucosal Lichen Planus and Lichen Planopilaris
Keywords: Lichen planus CLP MLP LPP
Sponsor: Novartis Pharmaceuticals
Start date: 2020-07-27; Completion date: 2022-05-03
Enrollment: 111 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary purpose of the proof of concept study is to elucidate the efficacy of secukinumab in the treatment of adult patients with biopsy-proven lichen planus not adequately controlled by topical therapies, and to assess the safety and tolerability over 32 weeks.

Detailed description:
This was a 32-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial which assessed the efficacy and safety of secukinumab 300 mg in two different dosing regimens: every 4 weeks (Q4W) and every 2 weeks (Q2W) in approximately 111 patients with biopsy-proven forms of lichen planus.

There was a screening period (up to 4 weeks prior to baseline), a treatment period 1 (baseline to Week 16), a treatment period 2 (Week 16 to Week 32) and a follow-up period (8 weeks after Week 32).

Arms: arm 1: Secukinumab 300 mg every 4 weeks provided in pre-filled syringe in cutaneous lichen planus patients arm 2: Placebo in 1ml PFS in cutaneous lichen patients arm 3: Secukinumab 300 mg every 4 weeks provided in pre-filled syringe in mucosal lichen planus patients. arm 4: Placebo 1 ml PFS in mucosal lichen planus patients arm 5: Secukinumab 300 mg every 4weeks provided in pre-filled syringe in lichen planopilaris patients. arm 6: Placebo in 1ml PFS in lichen planopilaris patients arm 7: Non responder patients on placebo in TP 1 received secukinumab 300 mg Q2W in TP 2 arm 8: Non responder patients on placebo in TP 1 received secukinumab 300 mg Q2W in TP 2 arm 9: Non responder patients on placebo in TP 1 received secukinumab 300 mg Q2W in TP 2
Interventions: intervention 1: secukinumab 300 mg Q4W intervention 2: secukinumab 300 mg Q2W intervention 3: Placebo
Intervention descriptions: intervention 1: secukinumab 300 mg administered every four weeks (Q4W) via a pre-filled syringe. intervention 2: secukinumab 300 mg administered every two weeks (Q2W) via a pre-filled syringe. intervention 3: Matching placebo administered via a pre-filled syringe

Protocol documents:
Prot_000.pdf: 
Novartis Research and Development 
AIN457 
Clinical Trial Protocol CAIN457S12201 / NCT04300296
A proof of concept study to evaluate the efficacy, safety 
and tolerability of secukinumab 300 mg over 32 weeks in 
adult patients with biopsy-proven forms of lichen planus 
not adequately controlled with topical therapies - PRELUDE 
Document type: 
Clinical Trial Protocol Amendment 
EUDRACT number: 
2019-003588-24 
Version number: 
02 (Clean) 
Clinical Trial Phase: 
II 
Release date: 
26-Oct-2020
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 2.0 dated 01-Aug-2018 


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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 5 
List of abbreviations ............................................................................................................ 7 
Glossary of terms ............................................................................................................... 10 
Amendment 02 ......................................................................................................................... 12 
Amendment 01 ......................................................................................................................... 13 
Protocol summary .............................................................................................................. 15 
1 
Introduction ....................................................................................................................... 18 
1.1 
Background ............................................................................................................ 18 
1.2 
Purpose .................................................................................................................. 19 
2 
Objectives and endpoints ................................................................................................... 20 
3 
Study design ...................................................................................................................... 22 
4 
Rationale ............................................................................................................................ 25 
4.1 
Rationale for study design ..................................................................................... 25 
4.2 
Rationale for choice of background therapy .......................................................... 27 
4.3 
Rationale for dose/regimen and duration of treatment .......................................... 27 
4.4 
Rationale for choice of control drugs .................................................................... 29 
4.5 
Purpose and timing of interim analyses/design adaptations .................................. 30 
4.6 
Risks and benefits .................................................................................................. 30 
5 
Population .......................................................................................................................... 32 
5.1 
Inclusion criteria .................................................................................................... 32 
5.2 
Exclusion criteria ................................................................................................... 32 
6 
Treatment ........................................................................................................................... 35 
6.1 
Study treatment ...................................................................................................... 35 
6.1.1 
Investigational and control drugs .......................................................... 35 
6.1.2 
Additional study treatments .................................................................. 35 
6.1.3 
Treatment arms/group ........................................................................... 35 
6.1.4 
Treatment duration ................................................................................ 36 
6.2 
Other treatment(s) .................................................................................................. 37 
6.2.1 
Concomitant therapy ............................................................................. 37 
6.2.2 
Prohibited medication ........................................................................... 38 
6.2.3 
Rescue medication ................................................................................ 40 
6.3 
Subject numbering, treatment assignment, randomization .................................... 40 
6.3.1 
Subject numbering ................................................................................ 40 
6.3.2 
Treatment assignment, randomization .................................................. 40 


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6.4 
Treatment blinding ................................................................................................. 41 
6.5 
Dose escalation and dose modification .................................................................. 41 
6.5.1 
Dose modifications ................................................................................ 41 
6.5.2 
Follow-up for toxicities ......................................................................... 41 
6.6 
Additional treatment guidance ............................................................................... 41 
6.6.1 
Treatment compliance ........................................................................... 41 
6.6.2 
Recommended treatment of adverse events .......................................... 42 
6.6.3 
Emergency breaking of assigned treatment code .................................. 42 
6.7 
Preparation and dispensation ................................................................................. 43 
6.7.1 
Handling of study treatment and additional treatment .......................... 43 
6.7.2 
Instruction for prescribing and taking study treatment ......................... 44 
7 
Informed consent procedures ............................................................................................ 45 
8 
Visit schedule and assessments ......................................................................................... 46 
8.1 
Screening ............................................................................................................... 54 
8.2 
Subject demographics/other baseline characteristics ............................................. 54 
8.2.1 
Demography .......................................................................................... 54 
8.2.2 
Prior Lichen Planus medical history and previous therapies ................ 54 
8.2.3 
Smoking history .................................................................................... 55 
8.2.4 
Medical history/current medical conditions .......................................... 55 
8.2.5 
Prior and concomitant medications ....................................................... 55 
8.2.6 
Determination of the tuberculosis status ............................................... 55 
8.3 
Efficacy .................................................................................................................. 55 
8.3.1 
Investigator’s Global Assessment (IGA) .............................................. 55 
8.3.2 
Physician´s assessment of surface area of disease (PSAD) .................. 57 
8.3.3 
Reticulations, erythema and ulcerations (REU) score .......................... 58 
8.3.4 
Lichen planopilaris Activity Index (LPPAI) ......................................... 59 
8.3.5 
Appropriateness of efficacy assessments .............................................. 59 
8.4 
Safety/Tolerability ................................................................................................. 60 
8.4.1 
Laboratory evaluations .......................................................................... 62 
8.4.2 
Pregnancy .............................................................................................. 63 
8.4.3 
Appropriateness of safety measurements .............................................. 63 
8.5 
Additional assessments .......................................................................................... 63 
8.5.1 
Patient Reported Outcomes (PROs) ...................................................... 64 
 
 66 
 
 67 
 
 67 
8.5.5 
Other Assessments ................................................................................ 69 


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9 
Study discontinuation and completion .............................................................................. 69 
9.1 
Discontinuation ...................................................................................................... 69 
9.1.1 
Discontinuation of study treatment ....................................................... 69 
9.1.2 
Discontinuation of study ....................................................................... 70 
9.1.3 
Withdrawal of informed consent ........................................................... 70 
9.1.4 
Lost to follow-up ................................................................................... 71 
9.1.5 
Early study termination by the sponsor ................................................. 71 
9.2 
Study completion and post-study treatment .......................................................... 71 
10 Safety monitoring and reporting ........................................................................................ 72 
10.1 
Definition of adverse events and reporting requirements ...................................... 72 
10.1.1 
Adverse events ...................................................................................... 72 
10.1.2 
Serious adverse events .......................................................................... 74 
10.1.3 
SAE reporting........................................................................................ 75 
10.1.4 
Pregnancy reporting .............................................................................. 75 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 76 
10.2 
Additional Safety Monitoring ................................................................................ 76 
10.3 
Steering Committee ............................................................................................... 76 
11 Data Collection and Database management ...................................................................... 77 
11.1 
Data collection ....................................................................................................... 77 
11.2 
Database management and quality control ............................................................ 77 
11.3 
Site monitoring ...................................................................................................... 78 
12 Data analysis and statistical methods ................................................................................ 78 
12.1 
Analysis sets .......................................................................................................... 78 
12.2 
Subject demographics and other baseline characteristics ...................................... 79 
12.3 
Treatments ............................................................................................................. 79 
12.4 
Analysis of the primary endpoint(s) ...................................................................... 79 
12.4.1 
Definition of primary endpoint(s) ......................................................... 79 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 79 
12.4.3 
Handling of missing values/censoring/discontinuations ....................... 80 
12.4.4 
Sensitivity and Supportive analyses ...................................................... 80 
12.5 
Analysis of secondary endpoints ........................................................................... 80 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) .................................... 80 
12.5.2 
Safety endpoints .................................................................................... 82 
 
 83 
 
 83 
 
 83 
12.5.6 
PD relationships .............................................................................. 83 


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12.5.7 
Patient reported outcomes ..................................................................... 83 
 
 83 
12.7 
Interim analyses ..................................................................................................... 84 
12.8 
Sample size calculation .......................................................................................... 84 
13 Ethical considerations and administrative procedures ...................................................... 86 
13.1 
Regulatory and ethical compliance ........................................................................ 86 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 86 
13.3 
Publication of study protocol and results............................................................... 86 
13.4 
Quality Control and Quality Assurance ................................................................. 86 
13.5 
Protocol adherence ................................................................................................. 87 
13.6 
Protocol amendments ............................................................................................. 87 
14 References ......................................................................................................................... 88 
15 Appendices ........................................................................................................................ 91 
15.1 
Appendix 1: Clinically notable laboratory values and vital signs ......................... 91 
 
 92 
15.3 
Appendix 2: Determination of Tuberculosis status ............................................... 93 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 20 
Table 6-1 
Investigational and control drug ............................................................ 35 
Table 6-2 
Prohibited medication ........................................................................... 38 
Table 8-1 
Assessment Schedule ............................................................................ 47 
Table 8-2 
Investigator's Global Assessment grading ............................................ 56 
Table 8-3 
LPPAI .................................................................................................... 59 
Table 8-4 
Assessments & Specifications ............................................................... 61 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 76 
Table 12-1 
Operating Characteristics on different randomization ratio and 
different response rate assumption ........................................................ 85 
 
 92 
 
 92 
List of figures 
Figure 3-1 
Study design .......................................................................................... 25 
Figure 4-1 
Predicted systemic exposure of the every 2 and every 4 weeks 
dosing intervals during maintenance at the 300 mg dose level ............. 29 


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Figure 12-1 
Operating Characteristics on different randomization ratio and 
different response rate assumption ........................................................ 85 
Figure 15-1 
Tuberculosis screening flowchart ......................................................... 95 
 


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List of abbreviations 
AE 
Adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
β-hCG  
beta-human chorionic gonadotropin 
BDR 
Bioanalytical Data Report 
BSA 
Body Surface Area 
BSL 
Baseline 
CFR 
Code of Federal Regulation 
ClinRO 
Clinician reported outcome 
CLP 
Cutaneous lichen planus 
 
 
CMO & 
PS 
Chief Medical Office and Patient Safety 
CO 
Country organization 
CRA 
Clinical Research Associate 
CRF 
Case report form 
CRO 
Contract Research Organization 
CSR 
Clinical study report 
CTRD 
Clinical Trial Results Database 
CTT 
Clinical Trial Team 
 
 
CVID 
Common variable immunodeficiency 
DDE 
Direct data entry 
DLQI 
Dermatology Life Quality Index  
 
 
EDC 
Electronic Data Capture 
 
 
EMA 
European Medicines Agency 
EOT 
End of treatment 
eSAE 
electronic Serious Adverse Event 
 
 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FFA 
Frontal fibrosing alopecia 
GCP 
Good Clinical Practice 
GCS 
Global Clinical Supply 
GGT 
Gamma-Glutamyl-Transferase  
h 
hour 
H  
Home administrations 
HbA1c 
Hemoglobin A1c 


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HBsAg 
Hepatitis B surface antigen 
HDL 
High density lipoprotein 
HIV 
human immunodeficiency virus 
HRQoL 
Health-related quality of life 
hs-CRP 
High sensitivity C-reactive protein 
IB 
Investigator Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IFU 
Instructions for use 
 
 
IGA 
Investigator’s Global Assessment  
IL-17A 
Interleukin 17A 
IN 
Investigator Notification 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IUD 
Intrauterine device 
IUS 
Intrauterine system 
LDH 
Lactate dehydrogenase 
LDL 
Low density lipoprotein 
LLN 
lower limit of normal 
LLOQ 
Lower limit of quantification 
LP 
Lichen planus 
LPP 
Lichen planopilaris 
LPPAI 
Lichen Planopilaris Activity Index  
MedDRA 
Medical dictionary for regulatory activities 
mg 
milligram(s) 
mL 
milliliter(s) 
MLP 
Mucosal lichen planus 
NCDS 
Novartis Clinical Data Standards 
NCT 
National clinical trial 
NRS 
Numerical rating scale 
OLP 
Oral lichen planus 
OLPSSM 
Oral Lichen Planus Symptom Severity Measure  
OTC 
Over the counter 
PBO 
Placebo 
PD 
Pharmacodynamic(s) 
PFS 
Pre-filled syringe 
 
  
 
  
 
 


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PoC 
Proof-of-concept 
PPD 
Purified protein derivative 
PRO 
Patient reported outcome 
PSAD 
Physician´s assessment of surface area of disease 
PUVA 
Psoralen and Ultraviolet A 
Q2W 
Once every 2 weeks 
Q4W 
Once every 4 weeks 
QFT 
QuantiFERON® TB-Gold test 
QMS 
Quality Management System 
RAS 
Randomized Analysis Set 
RDC 
Remote Data Capture 
REU 
Reticulations, erythema and ulcerations 
RoW 
Rest of the World 
RPM 
Revolutions Per Minutes 
s.c. 
subcutaneous 
SAE 
serious adverse event 
SC 
Steering Committee 
sCR 
serum creatinine 
SD 
standard deviation 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SOP 
Standard Operating Procedures 
SST 
Serum Separator Tubes 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TB 
Tuberculosis 
TBL 
total bilirubin 
TNF 
Tumor necrosis factor 
ULN 
upper limit of normal 
ULQ 
upper limit of quantification 
US 
United States of America 
UVA 
Ultraviolet A 
UVB 
Ultraviolet B 
WHO 
World Health Organization 
Wk 
Week 
WoC 
Withdrawal of Consent 


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Glossary of terms 
Assessment 
A procedure used to generate data required by the study 
Cohort 
A specific group of subjects fulfilling certain criteria 
Control drug 
A study drug 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. 
Dosage 
Dose of the study treatment given to the subject in a time unit (e.g. 100 mg 
once a day, 75 mg twice a day) 
Enrollment 
Point/time of subject entry into the study at which informed consent must be 
obtained (i.e. prior to starting any of the procedures described in the protocol) 
Epoch 
Interval of time in the planned conduct of a study. An epoch is associated with 
a purpose (e.g. screening, randomization, treatment, follow-up), which applies 
across all arms of a study. 
Estimand 
A structured framework that translate the trial objective into a precise definition 
of the treatment effect that is to be estimated 
Healthy volunteer 
A person with no known significant health problems who volunteers to be a 
study participant  
Investigational 
drug 
The study drug whose properties are being tested in the study; this definition is 
consistent with US CFR 21 Section 312.3 and is synonymous with 
“investigational new drug” or “investigational medicinal product”. 
Investigational 
treatment 
All investigational drug(s) whose properties are being tested in the study as 
well as their associated treatment controls. This includes any placebos, any 
active controls, as well as approved drugs used outside of their 
indication/approved dosage or tested in a fixed combination. Investigational 
treatment generally does not include other treatments administered as 
concomitant background therapy required or allowed by the protocol when 
used within approved indication/dosage. 
Medication 
number 
A unique identifier on the label of each study drug package in studies that 
dispense study drug using an IRT system. 
Medication pack 
number 
A unique identifier on the label of each drug package in studies that dispense 
study treatment using an IRT system 
Part 
A single component of a study that contains different objectives or populations 
within that single study. Common parts within a study are: a single dose part 
and a multiple dose part, or a part in patients with established disease and in 
those with newly-diagnosed disease. 
Patient 
An individual with the condition of interest 
Period 
A minor subdivision of the study timeline; divides phases into smaller functional 
segments such as screening, baseline, titration, washout, etc. 
Premature 
subject 
withdrawal 
Point/time when the subject exits from the study prior to the planned completion 
of all study drug administration and assessments; at this time all study drug 
administration is discontinued and no further assessments are planned. 
Randomization 
number 
A unique identifier assigned to each randomized subject, corresponding to a 
specific treatment arm assignment 
Screen Failure 
A subject who is screened but is not treated or randomized 
Stage 
A major subdivision of the study timeline; begins and ends with major study 
milestones such as enrollment, randomization, completion of treatment, etc. 
Study completion 
Point/time at which the subject came in for a final evaluation visit or when study 
drug was discontinued whichever is later. 


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Study drug 
discontinuation 
Point/time when subject permanently stops taking study drug for any reason; 
may or may not also be the point/time of premature subject withdrawal. 
Study treatment 
Any drug administered to the study participants as part of the required study 
procedures; includes investigational drug (s), control(s) or non-investigational 
medicinal product(s) 
Study treatment 
discontinuation 
When the subject permanently stops taking study treatment prior to the defined 
study treatment completion date 
Subject 
An individual who has consented to participate in this study. The term Subject 
may be used to describe either a healthy volunteer or a patient. 
Subject number 
A unique number assigned to each subject upon signing the informed consent. 
This number is the definitive, unique identifier for the subject and should be 
used to identify the subject throughout the study for all data collected, sample 
labels, etc. 
Treatment 
number 
A unique identifier assigned in non-randomized studies to each dosed subject, 
corresponding to a specific treatment arm  
Variable 
Information used in the data analysis; derived directly or indirectly from data 
collected using specified assessments at specified timepoints. 
Withdrawal of 
consent (WoC) 
Withdrawal of consent from the study is defined as when a subject does not 
want to participate in the study any longer, and does not want any further visits 
or assessments, and does not want any further study related contact, and does 
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Amendment 02 
Amendment rationale  
The reason for this amendment is to allow the assessment of biopsies by local pathologists.  
Other, minor points have been updated or corrected as well to further optimize the clinical trial 
protocol. 
Changes to the protocol 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined font for insertions. 
Changes to the protocol include: 
• Section 8.5.4 has been modified to allow the assessment of biopsies by local pathologists 
Editorial revisions, clarifications and corrections have also been made throughout the protocol. 
None of the changes are due to safety concerns and none of the changes have an impact on the 
conduct of the trial or alter in any way the treatment of study subjects.  
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol are non-substantial and do not require IRB/IEC 
approval prior to implementation. 
The changes herein do NOT affect the trial specific model ICF. 
 
 


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Summary of previous amendments  
Amendment 01 
Amendment rationale  
There are three major reasons for this amendment:  
The first one is an update of the IGA score specifications. Certain criteria of the score have been 
changed in a way that the score in its amended version is more specific regarding certain aspects 
of the disease, its clinical application has become easier and it now covers cases which were 
not covered before.   
The second major reason is to allow the use of historical biopsies (if available) at screening for 
patients of all three subtypes of lichen planus instead of allowing it for the lichen planopilaris 
cohort only. This makes the trial more patient friendly and reduces the need for biopsies. 
The third major reason is to adapt the protocol to pandemic/ epidemic related challenges and 
their potential longer lasting impact on the conduct of clinical trials. In case of a pandemic/ 
epidemic, sites are given the opportunity for home shipment of study drug and urine pregnancy 
tests, as well as phone calls for safety assessment. The purpose of this is to protect patients as 
well as site staff by reducing personal exposure and thereby reducing the risk for transmission 
of infectious diseases (e.g. COVID-19) while maintaining adequate safety monitoring. 
Other, minor points have been updated or corrected as well to further optimize the clinical trial 
protocol. 
Changes to the protocol 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined for insertions. 
Changes to the protocol include: 
• Table 2-1 has been modified to enlarge Patient assessment of itch to all LP sub-types 
• Section 3, End of treatment and End of study have been further defined and flow of 
visits clarified, criteria for re-screening have been clarified  
• Section 5.2, Inflammatory Bowel Disease has been added as an example to Exclusion 
criterion #15 
• Section 6.1.3 has been corrected to enlarge the use of historical biopsy for inclusion to 
all LP subtypes 
• Section 6.2.1, Section 6.2.2, List of allowed and forbidden medications has been 
corrected and clarified 
• Section 6.7 and Section 6.7.2 have been modified to allow study drug shipment to 
subjects and home administration, as well as remote contact to collect safety information 
in case of pandemic / epidemic event 


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• Section 8 and Section 8.4 have been modified to allow study drug shipment to subjects 
and remote contact to collect safety information in case of pandemic / epidemic event 
• Section 8, End of treatment and End of study have been further defined and flow of 
visits clarified, criteria for re-screening have been clarified,  
• Section 8.1, criteria for re-screening have been clarified 
• Table 8-1 has been modified to enlarge Patient assessment of itch to all LP sub-types 
and to enlarge the use of historical biopsy for inclusion to all LP subtypes, End of 
treatment and End of study have been further defined, and flow of visits clarified; timing 
of urine pregnancy tests has also been corrected 
• Table 8-2, the Investigator’s Global Assessment grading has been modified 
• Section 8.3.2, Assessment scoring for Physician’s assessment of surface area of disease 
has been corrected 
• Section 8.4.2, Section 8.5.4 Timing of urine pregnancy tests has been corrected 
• Section 8.5.4 has been corrected to enlarge the use of historical biopsy for inclusion to 
all LP subtypes 
• Section 9.1.1, Section 9.1.2, Section 9.2, End of treatment and End of study have been 
further defined and flow of visits clarified  
• Section 10.1.4, Need for requiring a signed pregnancy ICF to follow up on any 
pregnancy has been added 
Editorial revisions, clarifications and corrections have also been made throughout the protocol. 


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Protocol summary 
 
Protocol number 
CAIN457S12201 
Full Title 
A proof-of-concept study to evaluate the efficacy, safety and tolerability of 
secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven 
forms of lichen planus not adequately controlled with topical therapies - 
PRELUDE 
Brief title 
Study of efficacy and safety of secukinumab 300 mg in adult patients with 
biopsy-proven forms of lichen planus 
Sponsor and 
Clinical Phase 
Novartis/Phase II 
Investigation type 
Drug 
Study type 
Interventional 
Purpose and 
rationale 
Lichen planus (LP) is an inflammatory disease affecting different locations of 
the body (skin, oral cavity, genitalia, scalp, and nails).  
Current therapies are mostly symptomatic. However, 30-50% of patients are 
refractory to available therapies and experience high burden of disease due to 
lack of clinical control, as well as significant psychological discomfort and 
social disability resulting in profoundly impaired quality of life.  
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-
group trial assessing the efficacy and safety of secukinumab 300 mg in two 
different dosing regimens in patients with biopsy-proven forms of lichen 
planus, for which no systemic therapy is currently approved and which could 
be eligible for treatment with secukinumab. 
Primary 
Objective(s)  
The primary objective of this study is to evaluate the efficacy secukinumab 
when compared to placebo after 16 weeks of treatment, by comparing the 
proportion of patients achieving Investigator's Global Assessment (IGA) 
response where IGA response is defined as achievement of absolute IGA 
score less or equal 2 (IGA ≤2).  
Secondary 
Objectives 
Objective 1: to evaluate the efficacy of secukinumab 300 mg Q4W compared 
to placebo throughout 16 weeks in Treatment Period 1 and to evaluate the 
long term efficacy of secukinumab 300 mg Q4W throughout 32 weeks in 
Treatment Period 2 and evaluate the efficacy of secukinumab 300 mg Q2W 
in Treatment Period 2 by Investigator's Global Assessment (IGA), 
Dermatology Life Quality Index (DLQI), Physician Assessment of Surface 
Area of Disease (PSAD) for Skin Disease, Patient assessment of itch 
(Numerical Rating Scale - NRS), Reticular Erythematous Ulcerative (REU) 
score, Oral Lichen Planus Symptoms Severity Measure (OLPSSM) score, 
Patient assessment of pain (NRS), LPP Activity Index (LPPAI), SCALPDEX 
Questionnaire. 
Objective 2: to assess the safety and tolerability of secukinumab in subjects 
with lichen planus by adverse events (AEs), laboratory values, vital signs from 
baseline to end of study visit.  
Study design 
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-
group study in approximately 108 patients with biopsy-proven lichen planus. 
The study consists of: Screening (up to 4 weeks), Treatment Period 1 (16 
weeks), Treatment Period 2 (16 weeks). Subjects who prematurely 


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discontinue the study, or who complete the study, will enter a post-treatment 
Follow-Up period (8 weeks).  
Population 
The study population will consist of adult subjects (≥ 18 years) with biopsy-
proven lichen planus. It is planned to randomize approximately 108 subjects 
in approximately 36 study sites worldwide. At randomization, the subjects will 
be assigned to one of the 3 cohorts (predominant cutaneous lichen planus 
(CLP), predominant mucosal lichen planus (MLP) and lichen planopilaris 
(LPP)) according to the clinical features present.  
Key Inclusion 
criteria 
1. Written informed consent must be obtained before any assessment is 
performed. 
2. Female and male patients ≥ 18 years of age.  
3. Subjects must have biopsy-confirmed forms of cutaneous lichen planus 
(CLP), mucosal lichen planus (MLP), or active lichen planopilaris (LPP) eligible 
for systemic therapy based on the following criteria: 
· Rated IGA of ≥ 3 (moderate or severe) at screening and baseline AND 
· Inadequate response to topical corticosteroids of high - ultrahigh potency in 
the opinion of the investigator  
Key Exclusion 
criteria 
1. Clinical history suspicious for lichenoid drug eruption. 
2. Lichen planus pigmentosus. 
3. Clinical picture or history suspicious of paraneoplastic mucosal lichen 
planus. 
4. Subjects whose lichen planus is a predominantly bullous variant. 
5. Mucosal lichen planus of the oral cavity or gastrointestinal involvement 
requiring the patient to use parenteral nutrition or feeding tube. 
6. Clinical picture of burnt-out cicatricial alopecia (alopecia of Brocque)  
7. Patients diagnosed with frontal fibrosing alopecia (FFA) without active 
patches of LPP. 
8. Previous exposure to any other biologic drug directly targeting IL-17A or IL-
17RA (e.g. ixekizumab or brodalumab) or IL-23/p19 (e.g. tildrakizumab, 
guselkumab, risankizumab).  
9. Hepatitis C antibody positive at screening unless viral load is 0. 
Study treatment 
1. Secukinumab 300 mg, provided as 2 s.c. injections of 1 ml prefilled 
syringe (PFS). Each 1 ml syringe contains 150 mg secukinumab. 
2. Placebo, provided as 2 s.c. injections of 1 ml prefilled syringe (PFS). 
Efficacy 
assessments 
Efficacy assessments related to the primary and secondary objectives 
include: 
Clinician Reported Outcomes (ClinRO) assessed by the investigator 
• 
Investigator’s Global Assessment (IGA) 
• 
Physician Assessment of Surface Area of Disease (PSAD) 
• 
Reticulation, Erythema and Ulcerations score (REU) 
• 
Lichen Planopilaris Activity Index (LPPAI) 
Patient reported outcomes (PRO) assessed by the subject: 
 
 
 
 


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• 
Patient assessment of itch (NRS) 
• 
Patient assessment of pain (NRS) 
• 
Oral Lichen Planus Symptom Severity Measure (OLPSSM) 
• 
Dermatology Life Quality Index (DLQI) 
 
 
• 
SCALPDEX 
 
 
 
 
Key safety 
assessments 
• 
Evaluation of all Adverse Events (AEs) and Serious AEs (SAEs) 
• 
Physical examination 
• 
Vital signs 
• 
Laboratory evaluations (e.g. hematology, clinical chemistry) 
 
 
  
• 
Pregnancy 
Other 
assessments  
 
 
 
 
Data analysis 
In each cohort, for secukinumab 300 mg and placebo treatment groups, the 
proportion of subjects classified as IGA responders after 16 weeks of 
treatment, will be modeled with a binomial distribution. A neutral, non-
informative Beta (1/3, 1/3) distribution will be used as the prior for the 
response rate for secukinumab and placebo treatment groups. Based on the 
priors and the observed primary outcome, posterior distributions for the 
response rate in secukinumab and placebo treatment groups will be 
computed respectively for each cohort. The posterior distribution of the 
difference of response rates over placebo will be obtained by simulations. 
The posterior probabilities for a positive treatment difference will 
be assessed according to the dual efficacy criteria as a guide to 
decision making. In each cohort, secukinumab treatment will be assessed 
separately in comparison to the placebo group. Subjects who do not 
complete the 16-week treatment will be considered as non-responders.  
Key words 
Lichen planus, LP, CLP, MLP, LPP, IL-17A, monoclonal antibody, AIN457, 
secukinumab, itch, pain, efficacy, safety 


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1 
Introduction 
1.1 
Background 
Lichen planus (LP) is a mucocutaneous, inflammatory disease of unknown etiology. First 
described in 1869 and deriving its name from the Greek word lεixήn, for ‘tree moss’, and the 
Latin word planus, for ‘planar’, lichen planus is a relatively uncommon and heterogeneous 
disorder that typically develops in middle-aged adults affecting the skin, the mucosae, or both 
(Tziotzios et al 2018). It is recurrent, and can present in different clinical subtypes based on the 
morphology of the lesions and the site of involvement. 
Skin lesions of lichen planus (cutaneous lichen planus, CLP) are characterized by a subacute or 
chronically progressive appearance of polygonal purple papules often associated with severe 
itch. Mucosal lesions (mucosal lichen planus, MLP) present with usually bilateral white 
striations or plaques, either symptomatic or extremely painful due to their erosive nature, and 
localized in different areas (buccal mucosa, tongue and gingivae, genitalia, conjunctiva or 
esophagus). Lichen planopilaris (LPP) is considered a follicular variant of CLP and develops 
with active patches that, if untreated, lead to irreversible scarring and alopecia. LPP has a sexual 
predilection for females and can also be induced by hair transplantation or cosmetic facial 
surgery due to peri-operative immune-inflammatory responses (Gorouhi et al 2014). 
Lichen planus (LP) estimated prevalence is in the range of 0.1 to 4 percent of the general 
population (Zakrzewska et al 2005). Oral or genital involvement occurs in 60-70% of patients, 
and it may be the sole manifestation of disease in 20-30% of patients. 
The refractory nature of the disease, and the potential of the lesion to become erosive, atrophic, 
or even carcinogenic, correlates with patient's poor quality of life because of the associated pain 
and discomfort. A study assessing DLQI (Balci and Inandi 2008), reported that patients with 
lichen planus describe the impact of the disease on the quality of life comparably to patients 
with psoriasis. 
Histologically, the disease shows apoptosis of keratinocytes, acanthosis, hypergranulosis, 
vacuolating degeneration of the basal layer of the epithelium and a lymphocytoid, cell-rich 
infiltrate in the upper dermis (Cassol-Spanemberg et al 2019). An important entity in the 
differential diagnosis of lichen planus are lichenoid drug reactions, which can be virtually 
indistinguishable from cutaneous lichen planus both clinically and histopathologically. 
There are no established guidelines for lichen planus treatment, and as yet the pathogenesis and 
potential therapeutic targets of the disease remain poorly understood. Conventional therapies 
primarily aim at healing of erosive or atrophic lesions and relieving symptoms such as itch 
(CLP) or pain (MLP). Current clinical practice utilizes topical and systemic corticosteroids, 
retinoids, calcineurin inhibitors (such as cyclosporine, tacrolimus and pimecrolimus), and in 
some cases light therapy. 
Topical corticosteroids have been utilized historically as first-line drugs, while systemic 
treatments are reserved for patients with disease that is more widespread, unresponsive to 
topical treatment or in case of acute exacerbations (Thongprasom and Dhanuthai 2008). 
Despite the etiology of lichen planus being unclear, the abundance of the lymphocytic T cell 
infiltrate supports the participation of cellular immunity with both helper and cytotoxic T cells 


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playing a vital role in its pathogenesis. A delayed hypersensitivity immune reaction, in which 
the release of cytokines by activated T cells leads to the attraction of other immune cells and to 
the destruction of keratinocytes by cell-mediated cytotoxicity, has been implicated in the 
pathogenesis of lichen planus (Shaker and Hassan 2012). 
Notably, every step mediated by T cells in the pathogenesis of lichen planus is amendable for 
interruption, and recent innovations in biologic therapies allows targeting several of these steps. 
In fact, several anecdotal cases have been described, providing evidence of therapeutic benefit 
for patients undergoing biologic therapies (Zhang et al 2011). 
Recently, a case report showed the potential of biologic agents targeting the IL-23/Th17 axis to 
induce clinical remission and strong improvements on a cellular/molecular level in 5 patients 
with steroid refractory lichen planus (Solimani et al 2019), corroborating numerous previous 
findings and suggesting a key role for IL-17A in the pathogenesis of lichen planus. It also 
showed the presence of IL-17A producing Th17 as well as Tc17 cells in lichen planus lesions. 
In fact, several papers described elevated serum concentrations of IL-17A and increased 
numbers of peripheral and lesional Th17 cells in patients with mucocutaneous and oral lichen 
planus, as well as upregulation of IL-17A and Th17-derived cytokines (Schmidt et al 2018, 
Gueiros et al 2018). 
Secukinumab (AIN457) is a recombinant high-affinity fully human monoclonal anti-human IL-
17A antibody of the immunoglobulin (Ig) G1/κ-class. Secukinumab binds to human IL-17A 
and neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine of a newly defined 
subset of inflammatory T cells, the Th17 cells which, , are pivotal in multiple autoimmune and 
inflammatory processes. IL-17A is mainly produced by memory effector CD4+ and CD8+ T 
lymphocytes and is recognized as one of the principal pro-inflammatory cytokines in immune 
mediated inflammatory diseases. Its neutralization is expected to treat the underlying 
pathophysiology of immune mediated disease, and as a consequence provide relief of 
symptoms. 
Secukinumab (Cosentyx®) with a recommended dose of 300 mg was approved in 2014 in Japan, 
in 2015 in the US, EU and Switzerland for the treatment of moderate to severe plaque psoriasis 
in adults. Secukinumab is also approved for the treatment of adult patients with psoriatic 
arthritis or ankylosing spondylitis. Secukinumab is available as a powder for solution for 
injection, and as a solution of 150 mg in 1 mL for injection in pre-filled syringe or auto-injector. 
The Investigator’s Brochure (IB 2020) provides a more detailed review of the pre-clinical and 
clinical information on secukinumab. 
Secukinumab has proven to be a suitable therapeutic option for immune mediated disorders, 
and based on the available scientific evidence and case reports, secukinumab has the potential 
to be an effective therapy for patients with moderate to severe lichen planus. 
The aim of the present study is to assess the efficacy, safety,
 and tolerability 
of two dose regimens of secukinumab in patients with moderate to severe lichen planus. 
1.2 
Purpose 
The purpose of this proof-of-concept study is to elucidate the efficacy of secukinumab in the 
treatment of adult patients with biopsy-proven lichen planus not adequately controlled by 
topical therapies, and to assess the safety and tolerability over 32 weeks. 


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Lichen planus (LP) is a chronic, inflammatory condition affecting different locations of the 
body (skin, oral cavity, genitalia, scalp, and nails), sometimes concomitantly.  
Current therapies used for lichen planus are mostly symptomatic and utilizes wide-spectrum 
immunosuppressive or anti-inflammatory topical or systemic agents. However, 30-50% of 
patients are refractory to current therapies and experience a higher burden of disease due to lack 
of clinical control, as well as significant psychological discomfort and social disability resulting 
in profoundly impaired quality of life.  
These patients may benefit from a systemic, targeted therapy selectively inhibiting IL-17A, a 
key player in the skin inflammatory cascade. This study will evaluate the therapeutic efficacy 
of secukinumab in treating three well-defined subtypes of lichen planus, for which no systemic 
therapy is currently approved and which could be eligible for treatment with secukinumab. 
2 
Objectives and endpoints 
Table 2-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
• 
To demonstrate the clinical efficacy of 
secukinumab 300 mg every 4 weeks (Q4W) in 
subjects with cutaneous lichen planus (CLP), 
mucosal lichen planus (MLP), or lichen 
planopilaris (LPP) inadequately controlled by 
topical therapies, with respect to improvement 
in Investigator’s Global Assessment (IGA) score 
by Week 16, compared to placebo. 
• 
Achievement of IGA response at Week 
16 
Patients diagnosed with biopsy-proven 
forms of CLP, MLP or LPP will be 
considered responders if they achieve an 
absolute IGA score ≤2 at Week 16 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
• 
The secondary objectives of this trial comprise 
the following: 
- evaluate the efficacy of secukinumab 300 mg 
Q4W compared to placebo throughout 16 
weeks in Treatment Period 1; 
- evaluate the long term efficacy of 
secukinumab 300 mg Q4W throughout 32 
weeks in Treatment Period 2; 
- evaluate the efficacy of secukinumab 300 mg 
Q2W in Treatment Period 2; 
- evaluate the safety profile of secukinumab 300 
mg throughout the duration of the study. 
Detailed assessments are described the next 
section. 
 
All subtypes 
Investigator's Global Assessment (IGA) 
• 
Achievement of 2 points improvement in 
the IGA score from baseline to Week 16 
and 32, and throughout the duration of 
the study 
Achievement of IGA 0/1 at Week 16 and 
32, and throughout the duration of the 
study 


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Objective(s) 
Endpoint(s) 
• 
Dermatology Life Quality Index (DLQI)  
• 
Absolute and relative change in DLQI 
from baseline to Week 16 and 32, and 
throughout the duration of the study 
Achievement of DLQI 0/1 score at Week 
16 and 32, and throughout the duration 
of the study 
• 
Patient assessment of itch (NRS) 
• 
Absolute and relative change in NRS 
from baseline to Week 16 and 32, and 
throughout the duration of the study 
• 
Patient assessment of pain (NRS) 
• 
Absolute and relative change in NRS 
from baseline to Week 16 and 32, and 
throughout the duration of the study 
• 
To assess the safety and tolerability of 
secukinumab in subjects with lichen planus. 
• 
Adverse events, laboratory values, vital 
signs 
Cutaneous Lichen Planus (CLP) 
 
• 
Physician Assessment of Surface Area of 
Disease (PSAD) for Skin Disease 
• 
Absolute and relative change in PSAD 
from baseline to Week 16 and 32, and 
throughout the duration of the study 
Mucosal Lichen Planus (MLP) 
 
• 
Reticular Erythematous Ulcerative (REU) score 
• 
Absolute and relative change in REU 
score from baseline to Week 16 and 32, 
and throughout the duration of the study 
• 
Oral Lichen Planus Symptoms Severity 
Measure (OLPSSM) score 
• 
Absolute and relative change in 
OLPSSM score from baseline to week 16 
and 32, and throughout the duration of 
the study 
Lichen Planopilaris (LPP) 
 
• 
LPP Activity Index (LPPAI) 
• 
Absolute and relative change in LPPAI 
score from baseline to Week 16 and 32, 
and throughout the duration of the study 
• 
SCALPDEX Questionnaire 
• 
Absolute and relative change in 
SCALPDEX Questionnaire score from 
baseline to Week 16 and 32, and 
throughout the duration of the study 


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3 
Study design 
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial 
assessing the efficacy and safety of secukinumab 300 mg in two different dosing regimens in 
patients with biopsy-proven forms of lichen planus. 


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The study consists of three cohorts (one cohort per lichen planus subtype: cutaneous lichen 
planus (CLP), mucosal lichen planus (MLP) and lichen planopilaris (LPP)) and 4 study periods 
as illustrated in Figure 3-1. 
Patients are assigned to one of the three cohorts based on their predominant subtype and 
undergo a biopsy to confirm the clinical diagnosis at the screening visit: 
• Predominantly cutaneous lichen planus 
• Predominantly mucosal lichen planus 
• Lichen planopilaris 
Each cohort will follow the same study design across the 4 periods: 
• Screening Period: up to 4 weeks prior to baseline 
• Treatment Period 1: baseline to Week 16 
• Treatment Period 2: Week 16 to Week 32 
• Follow-up: 8 weeks after Week 32 
Screening period: 
A screening period of up to 4 weeks is used to assess patient´s eligibility for the trial and to 
washout/adjust prohibited medications. The screening period covers the time from the signature 
of informed consent/screening visit (-4 weeks) to the randomization visit (Week 0).  
Patients can be re-screened if the patient fails the initial screening due to a transient condition 
(not related to LP) or due to an insufficient prohibited medication washout period. Subjects can 
be re-screened only once and no re-screening procedure should be performed prior to re-
consenting the subject. Patients may also be rescreened at a later time if site closures or other 
logistical issues prevent randomization as planned. Patients presenting with a reduction in the 
IGA score between screening and baseline, with the IGA not qualifying as moderate or severe 
at the baseline visit (i.e., IGA score of 2, 1 or 0), will not be eligible for re-screening. 
Treatment Period 1: 
Treatment Period 1 is placebo-controlled and covers the time from Week 0 (randomization visit) 
to Week 16. Patients who meet all eligibility criteria are randomized in a 2:1 ratio to one of the 
following two treatment arms within their cohort: 
• Secukinumab 300 mg every 4 weeks arm: subjects receive a weekly induction treatment 
followed by secukinumab 300 mg every 4 weeks. 
• Placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks arm: subjects 
receive matching placebo injections. 
Thirty-six patients will be randomized per cohort, 24 to active and 12 to placebo treatment, 
which means that the study will enroll approximately 108 subjects in total. 
In Treatment Period 1 all subjects receive weekly subcutaneous injections of blinded study drug 
(either 300 mg secukinumab or placebo) at weeks 0, 1, 2, 3 and 4. Thereafter the frequency of 
blinded study drug injections for all subjects is every 4 weeks up to Week 16. Home 
administration of study drug is not allowed during Treatment Period 1. Subjects who complete 
Treatment Period 1 roll over to Treatment Period 2 at the week 16 visit. The only exception are 
subjects from the placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks arm, 


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who achieve spontaneous remission at the Week 16 visit. Spontaneous remission is defined as 
an IGA of 0 or 1 at Week 16. These subjects do not proceed to Treatment Period 2 to avoid 
unnecessary treatment. Instead they will directly enter the Follow-up Period after the Week 16 
visit. 
Treatment Period 2: 
Treatment Period 2 starts at the Week 16 visit and covers the time until the Week 32 visit. 
Depending on the treatment arm, subjects receive the following treatments: 
• Secukinumab 300 mg every 4 weeks arm: subjects receive continued treatment with 
secukinumab 300 mg every 4 weeks plus matching placebo injections to maintain 
treatment blinding. 
• Placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks arm: subjects 
are switched to active treatment with secukinumab 300 mg every 2 weeks including an 
induction starting at Week 16, with the exception of subjects achieving remission by 
Week 16. 
The Week 16 injection is the first injection of Treatment Period 2. 
Treatment remains blinded during Treatment Period 2. This means that, starting at the Week 16 
visit, all subjects receive an induction consisting of weekly blinded study drug injections (either 
secukinumab 300 mg or placebo) at weeks 16, 17, 18, 19 and 20, followed by blinded study 
drug injections every 2 weeks, either secukinumab 300 mg alternating with placebo every 2 
weeks (secukinumab 300 mg every 4 weeks arm) or secukinumab 300 mg every 2 weeks 
(placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks arm) until week 30. 
The last study drug injection is administered at Week 30. The end of Treatment Period 2 is 
Week 32. After Week 32, all subjects enter the Follow-up Period.  
Subjects who discontinue study treatment prematurely for any reason other than withdrawal of 
informed consent should not be considered as discontinued from the study. Subjects should 
continue attending planned site visits and perform study assessments until the last visit of the 
treatment period during which they discontinue (Week 16 or Week 32).  
Subjects, whether they are willing to continue attending further study visits or not, should attend 
the End of Treatment visit (EOT) of the study period during which they discontinued (EOT 1 
for discontinuation during Treatment Period 1 and EOT 2 for discontinuation during Treatment 
Period 2). EOT1 should be performed 4 weeks after last dose of study, EOT2 should be 
performed 2 weeks after last dose of study drug. See Section 9.1 for further details. 
Follow-up: 
There is an 8-week Follow-up Period after Week 32. The End of Study is reached at Week 40. 
If a subject discontinues study during Follow-up period, visit Week 40 has to be performed. 
 
 


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Figure 3-1 
Study design 
 
4 
Rationale 
4.1 
Rationale for study design 
The double-blind, parallel, randomized, placebo-controlled design of this trial enables the 
evaluation of the efficacy and safety of secukinumab 300 mg in two different dosing regimens 
in three selected subtypes of lichen planus in an adequate and controlled setting. 
The rationale to assign the subjects to subtype-specific cohorts and to monitor them in a parallel-
group fashion is to assess the efficacy and safety of secukinumab in each subtype individually, 
using subtype-specific assessments and scores. There is broad pathophysiological overlap 
between the three selected subtypes (e.g. dominant role of T cells, presence of Th17 and Tc17 
cells, overexpression of IL-17A in lesions in an encouraging case report on the use of 
secukinumab in lichen planus; Solimani et al 2019) giving strong evidence for a role of IL-17A 
in the pathophysiology of all three subtypes. Furthermore, there is broad clinical overlap 
between the three subtypes, especially between CLP and MLP subtypes, with many patients 
presenting concomitant symptoms and lesions. At the same time each subtype presents at 
different anatomical regions and with distinct clinical features and symptoms, e.g. ulceration 
can be present in the mucosal subtype but not in the cutaneous, whereas itching is highly 
relevant in patients with CLP but not in patients with MLP, or hair follicle inflammation, which 
is the unique feature of LPP. Patients are divided into three cohorts, according to their 
predominant clinical subtype in order to apply subtype-specific assessments. By using this 
design the trial is also able to collect data on the non-predominant ("concomitant") subtype, 
e.g. data on cutaneous lesions in a patient who is enrolled in the predominantly mucosal lichen 


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planus cohort. This ensures optimal usage of all available patient data. Since clinical sites with 
a special focus on the treatment of lichen planus usually see patients of all 3 selected subtypes, 
it also offers an operational advantage for sites to have the opportunity to enroll patients of all 
subtypes in one bundled trial. In addition, this "basket trial" approach enables pooled efficacy 
and safety assessment across all three subtypes. 
The randomization process ensures a comparable and balanced profile of patients across 
treatment arms. The reason to have a 2:1 randomization favoring active treatment in Treatment 
Period 1 is to give more patients the opportunity to receive active treatment with secukinumab 
300 mg every 4 weeks initially, during the first 16 weeks of the trial. Due to the convincing 
preclinical and initial clinical evidence outlined in the background section, the likelihood for 
efficacy of secukinumab in lichen planus is high. Moreover, there is no scientific evidence that 
would suggest that the safety profile of secukinumab in patients with lichen planus differs from 
the favorable safety profile observed in the extensive safety database of secukinumab in the 
currently approved indications (psoriasis, psoriatic arthritis and ankylosing spondylitis). 
Treatment Period 1 has a placebo-controlled, double-blind design and a duration of 16 weeks. 
The rationale for this is that it allows the assessment of the efficacy and safety of secukinumab 
300 mg in the three selected subtypes in comparison to placebo in an adequate setting. Week 
16 represents a widely used and well-accepted timing for the assessment of the primary endpoint 
in secukinumab clinical trials in several inflammatory skin diseases such as psoriasis, 
hidradenitis suppurativa or atopic dermatitis. Standards for the timing of the assessment of the 
primary endpoint are not yet well established for clinical research in lichen planus, however, 
other trials conducted in this field have used comparable durations: Hazra et al. compared 
systemic betamethasone to methotrexate for 12 weeks (Hazra et al 2013), or enoxaparin was 
compared to methotrexate for 24 weeks (Lunge et al 2016). 
During Treatment Period 2, subjects who have been on active treatment in Treatment Period 1 
receive continued active treatment in the same dosing regimen (secukinumab 300 mg every 4 
weeks) until Week 32. This allows the collection of longer term efficacy and safety data beyond 
16 weeks of treatment. Subjects who have been on placebo treatment in Treatment Period 1 are 
switched to active treatment with secukinumab 300 mg every 2 weeks (starting with the regular 
weekly induction). This enables placebo treated patients to receive active treatment during the 
trial as well. Furthermore it allows the assessment of efficacy and safety of the 2-weekly dosing 
regimen in lichen planus. Subjects randomized to the placebo arm who achieve spontaneous 
clinical remission, which is defined as an IGA of 0 or 1, do not roll over to Treatment Period 2, 
instead they directly enter the Follow-up Period. The rationale for this is to avoid unnecessary 
treatment for these patients in Treatment Period 2. An IGA of 0/1 means that there is no or only 
minor disease activity left, and therefore, no need for a systemic treatment. This design may 
lead to partial unblinding, since patients who continue into Treatment Period 2 despite having 
achieved remission by week 16 will be known to have been on active treatment during 
Treatment Period 1. However, considering the benefit this design brings for placebo-treated 
patients with spontaneous remission and the fact that this is an early, proof-of-concept study, 
this limitation can be considered as acceptable. 
The secukinumab 300 mg every 4 weeks dosing regimen is given to subjects in the active 
treatment arm in Treatment Period 1, while the higher dosing regimen, secukinumab 300 mg 
every 2 weeks, is explored in Treatment Period 2 in subjects switching over from placebo. This 


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design enables every participating subject to receive active treatment and makes the trial 
efficient by testing the secukinumab every 4 weeks dosing regimen versus placebo, while 
additionally giving the opportunity to explore the higher dosing regimen, secukinumab 300 mg 
every 2 weeks, without having to add an additional treatment arm. 
Treatment blinding is maintained beyond the primary endpoint (week 16) throughout Treatment 
Period 2, which enables cross-comparison of the sequential efficacy and safety data of the 2-
weekly dosing regimen in Treatment Period 2 to the 4-weekly dosing regimen in Treatment 
Period 1. Furthermore, it ensures that investigators remain blinded regarding the treatment 
subjects received during Treatment Period 1. In addition, continued blinding ensures more 
objective efficacy and safety assessment during Treatment Period 2. 
An 8-week follow-up period will enable the assessment of disease activity 
 
after the end of treatment. 
The regular assessments of disease activity and clinical status ensure that safety is monitored 
closely and that both, subjects and investigators, have the opportunity to assess if the continued 
participation in the trial is to the patient´s benefit. If the subject´s participation is deemed not to 
be of benefit for the subject, she/he can exit the trial at any time. 
4.2 
Rationale for choice of background therapy 
Patients entering the trial will be allowed to use topical therapies (low-moderate potency 
corticosteroids, Over the Counter (OTC) emollients and lubricants or mouthwash for pain; 
please see Section 6.2.1 for details) as background treatment in both arms. The primary reason 
for this is to alleviate the symptom burden of subjects receiving placebo treatment during the 
first 16 weeks of the study. Especially in patients with mucosal/ oral lichen planus, symptoms 
caused by oral ulcerations may be severe and therefore symptomatic background therapy 
(topical corticosteroids, local anesthetics etc.) is important for the adequate management of 
these patients. The allowed background treatments are typically used in clinical practice to treat 
lichen 
planus 
symptoms 
(Husein-ElAhmed et al 2019; 
Tziotzios et al 2018; 
Le Cleach and Chosidow 2012) (see Section 6 for details). Although it is a key inclusion 
criterion for patients to be inadequately controlled by topical treatments, this does not mean that 
the patients do not benefit from topical treatments at all. The allowed topical treatments still 
alleviate patients´ symptoms to a certain degree and may limit further progression of the disease. 
 
 
 
 
 
 
 
 
 
 
 
 
 


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4.4 
Rationale for choice of control drugs 
In this Phase 2 trial secukinumab 300 mg every 4 weeks is compared to placebo treatment in 
Treatment Period 1. This minimizes the number of patients that need to be enrolled in the trial, 
since an active comparator would reduce the assumed difference in efficacy between the two 
treatment arms significantly and thereby increase the number of patients required to statistically 
demonstrate this difference. The number of potential active comparators for this patient 
population is highly limited and so is the clinical evidence supporting them. Currently there are 
no approved treatment options specifically for this indication. Patients enrolling in this trial 
have moderate to severe lichen planus inadequately controlled by topical therapies. In this 
"second line" setting, systemic treatments are indicated. However, there are very few systemic 
treatments having proven clinical efficacy and safety in adequately powered, randomized, 
controlled trials. Systemic corticosteroids, retinoids, cyclosporin, methotrexate or 
hydroxychloroquine are options, but often characterized by limited efficacy and safety profiles 
that are far from optimal (Thandar et al 2019). 
To minimize patients´ burden, the duration of placebo treatment is limited to 16 weeks and 
topical treatments including emollients, local anesthetics or corticosteroids of low to moderate 
potency are allowed as background therapy in both arms (see Section 6.2.1 for details). 
Although it is an inclusion criterion of this trial to be inadequately controlled by topical 


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treatments, this does not mean that patients do not derive any benefit from topical treatments. 
The allowed topical treatments while not fully curing the disease, still alleviate patients´ 
symptoms to a certain degree and may prevent further worsening of the disease that might occur 
without them. Continued topical treatment for 16 weeks is not considered a major safety risk 
for this patient population. Furthermore, randomization is done in a 2:1 ratio to reduce the 
number of patients under placebo treatment. After Week 16, all patients originally randomized 
to placebo, except those with spontaneous remission, are switched to active treatment with 
secukinumab 300 mg every 2 weeks, so all patients entering the trial receive active treatment, 
either starting at baseline or at Week 16. Since patients switching from placebo to active 
treatment are receiving secukinumab 300 mg every 2 weeks in Treatment Period 2, and patients 
who started with active treatment in Treatment Period 1 receive secukinumab 300 mg every 4 
weeks throughout both treatment periods, the cumulative dose of secukinumab each patient 
population receives differs by only 10% (3300 mg for patients initially randomized to active 
treatment vs. 3000 mg for patients initially randomized to placebo). Furthermore if the patient´s 
participation in the trial is not considered to be of benefit for the patient by the investigator or 
the patient her-/himself, or the patient requires a different therapy than the one offered in the 
trial, she/ he can exit the trial at any time. 
4.5 
Purpose and timing of interim analyses/design adaptations 
A primary endpoint analysis is planned to be conducted either once all patients have completed 
the Week 16 visit or once all patients of one of the 3 subgroups have completed the Week 16 
visit. This will be decided depending on the recruitment of the 3 cohorts. The purpose of this 
primary endpoint analysis is to assess whether secukinumab shows efficacy and safety in the 
selected lichen planus subtypes at an early time point (proof of concept). This enables planning 
of further clinical development of secukinumab in lichen planus. At the end of the study, the 
final analysis of all data collected will be performed once all patients have completed their last 
study visit. All patients, investigators and site personnel will remain blinded until final database 
lock. 
Further analyses are currently not planned. However, an unscheduled analysis could be 
conducted if a compelling reason arises, for example, if requested by health authorities. 
4.6 
Risks and benefits 
Secukinumab has demonstrated a positive benefit-risk ratio in the treatment of multiple, chronic 
inflammatory conditions including moderate to severe plaque-psoriasis, psoriatic arthritis and 
ankylosing spondylitis. Based on the currently available preclinical as well as first clinical 
evidence (case series by Solimani et al 2019), IL-17A plays a key role in the pathophysiology 
of lichen planus and secukinumab, which is directed against IL-17A, therefore has the potential 
to reduce disease activity and improve symptom severity in patients with lichen planus. 
Moreover, given the extensive exposure and the well-established and favorable safety profile 
of secukinumab in patients with moderate to severe plaque-psoriasis, Novartis is not aware of 
any medical/scientific evidence that would indicate potential differences in the safety profile of 
secukinumab between the psoriasis and the lichen planus patient populations. 
Secukinumab´s currently approved dosing (300 mg given every 4 weeks) showed a consistent 
and favorable safety profile across a large clinical development program and extensive post-


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marketing experience since its first approval for moderate to severe plaque-psoriasis in 2015. 
Approximately 4,000 patients with moderate to severe plaque-psoriasis were included in the 
studies of the registration program. This included 3,430 subjects treated with secukinumab in 
10 phase II/III studies, 2,727 of whom were treated for at least 6 months and 2,029 of whom 
were treated for at least 48 weeks. Details of the risks and benefits are outlined in the current 
version of the Investigator's Brochure. The safety data from the completed and ongoing studies 
including AE and SAE data, laboratory parameters and immunogenicity data demonstrate a 
favorable safety profile. Observed risks include infections, in particular, upper respiratory tract 
infections, neutropenia and hypersensitivity reactions that can be seen with administration of 
foreign proteins. Most of the infections were non-serious, mild to moderate in severity, 
clinically easily manageable and did not lead to treatment discontinuation. Cases of neutropenia 
were uncommon, generally mild to moderate and transient and did not lead to treatment 
discontinuation, and only a few cases were temporally associated with non-serious infections. 
Subjects with pre-existing malignancies within the past 5 years are generally excluded from 
studies with secukinumab although there is no scientific basis to suggest that secukinumab 
would increase the risk for malignancies. 
Secukinumab 300 mg s.c. given every 2 weeks is a non-approved dosing regimen currently. It 
has been administered in six completed studies in approximately 260 patients with psoriasis and 
uveitis, with approximately 120 patients receiving continuous treatment for at least 24 weeks. 
Furthermore the 300 mg every 2 weeks dosing regimen is currently being evaluated in two 
Phase 3 trials in patients with hidradenitis suppurativa (NCT03713632, NCT03713619) and in 
a Phase 3 trial in patients with moderate to severe plaque-psoriasis and a body weight ≥ 90 kg 
(NCT03504852). The safety profile observed in the data available to date is consistent with the 
known safety profile of secukinumab and no new safety concerns have been identified. 
Furthermore, secukinumab has been administered intravenously at a dose of 10 mg/kg body 
weight either short- or long-term in a number of clinical studies that enrolled patients with 
psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis or multiple sclerosis. The 
majority of patients was receiving 3 doses of 10 mg/kg i.v. over 1 month (Weeks 0, 2 and 4) 
and 38 patients with multiple sclerosis were receiving monthly 10 mg/kg i.v. doses for at least 
six months. Chronic, monthly treatment with secukinumab 10 mg/kg i.v. results in a monthly 
exposure that is approximately 2-fold higher compared to 300 mg s.c. every 2 weeks dosing 
(the bioavailability of secukinumab administered subcutaneously is 73%). No new or changed 
safety risks were observed with chronic i.v. treatment compared to the known safety profile of 
secukinumab with the approved doses. Comparisons across indications are valid given there are 
no clinically relevant differences in the pharmacokinetic profile of secukinumab observed 
between the various immune-mediated diseases studied (psoriasis, psoriatic arthritis, 
ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis, Crohn’s disease, non-infectious 
uveitis). Additional information can be found in the IB for secukinumab. 
The risk to subjects in this trial is also minimized by compliance with the eligibility criteria and 
study procedures, as well as close clinical monitoring. 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 outlined in the exclusion criteria. If there is any 
question that the subject will not reliably comply, they should not enter or continue in the study. 


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The highly bothersome symptoms of pain or severe itching (Welz-Kubiak et al 2017), the 
significant impact moderate to severe lichen planus has on patient’s quality of life including 
depression (Radwan-Oczko et al 2018; Cheng et al 2017; Welz-Kubiak et al 2017) and the 
very limited availability of effective and safe systemic treatment options for these patients 
inadequately controlled by topical treatments lead to a high degree of unmet medical need in 
the treatment of lichen planus. The established and favorable safety profile of secukinumab in 
moderate to severe plaque-psoriasis and the potential of secukinumab to reduce disease activity 
and improve symptom severity in patients with lichen planus, suggest that participation in this 
trial offers a well justifiable benefit-risk profile. 
5 
Population 
Approximately 108 subjects with biopsy-proven lichen planus will be randomized in the study 
and assigned to 3 cohorts according to their predominant lichen planus subtype (predominantly 
cutaneous lichen planus, predominantly mucosal lichen planus or lichen planopilaris).  
Each cohort will enroll 36 patients randomized in a 2:1 ratio (24 patients will enter the active 
arm, 12 patients the placebo arm). 
Drop-outs after randomization will not be replaced. 
5.1 
Inclusion criteria 
Subjects eligible for inclusion in this study must meet all of the following criteria: 
1. Written informed consent must be obtained before any assessment is performed. 
2. Female and male patients ≥ 18 years of age. 
3. Subjects must have biopsy-confirmed forms of cutaneous lichen planus (CLP), mucosal 
lichen planus (MLP), or active lichen planopilaris (LPP) eligible for systemic therapy 
based on the following criteria: 
• rated IGA of ≥ 3 at screening and baseline (moderate or severe) AND 
• inadequate response to topical corticosteroids of high-ultrahigh potency in the opinion 
of the investigator. 
4. If using any of the allowed topical treatments on the affected areas, the dose and 
application frequency should remain stable for 2 weeks prior to randomization and until 
Week 16. 
5.2 
Exclusion criteria 
Subjects meeting any of the following criteria are not eligible for inclusion in this study. 
1. Clinical history suspicious for lichenoid drug eruption. 
2. Lichen planus pigmentosus. 
3. Clinical picture or history suspicious of paraneoplastic mucosal lichen planus. 
4. Subjects whose lichen planus is a predominantly bullous variant. 
5. Mucosal LP of the oral cavity or gastrointestinal involvement requiring the patient to use 
parenteral nutrition or feeding tube. 
6. Clinical picture of scarring alopecia without active inflammation. 


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7. Clinical picture of burnt-out cicatricial alopecia (alopecia of Brocque). 
8. Patients diagnosed with frontal fibrosing alopecia (FFA) without active patches of LPP. 
9. Clinical picture of LPP in patients who have already failed 3 or more systemic 
immunosuppressive or immunomodulatory agents (e.g. systemic steroids, 
hydroxychloroquine, cyclosporine, methotrexate and mycophenolate mofetil). 
10. Currently enrolled in any other clinical trial involving any investigational agent or device. 
11. Previous exposure to any other biologic drug directly targeting IL-17A or IL-17RA (e.g. 
secukinumab, ixekizumab or brodalumab) or IL-23/p19 (e.g. tildrakizumab, guselkumab, 
risankizumab). 
12. Diagnosis of active infectious diseases of the skin, scalp or mucosa (for example bacterial, 
viral or fungal infections of the mouth) that may interfere with the assessment of the study 
disease or require treatment with prohibited medications. 
13. Diagnosis of active inflammatory diseases of the skin, scalp or mucosa other than lichen 
planus that may interfere with the assessment of the study disease or require treatment 
with prohibited medications. 
14. Presence of any other skin condition that may affect the evaluations of the study disease. 
15. Underlying conditions (including, but not limited to metabolic, hematologic, renal, 
hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal - e.g., 
Inflammatory Bowel Disease) and/or presence of laboratory abnormalities which in the 
opinion of the investigator significantly immunocompromises the subject and/or places the 
subject at unacceptable risk for receiving an immunomodulatory therapy. 
16. Current, severe, progressive or uncontrolled diseases that render the patient unsuitable for 
the trial, including any medical or psychiatric condition that, in the Investigator’s opinion, 
would preclude the participant from adhering to the protocol or completing the study per 
protocol. 
17. Ongoing use of ANY treatment prohibited by the protocol (for details, refer to Table 6-2. 
18. Plans for administration of live vaccines during the study period or within 6 weeks before 
randomization. 
19. Pregnant or nursing (lactating) women. 
20. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using methods of contraception during the entire study 
or longer if required by locally approved prescribing information (e.g. in European Union 
(EU) 20 weeks). 
Contraception methods include: 
• Total abstinence, when this is in line with the preferred and usual lifestyle of the 
patient. 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 at least six weeks before taking 
study treatment). 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). The vasectomized male 
partner should be the sole partner for that patient. 


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• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps).  
• 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 should have been stable on the same pill for a 
minimum of 3 months before taking study treatment. 
In case local regulations deviate from the contraception methods listed above, local 
regulations apply and will be described in the informed consent form (ICF). 
Note: Women are considered post-menopausal and not of childbearing potential if they 
have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical 
bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal 
ligation at least six weeks prior to enrollment. 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 childbearing potential. 
21. History of recurrent bacterial infection (at least 3 major infections resulting in 
hospitalization and/or requiring intravenous antibiotic treatment within the past 2 years). 
22. History of congenital or acquired immunodeficiency (eg, Common Variable 
Immunodeficiency [CVID]). 
23. Hepatitis B surface antigen (HBsAg) positive or Hepatitis B core antibody positive at 
screening. 
24. History of Human Immunodeficiency Virus (HIV) infection. 
25. Hepatitis C antibody positive at screening unless viral load is 0. 
26. Evidence of tuberculosis infection as defined by a positive QuantiFERON® TB-Gold test 
(QFT) at screening. Patients with a positive or indeterminate QFT test may participate in 
the study if a full tuberculosis work-up (according to local practice/guidelines) completed 
within 12 weeks prior to randomization, establishes conclusively that the patient has no 
evidence of active or latent tuberculosis. 
27. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system treated or untreated within the past 5 years, regardless of whether 
there is evidence of local recurrence or metastases (except for skin Bowen’s disease, or 
basal cell carcinoma or actinic keratosis that have been treated with no evidence of 
recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant 
colon polyps that have been removed). 
28. No additional exclusions may be applied by the investigator, in order to ensure that the 
study population will be representative of all eligible patients. 


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6 
Treatment 
6.1 
Study treatment 
The following investigational drug and comparator will be supplied and appropriately labeled 
by Novartis: 
• Investigational drug: Secukinumab 300 mg, provided as 2 s.c. injections of 1 ml prefilled 
syringe (PFS). Each 1 ml syringe contains 150 mg secukinumab. 
• Comparator: Placebo, provided as 2 s.c. injections of 1 ml prefilled syringe (PFS). 
Each placebo pre-filled syringe contains a mixture of inactive excipients, matching the 
composition and the appearance of the secukinumab 150 mg dose. 
6.1.1 
Investigational and control drugs 
Table 6-1 
Investigational and control drug 
Investigational/Co
ntrol Drug 
(Name and 
Strength) 
Pharmaceutical 
Dosage Form 
Route of 
Administration 
Supply Type 
Sponsor (global 
or local) 
Secukinumab 
150mg 
Solution for 
subcutaneous 
injection 
Subcutaneous 
injection 
Double blind 
supply, 1ml pre-
filled syringe 
Sponsor (global) 
Placebo 150mg 
Solution for 
subcutaneous 
injection 
Subcutaneous 
injection 
Double blind 
supply, 1ml pre-
filled syringe 
Sponsor (global) 
Secukinumab and the secukinumab matching placebo will be labeled as “AIN457 150 mg / 
Placebo” (1 ml) to keep the blind. Subjects will initially be instructed on how to perform the 
injection by site staff. They will also receive written instructions as to how to self-inject using 
the pre-filled syringe. 
Patients or caregivers not able/willing to self-administer the drug and perform home 
administration, will be allowed to return to the site for administration of the medication. During 
those visits, no additional assessments will be performed. 
6.1.2 
Additional study treatments 
No other treatments beyond investigational drug, placebo and allowed concomitant topical 
treatments/background treatment are included in this trial. 
6.1.3 
Treatment arms/group 
According to their diagnosis, subjects will be assigned at Screening visit to one of the following 
cohorts based on the predominant subtype of the disease (e.g. skin lesions are clinically 
dominant and the primary reason for treatment: patient is assigned to the cutaneous lichen 
planus cohort; mucosal lesions are clinically dominant and the primary reason for treatment: 
patient is assigned to the mucosal lichen planus cohort): 
• Cutaneous lichen planus 


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• Mucosal lichen planus 
• Lichen planopilaris 
Patients presenting with two concomitant subtypes of lichen planus (e.g. concomitant presence 
of skin and mucosal lesions) will be eligible to enter the trial provided the cohort assignment 
occurs following the predominant subtype. 
Within each cohort patients will be randomized to one of the treatment arms in a 2:1 ratio: 
• Cutaneous lichen planus (n=36)  
• Secukinumab 300 mg every 4 weeks (n=24) 
• Placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (n=12) 
• Mucosal lichen planus (n=36)  
• Secukinumab 300 mg every 4 weeks (n=24) 
• Placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (n=12) 
• Lichen planopilaris (n=36)  
• Secukinumab 300 mg every 4 weeks (n=24) 
• Placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (n=12) 
 Treatment is divided into 2 treatment periods: 
Treatment Period 1: Week 0-16 
• Patients in the active secukinumab 300 mg every 4 weeks treatment arm 
receive induction with secukinumab 300 mg s.c. at Weeks 0, 1, 2, 3, 4 and then 
secukinumab 300 mg s.c. every 4 weeks, meaning at Weeks 8 and 12. 
• Patients in the placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks 
treatment arm receive corresponding placebo injections s.c. at Weeks 0, 1, 2, 3, 4 and 
then every 4 weeks, meaning at Weeks 8 and 12. 
Treatment Period 2: Weeks 16-32 
• Patients in the active secukinumab 300 mg every 4 weeks treatment arm stay on 
secukinumab 300 mg every 4 weeks, meaning they receive secukinumab 300 mg s.c. at 
Weeks 16, 20, 24 and 28. In order to maintain the blinding they additionally 
receive  placebo injections at Weeks 17, 18 and 19 as well as placebo injections at Weeks 
22, 26 and 30. 
• Patients from the placebo with switch to secukinumab 300 mg every 2 weeks 
treatment arm switch over to active secukinumab 300 mg every 2 weeks treatment. They 
receive a weekly induction with secukinumab 300 mg s.c. at Weeks 16, 17, 18, 19 and 20 
and then secukinumab 300 mg every 2 weeks, meaning at Weeks 22, 24, 26, 28 and 30. 
The first injection of Treatment Period 2 is given at Week 16. The last injection (secukinumab 
300 mg or placebo) is given in both the treatment arms at week 30. 
6.1.4 
Treatment duration 
The duration of treatment is 32 weeks, with the last injection being given at Week 30. Subjects 
may be discontinued earlier from treatment due to unacceptable toxicity, disease progression, 
or at the discretion of the investigator or the subject. 


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6.2 
Other treatment(s) 
6.2.1 
Concomitant therapy 
Patients entering the trial are not allowed to use any topical therapies as background treatment 
except the ones defined in this section. Permitted topical therapies are listed below and must be 
recorded in the case report form (CRF). 
The medications listed below are allowed for use throughout the duration of the trial: subjects 
should be on a stable dose and application frequency of topical treatments 2 weeks prior 
to randomization. Administration should remain stable regarding dose and application 
frequency during Treatment Period 1 (until Week 16), and it is strongly recommended to 
maintain it at a stable level during Treatment Period 2 (from Week 16 until Week 32).  
The following topical treatments are allowed: 
• Low-moderate potency corticosteroids (Group IV, V, VI and VII as per WHO 
definition): 
Desoximetasone cream, 0.05% 
Fluocinolone acetonide ointment, 0.025% 
Fludroxycortide ointment, 0.05% 
Hydrocortisone valerate ointment, 0.2% 
Triamcinolone acetonide cream, 0.1% 
Betamethasone dipropionate lotion, 0.02% 
Betamethasone valerate cream, 0.1% 
Fluocinolone acetonide cream, 0.025% 
Fludroxycortide cream, 0.05% 
Hydrocortisone butyrate cream, 0.1%  
Hydrocortisone valerate cream, 0.2%  
Triamcinolone acetonide lotion, 0.1% 
Betamethasone valerate lotion, 0.05% 
Desonide cream, 0.05% 
Fluocinolone acetonide solution, 0.01% 
Dexamethasone sodium phosphate cream, 0.1% 
Hydrocortisone acetate cream, 1% 
Methylprednisolone acetate cream, 0.25% 
Triamcinolone acetonide oral rinse, 0.1% 
The paste formulation of a corticosteroid is considered of comparable potency to its ointment 
formulation if the concentration is the same. The gel formulation of a corticosteroid is 
considered of comparable potency to its lotion formulation if the concentration is the same.  
• OTC emollients, shampoos and lubricants for the treatment of itch and/or pain, e.g. 
anti-itch lotions containing menthol, pramoxine or antihistamines 
• (Mixed) medication for the treatment of oral pain (e.g., lubricants, OTC mouthwashes 
containing diphenhydramine, viscous lidocaine, antacid, nystatin or corticosteroids of 
Group IV, V, VI and VII as per WHO definition) 


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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 
randomizing a subject or allowing a new medication to be started. If the subject is already 
enrolled, contact Novartis to determine if the subject should continue participation in the study. 
All other forms of topical treatments for any of the 3 LP subtypes are not allowed during the 
Screening and Treatment periods. All medications, procedures, and significant non-drug 
therapies (including physical therapy and blood transfusions) administered after the subject was 
enrolled in the study must be recorded on the appropriate CRFs.  
6.2.2 
Prohibited medication 
Use of any treatments displayed in the table below that could confound the efficacy assessment 
of the investigational drug is NOT allowed during the course of the study for ANY indication. 
All prohibited treatments should be washed out as shown in the table below. The investigator 
should instruct the subject to notify the study site about any new treatments. At the discretion 
of the investigator, if any use of a prohibited treatment presents an undue safety risk for the 
subject, the study treatment must be discontinued. If a live vaccination has to be administered, 
the study treatment must be discontinued. If a prohibited treatment is used during the study, the 
subject should discontinue the use of the prohibited treatment if he/she wishes to continue in 
the study. In case of undue safety risk for the subject, the subject should discontinue study 
treatment at the discretion of the investigator. 
Table 6-2 
Prohibited medication 
Medication 
Washout period before 
randomization 
Note 
Ustekinumab 
24 weeks 
  
Etanercept 
4 weeks 
  
Biological agents targeting IL-
17A or IL-17RA (e.g. 
ixekizumab, brodalumab) 
No prior use allowed 
  
Biological agents targeting IL-
23/p19 (e.g. guselkumab, 
risankizumab, tildrakizumab) 
No prior use allowed 
  
Systemic, biological 
immunomodulating agents 
other than above (e.g. agents 
directed against TNFα such as 
adalimumab, infliximab, 
certolizumab) 
12 weeks 
  


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Medication 
Washout period before 
randomization 
Note 
Systemic, non-biological 
immunomodulating treatments 
(e.g. methotrexate, apremilast, 
systemic corticosteroids, 
cyclosporine, 
cyclophosphamide, 
sulphasalazine, azathioprin, 
mycophenolate mofetil, 
dapsone, hydroxychloroquine) 
4 weeks 
  
Finasteride, dutasteride 
4 weeks 
  
PPARγ agonists (e.g. 
pioglitazone), naltrexone, 
doxycycline 
4 weeks 
  
Systemic use of griseofulvin or 
itraconazole 
4 weeks 
  
Retinoids 
4 weeks 
  
Low-level light therapy 
4 weeks 
  
Phototherapy (e.g. UVB) 
4 weeks 
  
Photochemotherapy (e.g. 
psoralen and UVA (PUVA)) 
4 weeks 
  
Topical calcineurin inhibitors 
(cyclosporin, tacrolimus, 
pimecrolimus) or topical vitamin 
D analogues 
4 weeks 
  
Topical corticosteroids of high 
- ultrahigh potency (group I, 
II, III as per WHO definition)  
4 weeks 
If patients require topical 
corticosteroids, they have to be 
switched to the low - moderate 
potency corticosteroids (group 
IV, V, VI and VII per WHO 
definition) given in 
Section 6.2.1. Subjects should 
be on a stable dose and 
application frequency of the low 
- medium potency 
corticosteroids 2 weeks prior to 
randomization. Administration 
should remain stable regarding 
dose and application frequency 
during Treatment Period 1 
(until Week 16), and it is 
strongly recommended to 
maintain it at a stable level 
during Treatment Period 2 
(from Week 16 until Week 32).  
Topical phosphodiesterase 4 
inhibitors (e.g. crisaborole) 
4 weeks 
  
Intralesional corticosteroid 
injection 
4 weeks 
  
Depot corticosteroid injection 
6 weeks 
 


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Medication 
Washout period before 
randomization 
Note 
Live virus vaccinations 
6 weeks 
  
Any investigational treatment or 
participation in any 
interventional trial 
4 weeks or 5 half-lives, 
whichever is longer 
  
6.2.3 
Rescue medication 
Use of rescue medication is not permitted in this study. Regarding the use of topical 
corticosteroids during the study, please see previous (section 6.2.1 and section 6.2.2). 
6.3 
Subject numbering, treatment assignment, randomization 
6.3.1 
Subject numbering 
Each subject is identified in the study by a Subject Number (Subject No.), that is assigned when 
the subject is first enrolled for screening and is retained as the primary identifier for the subject 
throughout his/her entire participation in the trial. The Subject No. consists of the Center 
Number (Center No., as assigned by Novartis to the investigative site) with a sequential subject 
number suffixed to it, so that each subject is numbered uniquely across the entire database. 
Upon signing the informed consent form, the subject is assigned to the next sequential Subject 
No. available. 
The investigator or his/her staff will contact the interactive recording technology (IRT) and 
provide the requested identifying information for the subject to register them into the IRT. 
If the subject fails to be treated for any reason, the IRT must be notified within 2 days that the 
subject was not treated. The reason for not being treated will be entered on the appropriate 
eCRF. 
6.3.2 
Treatment assignment, randomization 
At the baseline visit, all eligible subjects will be randomized via Interactive Response 
Technology (IRT) to one of the treatment arms. The investigator or his/her delegate will contact 
the IRT after confirming that the subject fulfills all the inclusion/exclusion criteria. The IRT 
will assign a randomization number to the subject, which will be used to link the subject to a 
treatment arm and will specify a unique medication number for the first package of study 
treatment to be dispensed to the subject. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from subjects and investigator staff. A subject 
randomization list will be produced by the IRT provider using a validated system that automates 
the random assignment of subject numbers to randomization numbers. These randomization 
numbers are linked to the different treatment arms, which in turn are linked to medication 
numbers. 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 random assignment 
of medication numbers to packs containing the study treatment. 
All efficacy and safety assessments should be done prior to calling IRT. 


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The randomization scheme for subjects will be reviewed and approved by a member of the 
Randomization Office. 
6.4 
Treatment blinding 
This is a double blind study. Subjects, investigator staff, persons performing the assessments, 
and clinical trial team (CTT) will remain blind to the identity of the treatment from the time of 
randomization until database lock, using the following methods: 
(1) Randomization data are kept strictly confidential until the time of unblinding and will not 
be accessible by anyone else involved in the study with the following exceptions: 
• Specific members whose role in trial conduct requires their unblinding (e.g., IRT, 
designated Unblinded Data manager (if needed)) 
• Global Clinical Supply 
• Designated Novartis study team members involved in the primary endpoint analysis 
(2) the identity of the treatments will be concealed by the use of study treatments that are all 
identical in packaging, labeling, schedule of administration, appearance, taste, and odor. 
 
 
 
Unblinding will occur in the case of subject emergencies and at the conclusion of the study. 
6.5 
Dose escalation and dose modification 
Study treatment dose adjustments are not allowed and interruptions are not permitted except as 
described in Section 6.5.1. 
6.5.1 
Dose modifications 
Study treatment interruption is only permitted if, in the opinion of the investigator, a subject 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. These changes must be recorded on the appropriate eCRF. 
6.5.2 
Follow-up for toxicities 
There is no protocol-guided follow-up for toxicities. Safety monitoring and reporting for AEs 
and SAEs is described in Section 10. 
6.6 
Additional treatment guidance 
6.6.1 
Treatment compliance 
All doses of study treatment administration will be recorded on the appropriate Dosage 
Administration Record eCRF page (visit specific and summary pages). For study treatment 
administration at home, the investigator must promote compliance by instructing the subject to 
administer the study treatment exactly as instructed and by stating that compliance is necessary 


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for the subject’s safety and the validity of the study. The subject must also be instructed to 
contact the investigator if he/she is unable for any reason to administer the study treatment.  
All study treatment dispensed and returned must be recorded in the Drug Accountability Log. 
Compliance will also be assessed and confirmed by a field monitor by drug accountability logs, 
by documentation and information provided by IRT and by the qualified site personnel that are 
responsible for treatment dispensation, administration and accountability. Cross-checks should 
be performed for home administrations (H) and empty medication outer packing and subject's 
returned PFS should be collected for compliance checks by field monitors. This information 
should be captured in the source document at each visit.  
 
 
6.6.2 
Recommended treatment of adverse events 
Treatment for adverse events should follow general guidelines for standard-of-care and is at the 
discretion of the investigator or treating physician. There are no specific treatment 
recommendations for adverse events that may possibly occur in this trial. Refer to the 
Investigator's Brochure for adverse events related to secukinumab. 
Medication used to treat adverse events (AEs) must be recorded on the appropriate CRF. 
6.6.3 
Emergency breaking of assigned treatment code 
Emergency code breaks must only be undertaken when it is required to in order to treat the 
subject safely. Most often, study treatment discontinuation and knowledge of the possible 
treatment assignments are sufficient to treat a study subject who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the 
investigator contacts the system to break a treatment code for a subject, he/she must provide the 
requested subject identifying information and confirm the necessity to break the treatment code 
for the subject. The investigator will then receive details of the investigational drug treatment 
for the specified subject and a fax or email confirming this information. The system will 
automatically inform the Novartis monitor for the site and the study team that the code has been 
broken. 
It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT/code break cards at any time in case of emergency. The investigator 
will provide: 
• protocol number 
• study drug name 
• subject number 
In addition, oral and written information must be provided to the subject on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that un-blinding 
can be performed at any time. 
Study drug must be discontinued after emergency unblinding. 


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The appropriate personnel from the study site and Novartis will assess whether study treatment 
should be discontinued for any subjects whose treatment code has been broken inadvertently 
for any reason. 
6.7 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described under the 
investigational and control drugs section. A unique medication number is printed on the study 
medication label. 
Investigator staff will identify the study medication kits to dispense to the subject 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 subject, site 
personnel will detach the outer part of the label from the packaging and affix it to the source 
document. 
In the event of a major health care disruption (e.g., pandemic, epidemic) that limits or prevents 
on-site study visits, study drug may be shipped or provided directly to patients for home 
administration if needed. The shipment/provisioning will be for a maximum quantity covering 
a 4-month supply. In this case, regular phone calls (every 4 weeks or more frequently, if needed) 
will occur between the site and the patient for instructional purposes, safety monitoring and 
discussion of the patient´s health status until the patient can again visit the site.  
6.7.1 
Handling of study treatment and additional treatment 
6.7.1.1 
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 and in the Investigator’s Brochure. 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 subject except for the medication number. 
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 
monitors during site visits or remotely and at the completion of the trial. Subjects will be asked 
to return all unused study treatment and packaging at the end of the study or at the time of 
discontinuation of study treatment. 
At the conclusion of the study, and as appropriate during the course of the study, 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. 


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6.7.1.2 
Handling of additional treatment 
Not applicable 
6.7.2 
Instruction for prescribing and taking study treatment 
Secukinumab solution for s.c. injection or placebo secukinumab solution (active or placebo, 
respectively) will be provided in pre-filled syringes (PFS). 
Each subject will receive one box per visit throughout the study. Each box will contain: 
• two 1ml PFS of secukinumab 150 mg OR 
• two 1ml PFS of secukinumab/placebo 150 mg 
All study treatment kits assigned to the subject by IRT during the study will be captured in the 
IRT system. 
The first study treatment administration will occur at the baseline/randomization visit after the 
inclusion/exclusion criteria have been confirmed and all scheduled study assessments have been 
performed. All study assessments, including completion of Patient Reported Outcomes (PROs) 
and blood withdrawal, should be completed prior to the self-injection of study treatment. 
All doses of study treatment (secukinumab and/or placebo) will be self-administered by the 
subject/ trained caregiver either at the study site after the study assessments for the visits have 
been completed or at home. 
The first use at baseline and the Week 1 assessments of the self-injection will take place in the 
context of an observed assessment under the supervision of one site staff member. At the 
baseline visit, subjects will be instructed by the site staff on how to self-inject via the pre-filled 
syringe (Instructions for Use (IFU) containing detailed information about self-administration of 
study treatment should be provided to each subject at the beginning of the study). After 
providing detailed explanations/instructions, subjects will then be asked to raise any questions. 
Thereafter, they will proceed with self-injection.  
Home administrations (H) should be done at pre-defined visits (see Section 3). Home 
administration can be performed by the subject or trained caregiver. If the subject or caregiver 
is not able/confident to perform home administration, the subject will be allowed to return to 
the site for administration of the medication. However, during those visits no additional 
assessments will be required.  
In case of a major health care disruption (e.g., pandemic, epidemic) that limits or prevents 
on-site study visits, home administration of the study drug is generally permitted. Home 
administration can be performed by the patient or a trained caregiver. Study participants or 
caregivers will be trained adequately on how to perform administrations of the study treatment, 
if not already trained. If the patient or caregiver is not trained for drug administration and cannot 
visit the site to undergo training, the site can consider providing suitable virtual training and 
oversight. A joint decision together with the patient or caregiver should be made as to whether 
this constitutes sufficient training and oversight.  
During home administrations, subjects will be instructed to contact the investigator/site staff in 
case they are experiencing any AE/SAEs or have any concerns. 
Administration 


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The study treatment solution must be injected in non-affected areas of the skin. 
Pre-filled syringes should be kept at 2 to 8°C (36°F and 46°F), never be frozen, and should be 
protected from light. Prior to administration, the boxes containing the pre-filled syringes should 
be allowed to adapt to room temperature unopened for about 20 minutes before administration. 
Used PFS (if according to the regulatory needs of the respective countries) should be stored in 
the original boxes and returned at the next site visit for reconciliation 
All kits of study treatment assigned by the IRT will be recorded in the IRT system. 
7 
Informed consent procedures 
Eligible subjects may only be included in the study after providing (witnessed, where required 
by law or regulation), IRB/IEC-approved informed consent. 
If applicable, in cases where the subject's representative(s) gives consent (if allowed according 
to local requirements), the subject must be informed about the study to the extent possible given 
his/her understanding. If the subject 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 subject source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent form 
that complies with the ICH 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 previously known common side effects of the investigational drug can be 
found in the Investigator's Brochure (IB). This information will be included in the subject 
informed consent and should be discussed with the subject 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 subject. 
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 agree that, in order 
to participate in the study, they must adhere to the contraception requirements. 
 
 
 
 
 
Declining to participate in these optional assessments will in no way affect the subject’s ability 
to participate in the main research study. 
A copy of the approved version of all consent forms must be provided to Novartis/sponsor after 
IRB/IEC approval. 


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8 
Visit schedule and assessments 
The assessment schedule (Table 8-1) lists all of the assessments and details when they are 
performed. All data obtained from these assessments must be supported in the subject’s source 
documentation. 
Subjects should be seen for all visits on the designated day or as close as possible to the original 
planned visit schedule. Missed or rescheduled visits should not lead to automatic 
discontinuation.   
During the treatment periods, subjects may be seen at unscheduled visits, e.g., if they experience 
deterioration of lichen planus, or AEs that in the opinion of the investigator need intervention, 
or repeated laboratory testing. The assessment(s) performed at an unscheduled visit are at the 
investigator’s discretion. 
In the event of a major health care disruption (e.g., pandemic, epidemic) that limits or prevents 
on site study visits, regular phone calls (every 4 weeks or more frequently, if needed) will occur 
until the subject can again visit the site. Events qualifying for being reported in the CRF (e.g., 
AE, procedure) should be entered as appropriate.  Special effort should be made to collect 
information related to EOT or End of study visits. If it is not feasible to conduct the EOT or the 
Week 40 visit on-site, phone calls should be attempted instead. 
Subjects who prematurely discontinue study treatment for any other reason than withdrawal of 
informed consent should not be considered as discontinued from the study, see Section 9.1.  
Special effort should be made to ensure that patients who prematurely discontinue study 
treatment during Treatment Period 1 attend all scheduled visits until including the Week 
16 visit.  
Assessments should be completed in the following order: 
1. Patient reported outcomes (e.g. DLQI). 
2. Physician reported assessments (e.g. IGA, REU): IGA should be done first, before 
applying the other physician reported assessments (e.g. REU or LPPAI). 
3. Study visit procedures (e.g. vital signs measurements, laboratory and 
 
 biopsy procedures). 
 
 


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Table 8-1 
Assessment Schedule 
Period Screening 
Treatment Period 1 
Notes 
Visit Name Screening Baseline Week 1 Week 2 
Week 3 
Week 4 Week 8 Week 12 Week 16 
EOT1 
Visit Numbers1 
1 
20 
100 
110 
120 
130 
140 
150 
160 
 
Days 
-28 to -1 
1 
8 
15 
22 
29 
57 
85 
113 
Last 
dose + 4 
weeks 
Informed consent 
X 
  
  
  
  
  
  
  
    
 
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 
3 For all patients in the CLP 
cohort. Additionally for patients 
in the MLP cohort who have a 
concomitant cutaneous 
affection. 
4 For all patients in the MLP 
cohort who have an oral 
affection of the disease. 
Additionally for patients in the 
CLP cohort who have a 
concomitant oral affection. 
5 For all patients in the LPP 
cohort. 
6 For all patients in the MLP 
cohort who have an oral 
affection of the disease. 
Demography 
X 
  
  
  
  
  
  
  
 
 
Inclusion / Exclusion criteria 
X 
X 
  
  
  
  
  
  
 
 
Smoking history 
X 
  
  
  
  
  
  
  
 
 
Lichen planus medical 
history 
X 
  
  
  
  
  
  
  
 
 
Previous lichen planus 
therapies 
X 
  
  
  
  
  
  
  
 
 
Other medical history 
X 
  
  
  
  
  
  
  
 
 
Prior medications 
X 
  
  
  
  
  
  
  
 
 
Concomitant medications 
update as necessary 
Prior or concomitant non-
drug therapies/procedures 
update as necessary 
Adverse Events 
update as necessary 
Vital Signs 
X 
X 
  
  
  
  
X 
  
X 
X 
Body Height 
X 
  
  
  
  
  
  
  
 
 
Body Weight 
X 
X 
  
  
  
X 
X 
X 
X 
X 
Physical examination 
S 
S 
  
  
  
  
  
  
 
 
Hepatitis screen 
X 
  
  
  
  
  
  
  
 
 
Tuberculosis test 
S 
  
  
  
  
  
  
  
 
 
Investigator's Global 
Assessment (IGA) 
X 
X 
  
X 
  
X 
X 
X 
X 
X 


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Period Screening 
Treatment Period 1 
Notes 
Visit Name Screening Baseline Week 1 Week 2 
Week 3 
Week 4 Week 8 Week 12 Week 16 
EOT1 
Visit Numbers1 
1 
20 
100 
110 
120 
130 
140 
150 
160 
 
Days 
-28 to -1 
1 
8 
15 
22 
29 
57 
85 
113 
Last 
dose + 4 
weeks 
Physician´s assessment of 
surface area of disease 
(PSAD)3 
 
X 
  
X 
  
X 
X 
X 
X 
X 
7 Not to be done if EOT 
already happened 
8 For all patients in the CLP 
cohort. 
9 For all patients in the MLP 
cohort. 
10 Optional 
11 Historical biopsies are 
accepted IF THEY ARE NOT 
OLDER THAN 3 MONTHS 
BEFORE SCREENING VISIT 
and if the investigator is able to 
provide the stained slides to 
the central lab for digitalization. 
Reticular Erythematous 
Ulcerative (REU) score4 
  
X 
  
X 
  
X 
X 
X 
X 
X 
Lichen Planopilaris Activity 
Index (LPPAI)5 
  
X 
  
  
  
  
X 
  
X 
X 
Oral Lichen planus symptom 
severity measure (OLPSSM)6 
  
X 
  
X 
  
X 
X 
X 
X 
X 
SCALPDEX5 
  
X 
  
  
  
X 
X 
X 
X 
X 
DLQI 
  
X 
  
  
  
X 
X 
X 
X 
X 
Patient assessment of itch 
  
X 
  
X 
  
X 
X 
X 
X 
X 
Patient assessment of pain 
  
X 
  
X 
  
X 
X 
X 
X 
X 
Hematology 
X 
X 
  
  
  
  
X 
  
X 
X 
Clinical chemistry 
X 
X 
  
  
  
  
X 
  
X 
X 
Urine pregnancy test (local) 
S 
S 
  
  
  
  
  
  
S7 
S 
Pregnancy test (serum) 
X 
  
  
  
  
  
  
  
 
 


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Period Screening 
Treatment Period 1 
Notes 
Visit Name Screening Baseline Week 1 Week 2 
Week 3 
Week 4 Week 8 Week 12 Week 16 
EOT1 
Visit Numbers1 
1 
20 
100 
110 
120 
130 
140 
150 
160 
 
Days 
-28 to -1 
1 
8 
15 
22 
29 
57 
85 
113 
Last 
dose + 4 
weeks 
Skin biopsy8 
X11 
  
Mucosal biopsy9 
X11 
  
Scalp biopsy5 
X11 
  
Contact IRT 
S 
S 
S7 
S7 
S7 
S7 
S7 
S7 
S7 
S 
Drug administration 
  
X 
X7 
X7 
X7 
X7 
X7 
X7 
X7 
 
 
 


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Period 
Treatment Period 2 
Notes 
Visit Name Week 
17 
Week 
18 
Week 
19 
Week 
20 
Week 
22 
Week 
24 
Week 
26 
Week 
28 
Week 
30  
Week 
32 
EOT2 
Visit Numbers1 
170 
180 
190 
200 
210 
220 
230 
240 
250 
1999 
 
Days 
120 
127 
134 
141 
155 
169 
183 
197 
211 
225 
Last 
dose + 2 
weeks 
Concomitant medications2 
update as necessary 
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 During home 
administrations, adverse 
events that may occur as well 
as concomitant medication 
should be collected by the 
investigator and reported in the 
eCRF 
3 For all patients in the CLP 
cohort. Additionally for patients 
in the MLP cohort who have a 
concomitant cutaneous 
affection. 
4 For all patients in the MLP 
cohort who have an oral 
affection of the disease. 
Additionally for patients in the 
CLP cohort who have a 
concomitant oral affection. 
Prior or concomitant non-
drug therapies/procedures 
update as necessary 
Adverse Events2 
update as necessary 
Vital Signs 
  
  
  
  
  
X 
  
  
  
X 
X 
Body Weight 
  
  
  
X 
  
X 
  
X 
  
X 
X 
Physical examination 
  
  
  
  
  
  
  
  
  
S7 
S 
Investigator's Global 
Assessment (IGA) 
  
  
  
X 
  
X 
  
X 
  
X 
X 
Physician´s assessment of 
surface area of disease 
(PSAD)3 
  
  
  
X 
  
X 
  
X 
  
X 
X 
Reticular Erythematous 
Ulcerative (REU) score4 
  
  
  
X 
  
X 
  
X 
  
X 
X 
Lichen Planopilaris Activity 
Index (LPPAI)5 
  
  
  
  
  
X 
  
  
  
X 
X 
Oral Lichen planus symptom 
severity measure (OLPSSM)6 
  
  
  
X 
  
X 
  
X 
  
X 
X 
SCALPDEX5 
  
  
  
X 
  
X 
  
X 
  
X 
X 
DLQI 
  
  
  
X 
  
X 
  
X 
  
X 
X 
Patient assessment of itch 
  
  
  
X 
  
X 
  
X 
  
X 
X 
Patient assessment of pain 
  
  
  
X 
  
X 
  
X 
  
X 
X 


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Period 
Treatment Period 2 
Notes 
Visit Name Week 
17 
Week 
18 
Week 
19 
Week 
20 
Week 
22 
Week 
24 
Week 
26 
Week 
28 
Week 
30  
Week 
32 
EOT2 
Visit Numbers1 
170 
180 
190 
200 
210 
220 
230 
240 
250 
1999 
 
Days 
120 
127 
134 
141 
155 
169 
183 
197 
211 
225 
Last 
dose + 2 
weeks 
5 For all patients in the LPP 
cohort. 
6 For all patients in the MLP 
cohort who have an oral 
affection of the disease. 
7 Not to be done if EOT 
already happened.  
8 For all patients in the CLP 
cohort. 
9 For all patients in the MLP 
cohort. 
 
12 These injections will be 
self-administered at home by 
the patient, unless a preference 
for office-administration is 
expressed 
Hematology 
  
  
  
  
  
X 
  
  
  
X 
X 
Clinical chemistry 
  
  
  
  
  
X 
  
  
  
X 
X 
Urine pregnancy test (local) 
  
  
  
  
  
  
  
  
  
S7 
S 
Pregnancy test (serum) 
  
  
  
  
  
  
  
  
  
  
 
Skin biopsy8 
  
  
  
  
  
  
  
  
  
  
 
Mucosal biopsy9 
  
  
  
  
  
  
  
  
  
  
 
Scalp biopsy5 
  
  
  
  
  
  
  
  
  
X7 
X 
Contact IRT 
  
  
  
S7 
  
S7 
  
S7 
  
S7 
S 
Drug administration 
  
  
  
X7 
  
X7 
  
X7 
  
  
 
Home administration12 
X7 
X7 
X7 
  
X7 
  
X7 
  
X7 
  
 
 
 
 


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Period 
Follow-up  
Unplanned 
Notes 
Visit Name 
Week 36 
Week 40 
Unscheduled13 
Visit Numbers1 
 
 
260 
Days 
253 
281 
- 
Concomitant medications 
update as necessary 
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 
3 For all patients in the CLP cohort. Additionally for patients in the MLP 
cohort who have a concomitant cutaneous affection. 
4 For all patients in the MLP cohort who have an oral affection of the 
disease. Additionally for patients in the CLP cohort who have a 
concomitant oral affection. 
5 For all patients in the LPP cohort. 
6 For all patients in the MLP cohort who have an oral affection of the 
disease. 
8 For all patients in the CLP cohort. 
9 For all patients in the MLP cohort. 
13 The assessments performed at an unscheduled visit are at the 
discretion of the investigator 
Prior or concomitant non-
drug therapies/procedures 
update as necessary 
Adverse Events 
update as necessary 
Vital Signs 
  
X 
X 
Body Height 
  
  
  
Body Weight 
  
X 
X 
Physical Examination 
  
  
S 
Hepatitis screen 
  
  
  
Tuberculosis test 
  
  
S 
Investigator's Global 
Assessment (IGA) 
X 
X 
X 
Physician´s assessment of 
surface area of disease 
(PSAD)3 
X 
X 
X 
Reticular Erythematous 
Ulcerative (REU) score4 
X 
X 
X 
Lichen Planopilaris Activity 
Index (LPPAI)5 
  
X 
X 
Oral Lichen planus symptom 
severity measure 
(OLPSSM)6 
X 
X 
  
SCALPDEX5 
X 
X 
  
DLQI 
X 
X 
  
Patient assessment of itch 
X 
X 
X 
Patient assessment of pain 
X 
X 
X 


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Period 
Follow-up  
Unplanned 
Notes 
Visit Name 
Week 36 
Week 40 
Unscheduled13 
Visit Numbers1 
 
 
260 
Days 
253 
281 
- 
Hematology 
  
X 
X 
Clinical Chemistry 
  
X 
X 
urine pregnancy test (local) 
  
  
S 
Pregnancy Test (serum) 
  
  
X 
Skin biopsy8 
  
  
  
Mucosal biopsy9 
  
  
  
Scalp biopsy5 
  
  
  
Contact IRT 
  
  
  
 
 
 
 
 
 


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8.1 
Screening 
If for any reason the subject is a screen failure, the subject may be rescreened once only. If a 
subject rescreens for the study, then the subject must sign a new ICF and be issued a new 
subject number prior to any screening assessment being conducted for the subject under the 
new screening subject number. Patients may also be rescreened at a later time if site closures or 
other logistical issues prevent randomization as planned. Patients presenting with a reduction 
in the IGA score between screening and baseline, with the IGA not qualifying as moderate or 
severe at the baseline visit (i.e., IGA score of 2, 1 or 0), will not be eligible for re-screening. 
For all rescreened subjects, the investigator/qualified site staff will record if the subject was 
rescreened on the rescreening eCRF and the original screening number the subject was issued 
prior to the current screening number. 
Informed Consent for a rescreened subject must be obtained prior to performing any study-
related assessment or collecting any data for the Screening Visit. For rescreening, all screening 
assessments must be performed as per protocol, except for the tuberculosis (TB) work up, if 
applicable, if performed not more than 12 weeks before randomization. However, the subject 
must repeat the QuantiFERON-TB Gold assay performed by the central laboratory. 
Information to be collected on screening failures 
Subjects who sign an informed consent form and subsequently found to be ineligible prior to 
randomization will be considered a screen failure. The reason for screen failure should be 
recorded on the appropriate CRF. The demographic information, informed consent, and 
Inclusion/Exclusion pages must also be completed for screen failure subjects. No other data 
will be entered into the clinical database for subjects who are screen failures, unless the subject 
experienced a serious adverse event during the screening phase (Section 10.1.3, SAE reporting). 
Adverse events that are not SAEs will be followed up by the investigator and collected only in 
the source data. If the subject fails to be randomized, the IRT must be notified within 2 days of 
the screen fail that the subject was not randomized. 
8.2 
Subject demographics/other baseline characteristics 
Country-specific regulations should be considered for the collection of demographic and 
baseline characteristics in alignment with the CRF. 
8.2.1 
Demography 
Subjects demographics data will include: age, gender, race and ethnicity. 
8.2.2 
Prior Lichen Planus medical history and previous therapies 
The following information should be collected and entered in the relevant CRF page: 
• lichen planus subtype: Cutaneous lichen planus, mucosal lichen planus, lichen 
planopilaris (note that the predominant subtype as well as potential concurrent subtypes, if 
present, are collected) .  
• date of first symptoms 
• date of first diagnosis of lichen planus 


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• any treatments for lichen planus since initial diagnosis prior to study entry will be 
collected and recorded in the eCRF along with the duration of the prior therapy and reason 
for discontinuation. 
8.2.3 
Smoking history 
The current and/or previous tobacco use will be recorded prior to randomization, as well as the 
estimated number of pack-years based on the approximate consumption per year. Use of e-
cigarettes will be recorded in the Medical history CRF. 
8.2.4 
Medical history/current medical conditions 
Relevant medical history and current medical conditions includes data prior to signing of the 
informed consent and should be recorded in the Medical History eCRF. Whenever possible, 
diagnoses and not symptoms should be recorded. 
Significant findings that are observed after the subject has signed the ICF and that meet the 
definition of an AE must be recorded in the AE eCRF. 
8.2.5 
Prior and concomitant medications 
Concomitant medications and prior medications taken over the 6 months preceding study 
enrollment for reasons other than lichen planus will be captured at the screening visit, and 
updated as necessary in the relevant eCRF.  
8.2.6 
Determination of the tuberculosis status 
Determination of tuberculosis (TB) status should be done at Screening and should be performed 
as defined by local guidelines. The TB status must be determined by medical history, signs, 
symptoms, and TB testing (QuantiFERON-TB Gold assay). Any significant findings should be 
recorded in the eCRF  (Section 15.3) for more details. 
8.3 
Efficacy 
The following section describes the efficacy measures applied in this study. Whenever possible 
the following assessments should be performed by the same evaluator throughout the study. 
8.3.1 
Investigator’s Global Assessment (IGA) 
The IGA grading should be done first, before performing any other physician assessments 
(e.g. REU, LPPAI, etc). Whenever possible, the IGA assessment should be performed by the 
same evaluator throughout the study. 
The IGA table (Table 8-2) will provide a harmonized, 5-point grading system to assess disease 
severity for patients of all 3 subtypes entering the study. 
The predominant subtype defines the IGA score of the patient.  
The IGA grading is based on the predominant subtype alone, meaning on the subtype of 
the cohort the patient is in. In addition, the IGA score is also collected separately for 
concomitant subtypes, if present. 
 
 


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Table 8-2 
Investigator's Global Assessment grading 
IGA score 
Cutaneous Lichen 
Planus 
Mucosal Lichen 
Planus 
Lichen Planopilaris 
0 - Clear 
No disease. Possible 
flat, hyperpigmented 
lesions. 
No disease. 
No active disease. 
Hypopigmented, 
cicatricial patches. Pull 
test negative. 
1 - Minimal 
Barely palpable (<0.5 
mm), scattered 
papules, mild 
erythema. 
Typically associated 
with minimal pruritus. 
Reticular, white, patch-
type striations 
involving any oral or 
genital mucosal site(s) 
(“Wickham Striae”). 
Absence of ulcers. 
Typically associated 
with no symptoms. 
Predominantly inactive 
disease 
(hypopigmented 
cicatricial patches). 
Absence of disease 
spreading. Pull test 
negative. Minimal 
scalp erythema and/or 
perifollicular erythema 
without scale. 
Typically associated 
with minimal pruritus. 
2 - Mild 
Moderately elevated 
papules (<1 mm) 
and/or small plaques 
(<2 cm2). Involvement 
of limited areas, 
erythema. 
Typically associated 
with mild pruritus. 
Plaque-type, mucosal 
lichen planus involving 
any oral or genital 
mucosal site(s). 
Absence of ulcers or 
presence of one focal 
ulceration (<0.5 cm2). 
Typically associated 
with mild pain or 
sensitivity. 
Rare perifollicular 
erythema, rare 
perifollicular 
hyperkeratosis and 
interfollicular scale. 
Stable or slowly 
spreading disease. 
Pull test negative. 
Typically associated 
with mild pruritus. 
3 - Moderate 
Thick, elevated (<2 
mm), hypertrophic, 
violaceous papules or 
presence of non-
hypertrophic, plaque-
like disease (>2 cm2), 
either generalized or 
involving specific 
areas or specific 
locations (e.g. face, 
neck). Red/violaceous 
erythema, possible 
scales. 
Typically associated 
with moderate pruritus. 
Desquamative 
gingivitis or vulvitis. 
Presence of unilateral 
or bilateral ulcerations 
involving any oral or 
genital mucosal site(s). 
Overall area affected 
by ulceration should 
be <2 cm2. 
Typically associated 
with moderate pain 
and sensitivity. 
Hairless patches with 
perifollicular and 
interfollicular 
erythema, follicular 
hyperkeratosis and 
interfollicular scaling. 
Active spreading 
disease. Pull test 
positive for telogen 
hairs. 
Typically associated 
with moderate pruritus, 
pain and/or burning. 


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4 - Severe 
Generalized, papular 
or plaque-type, 
elevated lesions (>2 
mm) OR localized 
hypertrophic lesions 
(>2 cm2). Marked 
red/violaceous 
erythema. Possible 
scales, blisters and 
ulcers. 
Typically associated 
with severe pruritus. 
Presence of bilateral 
or extensive unilateral 
ulcers involving any 
oral or genital mucosal 
site(s). Overall area 
affected by ulceration 
should be >2 cm2. 
Possible esophageal 
involvement 
(established by 
endoscopy). 
Typically associated 
with severe pain and 
sensitivity. 
Hairless patches with 
perifollicular and 
interfollicular, intense 
erythema, extensive 
perifollicular and 
interfollicular scaling. 
Crusting, pustules. 
Active spreading 
disease. Pull test 
positive for telogen or 
anagen hairs. 
Typically associated 
with severe pruritus, 
pain and/or burning. 
The grading should be mainly driven by the lesion characteristics. Symptoms, such as pain 
or pruritus, may or may not be associated. 
8.3.2 
Physician´s assessment of surface area of disease (PSAD) 
The Physician Assessment of Surface Area of Disease (PSAD) evaluates the extent of cutaneous 
lesions. Since no validated scales are available to quantify the area of disease in CLP, the present 
study will utilize the PSAD grading score as previously reported in the only randomized trial 
conducted with a biologic therapy in CLP (etanercept, NCT00285779). 
The PSAD will be estimated by the investigator/trained qualified designee from the percentages 
of areas affected, including head, trunk, upper limbs and lower limbs. Whenever possible, the 
same assessor should perform the PSAD assessment at all visits. The assessor will report the 
percentage of the surface area involved with disease using a Likert scale.  
Assessment scores range from 0-5, with lower scores corresponding to lower percentages of 
surface area with disease. 
0: clear 
1: <2% of the total body surface area. Small, localized papules 
2: 2-9% of the total body surface area. Lesions affecting limited areas (e.g. wrists or ankles) 
3: 10-29% of the total body surface area. Lesions affecting extensive areas (e.g. upper limbs or 
back) 
4: 30-50% of the total body surface area. Lesions affecting extensive areas or in multiple 
locations (e.g. trunk and lower/upper limbs) 
5: >50% of the total body surface area. Generalized involvement  
As reference, the percentages utilized for the Body Surface Area (BSA) assessment should be 
considered (head=10%, trunk=30%, upper limbs=20%, lower limbs=40%). 
Post-inflammatory hyperpigmentation should NOT be considered as surface area affected 
by the disease. 


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The PSAD assessment is required for all subjects enrolled in the CLP cohort. In addition, the 
PSAD assessment is required for subjects enrolled in the MLP cohort in case they have a 
concomitant cutaneous involvement. 
8.3.3 
Reticulations, erythema and ulcerations (REU) score 
The reticulation, erythema and ulcerations score (REU score) was developed by Piboonniyom 
et al. as a semiquantitative scale for the assessment and monitoring of oral lichen planus as well 
as oral graft-versus-host disease (Piboonniyom et al 2005). It measures disease severity based 
on 3 dimensions: reticulation, erythema and ulceration. Whenever possible, the REU 
assessment should be performed by the same evaluator throughout the study. 
The REU score is applied for all patients in the MLP cohort who have an oral presentation of 
the disease. In addition, the REU scoring is also done for patients in the CLP cohort in case they 
have a concomitant oral involvement. 
The assessment is done as follows: 
The oral cavity is divided into the following 10 sites: 
• upper/lower labial mucosa 
• right buccal mucosa 
• left buccal mucosa 
• dorsal tongue 
• ventral tongue 
• floor of mouth 
• hard palate mucosa 
• soft palate/tonsillar pillars 
• maxillary gingiva 
• mandibular gingiva 
The severity of the lesions is scored for each site individually according to the presence of 
reticular/hyperkeratotic, erosive/erythematous and ulcerative lesions: 
• Reticulation: reticular/hyperkeratotic lesions: 0 - 1  
• 0: no white striations 
• 1: presence of white striations or keratotic papules 
• Erythema: erosive/erythematous lesions by area of involvement: 0 - 3  
• 0: no lesion 
• 1: lesions < 1 cm2 
• 2: lesions 1 - 3 cm2 
• 3: lesions > 3 cm2 
• Ulceration: ulcerative lesions by area of involvement: 0-3  
• 0: no lesion 
• 1: lesions < 1 cm2 
• 2: lesions 1 - 3 cm2 


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• 3: lesions > 3 cm2 
For each of the 3 clinical dimensions, a score is then derived by summation of the scores from 
all 10 oral cavity sites: Reticular score = ∑R, erythema score = ∑E, and ulcerative score = ∑U. 
These 3 scores then add up to a total weighted score: ∑R + ∑(E x 1.5) + ∑(U x 2.0). 
8.3.4 
Lichen planopilaris Activity Index (LPPAI) 
The LPPAI is a numeric score to quantify the signs and symptoms of LPP introduced by Chiang 
et al. (Chiang et al 2010). The LPPAI assesses symptoms (pruritus, pain, burning), signs 
(erythema, perifollicular erythema and scale), a measure of activity (pull test) and extension of 
disease. These subjective and objective measures are assigned numeric values to establish a 
disease activity score. Whenever possible, the LPPAI assessment should be performed by the 
same evaluator throughout the study. It is applied for subjects in the LPP cohort only. 
Table 8-3 
LPPAI 
Symptoms  
Score 
Pruritus 
0 - 3 
Pain 
0 - 3 
Burning 
0 - 3 
Signs 
  
Scalp erythema 
0 - 3 
Perifollicular erythema 
0 - 3 
Perifollicular scale 
0 - 3 
Pull test 
0 / 1 & anagen / total 
Spreading 
0 - 2 
Score for signs and symptoms: 0=absent, 1=mild, 2=moderate, 3=severe 
Score for anagen pull test: To conduct the anagen pull test grasp a small group of 10 - 20 hairs 
between the thumb, second and third finger at the scalp end of the hair shafts and pull away 
from the scalp with a slow, firm perpendicular force to slide the fingers to the ends of the hair. 
The result is recorded both as a binary value (0 for no anagen hairs, 1 for the presence of anagen 
hairs) and as anagen hairs/total hairs pulled. 
Score for spreading: 0 = no spreading, 1 = indeterminate, 2 = spreading. When the hair loss is 
difficult to judge, the issue of spreading is recorded as indeterminate. 
The weights given to the symptoms (30%), signs (30%), anagen pull test (25%) and presence 
of spreading (15%) then lead to the final equation: 
LPPAI (0-10) = (pruritus + pain + burning + scalp erythema + perifollicular erythema + 
perifollicular scale)/3 + 2.5x(pull test) + 1.5x(spreading/2) 
8.3.5 
Appropriateness of efficacy assessments 
IGA: Using an IGA type of assessment represents the most widely used assessment strategy to 
evaluate patients' disease severity and improvement. It has been utilized as a primary endpoint 
in several clinical trials investigating psoriasis, and it is routinely used in clinical practice. 


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Available IGA scores are not adequate to assess disease severity in lichen planus, nor to 
describe the complex features of lichen planus. The IGA presented in this study has been 
developed with the contribution of the medical experts included in the Steering Committee, and 
describes the different stages of disease severity harmonizing the scores across the different 
subtypes of lichen planus. This represents the first attempt to develop a unified dermatologic 
score to assess disease severity in patients with lichen planus. 
PSAD: the PSAD is a quantitative score describing the extent of the disease in patients with 
lichen planus. It is not a validated score: in fact, the paucity of RCTs conducted in patients with 
CLP led to the absence of standardized measurements to assess the severity of the disease. The 
only RCT conducted with a biologic therapy in this population (etanercept, NCT00285779) 
utilized this scale: as the disease localization can be different from other skin diseases (i.e. 
psoriasis), BSA may not be the preferred measurement. This study will elucidate the role of 
PSAD in the assessment of disease severity in lichen planus. 
LPPAI: the LPPAI is a numeric score to quantify the signs and symptoms of LPP introduced 
by Chiang et al. (Chiang et al 2010). It is the only available disease-specific score for LPP and 
was used in a number of trials/case series to measure treatment efficacy in this indication 
(Naeini et al 2017; Fonda-Pascual et al 2018; Yang et al 2018) 
REU: the reticulations, erythema and ulcerations score (REU score) was developed by 
Piboonniyom et al. as a semiquantitative scale for the assessment and monitoring of oral lichen 
planus as well as oral graft-versus-host disease (Piboonniyom et al 2005). It measures disease 
severity based on reticulations, erythema and ulceration. It is easy to use, offers a high intra as 
well as inter-observer reliability (Piboonniyom et al 2005; Gobbo et al 2017), correlates with 
pain and reliably reflects improvement attributable to treatment (Park et al 2012). 
8.4 
Safety/Tolerability 
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. 
Safety assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed.  
In the event of a major health care disruption (e.g., pandemic, epidemic) that limits or prevents 
on-site study visits, regular phone will occur (every 4 weeks or more frequently if needed) for 
safety monitoring and discussion of the patient´s health status until the patient can again visit 
the site. Events qualifying for being reported in the CRF (e.g., AE, procedure) should be entered 
as appropriate. If patients cannot visit the site to have urine pregnancy tests done, the urine 
pregnancy test kits can be provided to the patient or shipped directly to the patient’s home (e.g., 
together with the study drug). After appropriate instruction, patients can perform the urine 
pregnancy test at home and report the result to the site. It is important that patients do the 
pregnancy test first and only if the test result is negative proceed with the administration of the 
study drug.  
For details on AE collection and reporting, refer to Section 10.1.1. 


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Table 8-4 
Assessments & Specifications 
Assessment 
Specification 
Physical examination 
A physical examination, including general 
appearance, skin, neck, eyes, ears, nose, throat, 
lungs, heart, abdomen, back, lymph nodes, 
extremities, vascular and neurological systems 
will be performed as indicated in Table 8-1. 
If necessary, based on medical history and/or 
symptoms, additional exams will be performed at 
the discretion of the investigator. 
Whenever possible, assessments for an 
individual subject 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. Clinically relevant findings that are 
present prior to signing informed consent must 
be recorded on the appropriate CRF that 
captures medical history. Significant findings 
made after signing informed consent which meet 
the definition of an Adverse Event must be 
recorded as an adverse event. 
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 subject has been sitting for five 
minutes, with back supported and both feet 
placed on the floor, systolic and diastolic blood 
pressure will be measured twice (measurements 
separated by 1 to 2 minutes) using an 
appropriate device, with a correctly sized cuff 
(Mancia 2007). In case the cuff sizes available 
are not large enough for the subject’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 
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Normal blood pressure will be defined as a 
systolic pressure of 90 to < 120mmHg, and a 
diastolic blood pressure of 60 to < 80 mmHg 
under measurement conditions as outlined 
above. Notable blood pressure will be 
hypertension (systolic ≥ 140 mmHg and/or 
diastolic > 90 mmHg) or hypotension (systolic < 
90 mmHg and/or diastolic < 60 mmHg). A blood 
pressure indicative of pre-hypertension (systolic 
120 to < 140 mmHg and/or diastolic 80 to < 90 
mmHg) will not be regarded as notable 
(Chobanian et al 2003). 
A normal pulse rate will be defined as a rate of 
60 to 100 bpm (beats per minute) under the 
measurement conditions outlined above. 
Notable pulse rates are a rate below 60 bpm 
(bradycardia) or above 100 bpm (tachycardia). 
No specific action is pre-defined within this 
protocol to respond to specific abnormal vital 
signs, as it will be decided by the investigator 
whether and which specific action needs to be 
taken to respond to any abnormal values, taking 
into account the overall status of the subject. 
Height and weight 
Height and body weight will be measured as 
listed in Table 8-1. 
Height and body weight will be measured in 
indoor clothing, but without shoes. Whenever, 
possible, body weight assessments should be 
performed by the same study site staff member; 
the same scale should be used throughout the 
study. 
8.4.1 
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. 
Subjects should avoid smoking within the hour preceding the blood draws. Appendix 1 
(Section 15.1) shows the extended laboratory ranges that are considered clinically notable. No 
specific action is pre-defined within this protocol to respond to specific abnormal laboratory 
values, as it will be decided by the investigator whether and which specific action needs to be 
taken to respond to any abnormal values, taking into account the overall status of the subject. 
The tests will be conducted as defined in the assessment schedule. 
Test Category 
Test Name 
Hematology 
Hematocrit, Hemoglobin, Platelets, Red blood 
cells, White blood cells, Differential (Basophils, 
Eosinophils, Lymphocytes, Monocytes, 
Neutrophils) 


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Chemistry 
Albumin, Alkaline phosphatase, ALT, AST , 
Gamma-Glutamyl-Transferase (GGT), Lactate 
Dehydrogenase (LDH), Bicarbonate, Calcium, 
Magnesium, Phosphorus, Chloride, Sodium, 
Potassium, Creatinine, Total Bilirubin, Total 
Cholesterol, LDL, HDL, Total Protein, 
Triglycerides, Urea, Uric Acid, HbA1c, hs-CRP 
(will not be communicated to the site staff, incl. 
the investigator, or to Novartis during the study 
to maintain blinding)  
Hepatitis Screening 
Hepatitis screening will be conducted at the 
screening visit.  
Pregnancy Test 
Serum / Urine pregnancy test 
8.4.2 
Pregnancy 
The study treatment must not be given to pregnant women; therefore, effective methods of 
birth control must be used for women of childbearing potential (see exclusion criteria 
definitions, Section 5.2). 
A serum Human Chorionic Gonadotropin (β-hCG) test will be performed at Screening in all 
women of childbearing potential. In addition, local urine pregnancy tests must be performed as 
indicated in Table 8-1.  
A positive urine pregnancy test must be followed by a serum β-hCG test aiming at confirming 
the result. Any woman with a confirmed positive pregnancy test during Screening is not eligible 
for randomization. A positive urine pregnancy test requires immediate interruption of study 
treatment until a serum test is performed and found to be negative. If the serum test is positive, 
the subject must be discontinued from the study treatment (see Section 9.1). 
Additional pregnancy testing may be performed as per local requirements. 
8.4.3 
Appropriateness of safety measurements 
The safety assessments selected are standard measures for clinical trials with a biologic, 
immunomodulating agent in dermatologic diseases. 
8.5 
Additional assessments 
The following additional assessments will be applied in this trial: 
• Patient Reported Outcomes (PROs) 
 
 
 
 
• 
  
 
 
 
 
 
 


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8.5.1 
Patient Reported Outcomes (PROs) 
The following PROs will be applied as specified in Table 8-1: 
 
 
 
 
• Patient Assessment of Itch (NRS) 
• Patient Assessment of Pain (NRS) 
• Oral Lichen Planus Symptom Severity Measure (OLPSSM) 
• Dermatology Life Quality Index (DLQI) 
 
 
• SCALPDEX 
All questionnaires will be completed in the language the respondent is most familiar with, at 
the scheduled visit before the subject sees the investigator for clinical assessments. The subject 
should be given sufficient space and time to complete the questionnaires. Oral Lichen Planus 
Symptom Severity Measure (OLPSSM):  
The Oral Lichen Planus Symptom Severity Measure (OLPSSM) was developed by Burke et al. 
as a PRO-based assessment of the symptom experience of subjects with oral lichen planus 
(Burke et al 2019) in clinical studies. 
It includes 7 triggers contributing to soreness of oral lichen planus: Brushing teeth, eating food, 
drinking liquids, smiling, breathing through mouth, talking and touching. These 7 items 
contribute equally to a total OLP symptom severity score, ranging from 0 to 28, with higher 
scores indicating worse severity. 
The OLPSSM is given to all patients in the MLP cohort who have an oral affection of the 
disease. 
Dermatology Life Quality Index: 
The DLQI is a 10-item general dermatology disability index designed to assess health-related 
quality of life (HRQoL) in adult subjects with skin diseases such as eczema, psoriasis, acne, 
and viral warts (Finlay and Khan 1994). The measure is self-administered and includes domains 
of daily activities, leisure, personal relationships, symptoms and feelings, treatment, and 
work/school. The measure is widely used: it has been tested across 32 different skin conditions 
and is available in 55 languages. The recall period is the last week, and the instrument requires 
1 to 2 minutes for completion. Each item has four response categories ranging from 0 (not at 
all) to 3 (very much). “Not relevant” is also a valid response and is scored as 0. The DLQI total 
score is a sum of the 10 questions. Scores range from 0 to 30, with higher scores indicating 
greater HRQoL impairment. Each subscale of the DLQI may also be analyzed separately. 
The DLQI is given to all subjects in the study. 
Scalpdex: 
Scalpdex is a self-administered, health-related quality of life instrument originally developed 
for scalp dermatitis. This 23-item survey evaluates the subject across three major domains – 
symptom, functional, and emotion (Chen 2002). Subjects will be asked to score themselves on 
how true each of the 23 statements has been for them over the past four weeks. The items are 


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scored on a scale of 0-100, where 0=never, 25=rarely, 50=sometimes, 75=often and 100=all the 
time.   
The Scalpdex is given to subjects in the LPP cohort only. 
Patient Assessment of Itch:  
Itch is assessed with the following questions: 
• "Overall, how severe was your lichen planus-related itching during the past 24 hours?" 
• "How severe was your lichen planus-related itching at the worst moment during the past 
24 hours?" 
• "Overall, how bothered were you by your lichen planus-related itching during the past 24 
hours?" 
Answers are given on a numeric rating scale (NRS). The Patient Assessment of Itch is done by 
all subjects. 
Patient Assessment of Pain:  
Pain is assessed with the following questions: 


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• "Overall, how severe was your lichen planus-related pain during the past 24 hours?" 
• "How severe was your lichen planus-related pain at the worst moment during the past 24 
hours?" 
• "Overall, how bothered were you by your lichen planus-related pain during the past 24 
hours?" 
Answers are given on a numeric rating scale (NRS). The Patient Assessment of Pain is done by 
all subjects. 


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8.5.4 
Biomarkers 
Tissue biomarkers: Biopsies 
Punch biopsies will be taken at the visits defined in the assessment schedule (Table 8-1) and 
sent to the  central laboratory or to a local pathologist. Detailed instructions on the biopsy 
procedure, sample harvesting, preparation, storage and shipment are provided in the laboratory 
manual. 
The initial biopsies will be taken at the Screening visit, after the urine pregnancy test has shown 
a negative result for women of childbearing potential. They will be used to obtain a histological 
confirmation of the diagnosis of lichen planus. The histological confirmation of the diagnosis 
is mandatory and an inclusion criterion of this study. It is allowed to leave out the biopsy at 
Screening visit and use a historical biopsy, if available, instead. However, this is only allowed 
in case the historical biopsy has not been taken longer than 3 months prior to Screening visit 
and the stained histology slides are available and can be shared with the central laboratory for 
digitalization. 
 
 
 
 
 


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In case the (screening 
) biopsies have been assessed by a local pathologist, 
stained histology slides should be sent to the central laboratory for digitalization. Appropriate 
slides representative of the current morphological characteristics and activity of the disease 
should be selected. 


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8.5.5 
Other Assessments 
PRO feedback assessment (optional and only applicable for patients/ sites in 
the USA) 
Using qualitative, semi-structured, open ended questions, feedback from a selected number of 
trial patients might be asked in optional exit interviews for their experience with the Patient-
Reported Outcome measures to inform the future lichen planus clinical trial program. 
9 
Study discontinuation and completion 
9.1 
Discontinuation 
9.1.1 
Discontinuation of study treatment 
Discontinuation of study treatment for a subject occurs when the study treatment is stopped 
earlier than the protocol planned duration (i.e., < Week 32) and can be initiated by either the 
subject or the investigator. 
The investigator must discontinue study treatment for a given subject if he/she believes that 
continuation would negatively impact the subject's well-being. Prior to discontinuation this 
should be discussed with and communicated to the sponsor's medical expert.  
Study treatment must be discontinued under the following circumstances: 
• Subject decision 
• Withdrawal of consent 
• Pregnancy 
• A patient on placebo treatment in Treatment Period 1 achieves spontaneous remission 
(defined by an IGA of 0 or 1) at the Week 16 visit 
• Ongoing use of prohibited treatment, use of a prohibited treatment that results in an undue 
safety risk for the subject as per the investigator’s clinical judgment, or receipt of a live 
virus vaccine during the study (as detailed in Section 6.2.2) 
• Any protocol deviation in which study participation might result in a safety risk to the 
subject 
• Emergency unblinding 
• AEs that in the judgment of the investigator/qualified site staff, taking into account the 
patient’s overall status prevent the subject from continuing study treatment 
• Any laboratory abnormalities that in the judgment of the investigator, taking into 
consideration the patient’s overall status, prevents the subject from continuing 
participation in the study 
If discontinuation of study treatment is due to the subject, the investigator should make a 
reasonable effort to understand the primary reason for the subject’s premature discontinuation 
of study treatment and to record this information. 
Subjects who discontinue study treatment should NOT be considered withdrawn from the study 
UNLESS they withdraw their consent (see Section 9.1.3 'Withdrawal of Informed Consent'). 


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Subjects should continue attending planned site visits and perform the study assessments  until 
the last visit of the study period during which they discontinue (Week 16 or Week 32).  
• Subjects, whether they are willing to continue attending further study visits or not, 
should attend an End of Treatment (EOT) visit of the study period during which they 
discontinued (EOT 1 for discontinuation during Treatment Period 1 and EOT 2 for 
discontinuation during Treatment Period 2). The scheduled visit that was planned to take 
place will then not be performed and will be replaced by the EOT visit. 
•  Subjects who are willing to continue will attend visits until Week 16 or Week 32 
according to the schedule and will then move to the Follow-up period. 
• Subjects who are unwilling to continue attending study visits will move directly to the 
Follow up period after their EOT visit 
• Subjects who discontinue study at the same time as study treatment will end their 
participation after their EOT visit (see also Section 9.1.2). 
The investigator must also contact the IRT to register the subject’s discontinuation from study 
treatment. 
If discontinuation occurs because treatment code has been broken, please refer to section 6.6.3.  
If the subject fails to return for EOT assessments for unknown reasons, every effort (e.g. 
telephone, e-mail, letter) should be made to contact the subject/pre-designated contact as 
specified in the Lost to Follow-up section. This contact should preferably be done according to 
the study visit schedule. 
9.1.2 
Discontinuation of study 
If a subject discontinues study during a treatment period, EOT visit should be performed (see 
Section 9.1.1 above). If a subject discontinues study during Follow up period, visit Week 40 
should be performed. 
If the subject cannot or is unwilling to attend any visit(s) after EOT, the site staff should 
maintain regular telephone contact with the subject, or with a person pre-designated by the 
subject. This telephone contact should preferably be done according to the study visit schedule. 
Documentation of attempts to contact the subject should be recorded in the source 
documentation. 
9.1.3 
Withdrawal of informed consent 
Subjects may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a subject: 
• Does not want to participate in the study anymore 
• Does not allow further collection of personal data 
• Does not want any further study related contacts 
• Does not allow analysis of already obtained biologic material 


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In this situation, the investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand the primary reason for the subject’s decision to withdraw his/her consent and 
record this information. 
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 subject are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the subject’s study withdrawal should be made as detailed in the 
assessment table. 
Novartis will continue to keep and use collected study information (including any data resulting 
from the analysis of a subject’s samples until the time of withdrawal) according to applicable 
law. 
For US: all biological samples not yet analyzed at the time of withdrawal may still be used for 
further testing/analysis in accordance with the terms of this protocol and of the informed consent 
form. 
For EU and RoW: all biological samples not yet analyzed at the time of withdrawal will no 
longer be used, unless permitted by applicable law. They will be stored according to applicable 
legal requirements. 
9.1.4 
Lost to follow-up 
For subjects whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator must show "due diligence" by 
documenting in the source documents steps taken to contact the subject, e.g. dates of telephone 
calls, registered letters, etc. A subject should not be considered as lost to follow-up until due 
diligence has been completed or until the end of the study has occurred. 
9.1.5 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit/ risk assessment of participating in the study, practical reasons (including 
slow enrollment), or for regulatory or medical reasons. In taking the decision to terminate, 
Novartis will always consider the subject welfare and safety. Should early termination be 
necessary, subjects must be seen as soon as possible (and be provided instruction on when the 
subject should stop self administrating the drug, when the subject should come for a final visit) 
and treated as a prematurely withdrawn subject. 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 subject’s interests. The investigator or sponsor depending on the local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
9.2 
Study completion and post-study treatment 
Study completion is defined as when the last subject finishes their Study Completion visit 
(Week 40), and any repeat assessments associated with this visit have been documented and 


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followed-up appropriately by the Investigator, or in the event of an early study termination 
decision, the date of that decision. 
A subject will be considered to have completed the study if he/she received a maximum of 30 
weeks of study treatment and upon completion of the scheduled study assessments and 
procedures up to and including visit Week 40. 
The investigator must provide follow-up medical care for all subjects from the study, or must 
refer them for appropriate ongoing care. 
10 
Safety monitoring and reporting 
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 subject or 
clinical investigation subject 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. 
In addition, all reports of intentional misuse and abuse of the product are also considered an 
adverse event irrespective of whether a clinical event has occurred. 
The investigator has the responsibility for managing the safety of individual subject and 
identifying adverse events. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
The occurrence of adverse events must be sought by non-directive questioning of the subject at 
each visit during the study. Adverse events also may be detected when they are volunteered by 
the subject during or between visits or through physical examination findings, laboratory test 
findings, or other assessments. 
Adverse events must be recorded in the Adverse Events eCRF 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 (suspected: Yes/No). 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 


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of underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a 
single subject. 
3. Its duration (start and end dates) or if the event is ongoing, an outcome of not recovered/not 
resolved must be reported. 
4. Whether it constitutes a serious adverse event (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/withdrawn 
6. Concomitant medication or non-drug therapy given 
7. Its outcome: not recovered/not resolved, recovered/resolved, recovered/resolved with 
sequelae, fatal, unknown 
Conditions that were already present at the time of informed consent should be recorded in 
medical history of the subject. 
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 10 weeks 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. 
Worsening of lichen planus in this study is evaluated via the use of efficacy assessments (e.g. 
IGA, REU, LPPAI, PSAD) and is not expected to be captured as an AE in the CRF capturing 
adverse events. Exceptions include cases when a new type of lichen planus is diagnosed, or the 
worsening is so severe that a qualitatively different status is reached. 
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 non-typical in subjects with the 


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underlying disease. Alert ranges for laboratory and other test abnormalities are included in 
Section 15.1. 
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 subject 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 (please refer to the ICH-E2D Guidelines). 
• 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 subject’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 subject 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 subject 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 (please refer to the ICH-
E2D Guidelines). 
All 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.  


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10.1.3 
SAE reporting 
To ensure subject safety, every SAE, regardless of causality, occurring after the subject has 
provided informed consent and until 30 days [after the last study visit (Week 40) must be 
reported to Novartis safety within 24 hours of learning of its occurrence. Detailed instructions 
regarding the submission process and requirements are to be found in the investigator folder 
provided to each site. 
1. Screen Failures (e.g. a subject who is screened but is not treated or randomized): SAEs 
occurring after the subject has provided informed consent until the time the subject is 
deemed a Screen Failure must be reported to Novartis. 
2. Randomized OR Treated Subjects: SAEs collected between time subject signs ICF until 
10 weeks after the subject has discontinued or stopped study treatment  
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 
within 24 hours of the investigator receiving the follow-up information. 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 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 EU Guidance 
2011/C 172/01 or as per national regulatory requirements in participating countries. 
Any SAEs experienced after the 10-week period following the last administration of study 
treatment should only be reported to Novartis Safety if the investigator suspects a causal 
relationship to study treatment. 
10.1.4 
Pregnancy reporting 
Pregnancies 
If a female subject becomes pregnant, the study treatment must be stopped, and the subject 
asked to read and sign the pregnancy ICF to allow the study doctor to ask about the pregnancy. 
To ensure subject 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 Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up should be recorded on the same 


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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. 
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, subject or 
consumer (EMA definition). 
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 
Not applicable 
10.3 
Steering Committee 
A steering committee will be established including disease area experts and investigators 
participating in the trial. 
The steering committee will ensure transparent management of the study according to the 
protocol by recommending and approving modifications as circumstances require. The steering 
committee will review protocol amendments as appropriate. Together with the clinical trial 
team, the steering committee will also develop recommendations for publication of study 
results. The details of the role of the steering committee will be defined in the Steering 
Committee Charter. 


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11 
Data Collection and Database management 
11.1 
Data collection 
Designated investigator staff will enter the data required by the protocol into the Electronic 
CRFs (eCRF). The eCRFs have been built using fully validated secure web-enabled software 
that conforms to 21 CFR Part 11 requirements, Investigator site staff will not be given access 
to the 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 
After final database lock, the investigator will receive copies of the subject 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 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 
World Health Organization (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. 
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO). 
Subjects will fill in their PRO data in a site based tablet. The system will be supplied by a 
vendor, who will also manage the database. The database will be sent electronically to Novartis 
personnel (or designated CRO). 
Randomization codes and data about all study treatment(s) dispensed to the subject and all 
dosage changes will be tracked using an Interactive Response Technology (IRT). The system 
will be supplied by Novartis, who will also manage the database. The data will be sent 
electronically to Novartis at specific timelines. 
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. The 
code break functionality will remain available until study shut down or upon request of 
Novartis. 


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Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked and the treatment codes will be unblinded and made 
available for data analysis. 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 (i.e. eSource DDE or 
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 subject 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 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 subject 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 
subject’s file. The investigator must also keep the original informed consent form signed by the 
subject (a signed copy is given to the subject). 
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 
subjects 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 Randomized Analysis Set (RAS) consists of all randomized subjects. Subjects will be 
analyzed according to the treatment assigned at randomization. 
The Full Analysis Set (FAS) comprises all subjects to whom study treatment has been assigned. 
Subjects will be analyzed according to the treatment assigned to at randomization. Mis-
randomized subjects (mis-randomized in IRT) will be excluded from FAS. Mis-randomized 
subjects are defined as cases where IRT contacts were made by the site either prematurely or 


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inappropriately prior to confirmation of the subject’s final randomization eligibility and no 
study medication was administered to the subject. 
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, where treatment received is defined 
as the randomized/assigned treatment if the subject took at least one dose of that treatment or 
the first treatment received if the randomized/assigned treatment was never received. 
12.2 
Subject demographics and other baseline characteristics 
All data for background and demographic variables will be listed by treatment group and 
subject. Summary statistics will be provided by treatment group. 
Relevant medical history, current medical conditions, results of laboratory screens and any 
other relevant information will be listed by treatment group and subject. 
12.3 
Treatments 
Data for study drug administration and concomitant therapies will be listed by treatment group 
and subject. 
12.4 
Analysis of the primary endpoint(s) 
The primary aim of the study is to demonstrate the efficacy of secukinumab (300 mg Q4W) 
with respect to IGA responder status after 16 weeks of treatment compared to placebo.  The 
detailed definition and the justification of the corresponding primary estimand will be provided 
in the Estimand Charter. 
12.4.1 
Definition of primary endpoint(s) 
The primary endpoint of the study is the proportion of IGA responder at Week 16, where IGA 
response is defined as achievement of absolute IGA score ≤2. 
The analysis of the primary endpoint will be based on the FAS. 
12.4.2 
Statistical model, hypothesis, and method of analysis 
The primary endpoint of IGA response at Week 16 is a binary (yes/no) outcome. Bayesian 
inference based on the non-informative prior of Beta (1/3, 1/3) for each treatment group will be 
used to obtain the posterior distrubution of the treatment difference between secukinumab and 
placebo for the three subtypes, respectively.  
The Bayes PoC criteria to be assessed for the primary endpoint are: 
1) the probability of the treatment difference greater than zero (δ>0) is greater than 90%;  
Pr (δ (secukinumab, placebo),wk16 > 0 | data) > 90%  
And 
2) the probability of the treatment difference exceeding half of the target effect of 0.15 (δ>0.15) 
is greater than 50% 
Pr (δ (secukinumab, placebo),wk16 > 0.15 | data) > 50% 


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where δ denotes the treatment difference between secukinumab and placebo with respect to the 
IGA response at Week 16 
Posterior estimates of the treatment difference and 95% credible interval will be presented. The 
posterior probabilities of achieving the efficacy criteria will be provided. 
12.4.3 
Handling of missing values/censoring/discontinuations 
Subjects who discontinue treatment before Week 16 will be considered to be failures. 
12.4.4 
Sensitivity and Supportive analyses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.5 
Analysis of secondary endpoints 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) 
The secondary endpoints of this study are planned as follow: 
Investigator’s Global Assessment (IGA) score 
IGA responder rate at time points in treatment period 1 other than week 16. The Fisher exact 
test (if suitable) or the chi-square test will be applied to the IGA responder rate at time points 


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other than week 16 and estimates of the difference of the IGA responder rate between the 300 
mg Q4W treatment regimen and placebo groups together with 95% confidence intervals will be 
presented. 
Proportion (%) of IGA responders will be presented by visit from baseline up to the end of 
study for each treatment group. 
Proportion (%) of subjects achieving 2 points improvement in IGA score will be presented by 
visit from baseline up to the end of study for each treatment group. 
Proportion (%) of IGA 0 or 1 will be presented by visit from baseline up to the end of study for 
each treatment group. 
Dermatology Life Quality Index  
Seven scores will be derived from the DLQI: the total score of each of the six dimensions as 
well as the total score over all items. The higher the score, the more quality of life is impaired. 
The DLQI total score will be calculated by summing the score of each question resulting in a 
maximum of 30 and a minimum of 0. 
• DLQI responder: DLQI total score 0 or 1 will be considered as responder. Proportion (%) 
of DLQI responder will be presented by visit up to the end of study for each treatment 
group. 
• Summary statistics will be provided for absolute and percentage change from baseline of 
the total score of each of the six dimensions as well as the total score by visit up to the end 
of study for each treatment group. 
Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease 
The number and percentage of subjects in each category will be presented by visit up to the end 
of study for each treatment group. 
Patient Assessment of Itch (NRS) 
Summary statistics will be provided for absolute and percentage change from baseline of itching 
NRS score by visit for each treatment group up to end of study. 
Patient Assessment of Pain (NRS) 
Summary statistics will be provided for absolute and percentage change from baseline of pain 
NRS score by visit for each treatment group up to end of study. 
Reticular erythematous Ulcerative (REU) score 
Summary statistics will be provided for absolute and percentage change from baseline of REU 
score by visit and for each treatment group up to end of study. 
LPP Activity Index (LPPAI)  
Subjects with an LPPAI reduction greater than 85% over pretreatment values were considered 
responders, with 25% to 85% reduction were considered partial responders, and with less than 
25% reduction were considered non-responders. 
• LPPAI responder and partial responder: LPPAI responder and partial responder will be 
presented by visit up to the end of study for each treatment group. 


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• Summary statistics will be provided for absolute and percentage change from baseline of 
LPPAI score by visit up to the end of study for each treatment group. 
Oral Lichen Planus Symptom Severity Measure (OLPSSM): 
Summary statistics will be provided for absolute and percentage change from baseline of 
OLPSSM score by visit for each treatment group up to end of study. 
Scalpdex: 
Summary statistics will be provided for absolute and percentage change from baseline 
of Scalpdex score by visit for each treatment group up to end of study. 
12.5.2 
Safety endpoints 
All safety evaluations will be performed on the Safety set. 
Adverse events 
Treatment emergent AEs (events started after the first dose of study treatment and within 84 
days after week 32, or events present prior to the first dose of study treatment but increased in 
severity based on preferred term within 84 days after week 32) will be summarized. Only 
primary paths within MedDRA will be considered for AE reporting. 
AEs will be summarized by presenting, for each treatment group, the number and percentage 
of subjects having any AE, having an AE in each primary system organ class and having each 
individual AE (preferred term). Summaries will also be presented for AEs by severity and for 
study treatment related AEs. If a subject reported more than one AE with the same preferred 
term, the AE with the greatest severity will be presented. If a subject reported more than one 
AE within the same primary system organ class, the subject will be counted only once with the 
greatest severity at the system organ class level, where applicable. 
Separate summaries will be provided for death, SAE, other significant AEs leading to 
discontinuation and AEs leading to study treatment discontinuation. 
Vital signs 
Analysis of the vital sign measurements using summary statistics for the change from baseline 
for each post-baseline visit will be performed. These descriptive summaries will be presented 
by vital sign and treatment group. Change from baseline will only be summarized for subjects 
with both baseline and post-baseline values. 
Clinical laboratory evaluations 
The summary of laboratory evaluations will be presented for two groups of laboratory tests 
(hematology and serum chemistry). Descriptive summary statistics for the change from baseline 
to each study visit will be presented. These descriptive summaries will be presented by test 
group, laboratory test and treatment group. Change from baseline will only be summarized for 
subjects with both baseline and post baseline values. 


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12.5.6 
PD relationships 
The 
 other clinically important 
endpoints, such as PSAD, REU, LPPAI will be investigated if appropriate. 
12.5.7 
Patient reported outcomes 
Please refer to Section 12.5 or Section 12.6 for the analysis method of Patient reported 
outcomes. 


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12.7 
Interim analyses 
Primary analysis will be performed after all subjects have completed Week 16 visit. 
Additional analyses may be performed to support health authority interactions as necessary. 
At the end of study, a final analysis of all data collected up to last study visit will be performed 
when all subjects have completed the last study visit. 
12.8 
Sample size calculation 
Total sample size for this study is 108 with 36 subjects in each subtype  
Primary endpoint(s) 
For each subtype, 24 secukinumab 300 mg Q4w treatment regimen subjects and 12 placebo 
subjects assures the 71% probability to claim positive PoC results, based on the assumptions 
that the placebo IGA responder rate is 20% and secukinumab 300 mg Q4w placebo difference 
(delta) of the IGA responder rates is at least 30%. 
For different response rate assumptions on secukinumab 300 mg Q4w and placebo dose 
regimens, the below figure and table show that there is not much difference on the probability 
to claim a successful PoC results between randomization ratios 1:1 and 2:1. Considering the 
absence of previous lichen planus secukinumab data, randomization 2:1 is chosen for this study 
to assure more efficacy and safety data on lichen planus secukinumab subjects. The below 
figure and table also shows the probability to claim a positive PoC results is around 70% when 
the secukinumab 300 mg Q4w placebo difference (delta) of the IGA responder rates is 30% in 
any scenario and greater than 85% when the secukinumab 300 mg Q4w placebo difference 
(delta) of the IGA responder rates is 40% in any scenario. 


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Figure 12-1 
Operating Characteristics on different randomization ratio and 
different response rate assumption 
  
Table 12-1 
Operating Characteristics on different randomization ratio and 
different response rate assumption 
Secukinumab 
response rate 
Placebo response 
rate 
Probability to meet 
target efficacy with 
AIN 18: PBO 18 
Probability to meet 
target efficacy with 
AIN 24: PBO 12  
A(small)=0.4 
0.1 
0.838 
0.793 
B(moderate)=0.5 
0.1 
0.945 
0.923 
C(high)=0.6 
0.1 
0.987 
0.978 
D(very high)=0.7 
0.1 
0.998 
0.996 
E(extreme high)=0.8 
0.1 
1.000 
1.000 
A(small)=0.4 
0.2 
0.543 
0.503 
B(moderate)=0.5 
0.2 
0.767 
0.712 
C(high)=0.6 
0.2 
0.915 
0.871 
D(very high)=0.7 
0.2 
0.980 
0.960 
E(extreme high)=0.8 
0.2 
0.998 
0.993 
A(small)=0.4 
0.3 
0.282 
0.255 
B(moderate)=0.5 
0.3 
0.520 
0.454 
C(high)=0.6 
0.3 
0.751 
0.675 
D(very high)=0.7 
0.3 
0.908 
0.856 
E(extreme high)=0.8 
0.3 
0.980 
0.961 
Operating Characteristics results are from QTD version 3.0.0 


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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 International Conference on Harmonization (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. 
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, subject recruitment procedures (e.g. 
advertisements) and any other written information to be provided to subjects. 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 SOPs, and are performed according to written Novartis processes 


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13.5 
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 subjects 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. 
13.6 
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 subject 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 subject 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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14 
References 
References are available upon request 
Balci DD, Inandi T (2008) Dermatology life quality index scores in Lichen Planus: 
Comparison of psoriasis and healthy controls. Turkderm; 42:127-30. 
Bruin G, Loesche C, Nyirady J, et al (2017) Population Pharmacokinetic Modeling of 
Secukinumab in Patients With Moderate to Severe Psoriasis. J Clin Pharmacol; 57(7):876-85. 
Burke LB, Brennan MT, Ni Riordain R, et al (2019) Novel Oral Lichen Planus Symptom 
Severity Measure for assessing patients' daily symptom experience. Oral Dis; 25(6):1564-72. 
Cassol-Spanemberg J, Blanco-Carrion A, Rodriguez-de Rivera-Campillo ME, et al (2019) 
Cutaneous, genital and oral lichen planus: A descriptive study of 274 patients. Med Oral Patol 
Oral Cir Bucal; 24(1):e1-7. 
Chao TJ (2009) Adalimumab in the management of cutaneous and oral lichen planus. Cutis; 
84:325-28. 
Chen SC (2002) Scalpdex: A quality-of-life instrument for scalp dermatitis. Arch Dermatol; 
138:803-07. 
Cheng H, Oakley A, Conaglen JV, et al (2017) Quality of Life and Sexual Distress in Women 
With Erosive Vulvovaginal Lichen Planus. J Low Genit Tract Dis; 21(2):145–49. 
Chiang C, Sah D, Cho BK, et al (2010) Hydroxychloroquine and lichen planopilaris: efficacy 
and introduction of Lichen Planopilaris Activity Index scoring system. J Am Acad Dermatol; 
62:387-92. 
Chobanian AV, Bakris GL, Black HR, et al (2003) Seventh report of the joint national 
committee on prevention, detection, evaluation, and treatment of high blood pressure. 
Hypertension; 42:1206–52. 
Deen K, McMeniman E (2015) Mycophenolate mofetil in erosive genital lichen planus: A 
case and review of the literature. J Dermatol; 42: 311-14. 
Doherty SD, Van Voorhees A, Lebwohl MG, et al (2008) National Psoriasis Foundation 
consensus statement on screening for latent tuberculosis infection in patients with psoriasis 
treated with systemic and biologic agents. J Am Acad Dermatol; 59:209-17. 
Finlay AY, Khan GK. 1994. Dermatology Life Quality Index (DLQI)- a simple practical 
measure for routine clinical use. Clin. Exp. Dermatol; 19(3):210-16. 
Fonda-Pascual P, Fernández-González P, Moreno-Arrones OM, et al (2018) Pustular 
Secondary Cutaneous Aspergillosis in an Immunosuppressed Patient. Actas Dermosifiliogr; 
109:287-90. 
Gobbo M, Rupel K, Zoi V, et al (2017) Scoring systems for Oral Lichen Planus used by 
differently experienced raters. Med Oral Patol Oral Cir Bucal; 22(5):e562-71. 
Gorouhi F, Davari P, Fazel N (2014) Cutaneous and mucosal lichen planus: A comprehensive 
review of clinical subtypes, risk factors, diagnosis, and prognosis. Scientific World Journal; 
2014(742826):1-22. 


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Gueiros LA, Arao T, Souza T, et al (2018) IL17A polymorphism and elevated IL17A serum 
levels are associated with oral lichen planus. Oral Dis; 24:377–83. 
Hazra SC, Choudhury AM, Khondker L, et al (2013) Comparative efficacy of methotrexate 
and mini pulse betamethasone in the treatment of lichen planus. Mymensingh Med J; 
22(4):787-97. 
Husein-ElAhmed H, Gieler U, Steinhoff M (2019) Lichen planus: a comprehensive evidence-
based analysis of medical treatment. J Eur Acad Dermatol Venereol; 33:1847–62. 
 
Langley RG, Elewski BE, Lebwohl M, et al (2014) Secukinumab in plaque psoriasis- Results 
of two phase 3 trials. N. Engl. J. Med; 371(4):326-38. 
Le Cleach L, Chosidow O (2012) Clinical practice. Lichen planus. N. Engl. J. Med; 
366(8):723-32. 
Lunge S, Patil S, Manjunathswamy BS (2016) A comparative study of methotrexate & low 
molecular weight heparin for the treatment of generalized lichen planus. Ind J Clin and Exp 
Dermatol; 2(4):153-58. 
Mancia G (2007) Blood pressure reduction and cardiovascular outcomes: Past, present, and 
future. Am. J. Cardiol; 100suppl:3J–9J. 
Manuel O, Kumar D (2008) QuantiFERON-TB® Gold assay for the diagnosis of latent 
tuberculosis infection. Expert Rev. Mol. Diagn; 8(3):247-55. 
Naeini FF, Saber M, Asilian A, et al (2017) Clinical Efficacy and Safety of Methotrexate 
versus Hydroxychloroquine in Preventing Lichen Planopilaris Progress: A Randomized 
Clinical Trial. Int J Prev Med; 8:37-44. 
Neuenschwander B, Wandel S, Roychoudhury S, et al (2015) Robust exchangeability designs 
for early phase clinical trials with multiple strata. Pharmaceut Statist; 15:123-34. 
Park HK, Hurwitz S, Woo SB (2012) Oral lichen planus: REU scoring system correlates with 
pain. Oral Surg Oral Med Oral Pathol Oral Radiol; 114(1):75-82. 
Patrick DL, Burke LB, Powers JH, et al (2007) Patient-reported outcomes to support medical 
product labeling claims: FDA perspective. International Society for Pharmacoeconomics and 
Outcomes Research; 10(2):S125–S137. 
Piboonniyom SO, Treister N, Pitiphat W, et al (2005) Scoring system for monitoring oral 
lichenoid lesions: a preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod; 
99(6):696-703. 
Radwan-Oczko M, Zwyrtek E, Owczarek JE, et al (2018) Psychopathological profile and 
quality of life of patients with oral lichen planus. J Appl Oral Sci; 26:1-9. 
Schmidt T, Solimani F, Pollmann R, et al (2018) TH1/TH17 cell recognition of desmoglein 3 
and bullous pemphigoid antigen 180 in patients with lichen planus. J. Allergy Clin. Immunol; 
142(2):669-72. 


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Shaker O, Hassan AS (2012) Possible role of interleukin-17 in the pathogenesis of lichen 
planus. Br. J. Dermatol; 166:1367-68. 
Solimani F, Pollmann R, Schmidt T, et al (2019) Therapeutic Targeting of Th17/Tc17 Cells 
Leads to Clinical Improvement of Lichen Planus. Front Immunol; 10:1-10. 
Thandar Y, Maharajh R, Haffejee F, et al (2019) Treatment of cutaneous lichen planus (Part 
1): A review of topical therapies and phototherapy. Cogent Medicine; 6:1-21. 
Thongprasom K, Dhanuthai K (2008) Steriods in the treatment of lichen planus: a review. J 
Oral Sci; 50(4):377-85. 
Tziotzios C, Brier T, Lee JYW, et al (2018) Lichen planus and lichenoid dermatoses: 
Conventional and emerging therapeutic strategies. J. Am. Acad. Dermatol; 79:807-18. 
Welz-Kubiak K, Reich A, Szepietowski JC (2017) Clinical Aspects of Itch in Lichen Planus. 
Acta Derm. Venereol; 97:505–08. 
Yang CC, Khanna T, Sallee B, et al (2018) Tofacitinib for the treatment of lichen planopilaris: 
A case series. Dermatol Ther; 31:1-4. 
Zakrzewska JM, Chan ES, Thornhill MH (2005) A systematic review of placebo-controlled 
randomized clinical trials of treatments used in oral lichen planus. Br. J. Dermatol; 
153(2):336-41. 
Zhang J, Zhou G, Du GF, et al (2011) Biologics, an alternative therapeutic approach for oral 
lichen planus. J. Oral Pathol. Med; 40:521–24. 


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15 
Appendices 
15.1 
Appendix 1: Clinically notable laboratory values and vital signs 
Clinically notable laboratory values  
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. 
No specific action is pre-defined within this protocol to respond to specific abnormal laboratory 
values, as it will be decided by the investigator whether and which specific action needs to be 
taken to respond to any abnormal values, taking into account the overall status of the subject. 
Liver Function and Related Variables 
Alanine transaminase (ALT) (SGPT): > 3 x Upper Limit of Normal (ULN) 
Aspartate transaminase (AST) (SGOT): > 3 x ULN 
Total bilirubin: > 2 x ULN 
Alkaline phosphatase: > 2.5 x ULN 
Renal Function 
Creatinine (serum): > 1.5 x ULN 
Hematology 
Hemoglobin: ≥ 2 g/dl decrease from baseline 
Platelet count: < Lower Limit of Normal (LLN) 
White blood cell count: < 0.8 x LLN 
Neutrophils: < 0.9 x LLN 
Eosinophils: > 1.1 x ULN 
Lymphocytes: > 1.1 x ULN 
Clinically notable vital signs  
Notable values for Vital signs are defined in Table 8-4. 
No specific action is pre-defined within this protocol to respond to specific abnormal vital signs, 
as it will be decided by the investigator whether and which specific action needs to be taken to 
respond to any abnormal values, taking into account the overall status of the subject. 
 
 


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15.3 
Appendix 2: Determination of Tuberculosis status 
Determination of tuberculosis (TB) status will be required before administration of study 
treatment and should be performed as defined by local guidelines. TB status must be determined 
by medical history, signs, symptoms and TB central lab testing. Any significant findings will 
be recorded in the relevant TB assessment eCRF and the Medical History eCRF, as necessary. 
A central lab testing will be performed to assess the TB status at screening for all subjects. This 
test will only be used to determine subject’s eligibility for the trial. The test will be used to 
screen the subject population for latent tuberculosis infection (Doherty et al 2008). 
This blood-based assay is specific for Mycobacterium tuberculosis and is not influenced by 
previous Bacillus Calmette-Guérin vaccination or by exposure to other Mycobacteria species. 
Furthermore, this test, in contrast to the purified protein derivative (PPD) skin test, is also 
insensitive to a booster effect since the subject is not exposed to the vaccine. The assay measures 
the production of interferon-gamma and presents it relative to a negative and a positive control 
sample (Manuel and Kumar 2008). The tuberculosis assay test will be supplied by the central 
laboratory. Details on the collection, shipment of samples and reporting of results by the central 
laboratory are provided to investigators in the study-specific laboratory manual. 
Positive or indeterminate tests must be recorded on the Tuberculosis assessment eCRF; the 
workflow of sample handling in case of positive or indeterminate test results is provided 
in Figure 15-1. 
a. If the test result is negative, the subject may be randomized. 
b. If the test result is positive, the investigator should perform a work-up for the test result as 
per local procedures. If a TB work-up was conducted prior to the screening of the subject, results 
of the work-up can be used to assess eligibility if the work-up was conducted within 12 weeks 
prior to randomization. 
Subjects positive for latent TB per work-up may be randomized to the trial if sufficient 
treatment has been initiated according to local routine clinical practice and will be maintained 
for the prescribed duration. Subjects positive for active TB per work-up are not eligible for the 
study. Subjects negative for TB (no signs of latent or active TB) per work-up may be 
randomized to the trial. 
c. If the test result is indeterminate, the investigator may repeat the test once or may proceed 
directly to perform the work-up for the test result as per local procedures. This action is at 
the discretion of the investigator. If a TB work-up was conducted prior to the screening of the 
subject, results of the work-up can be used to assess eligibility if the work-up was conducted 
within 12 weeks prior to randomization. 
i. If the second test is, the subject may be randomized. 
ii. If the second test is positive or indeterminate, the investigator should perform workup as per 
local guidelines. Subject positive for latent TB per workup may be randomized to the trial if 
sufficient treatment has been initiated according to local routine clinical practice and will be 
maintained for the prescribed duration. The subject will not be eligible for randomization if 
“active tuberculosis is present ”or“ latent tuberculosis is present” and is untreated per local 
guidelines. 


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iii. Subjects negative for TB per workup (no signs of latent or active TB) may be randomized 
to the trial if the workup was conducted 12 within weeks prior to randomization. . 
If eligibility is being assessed with only 1 test result and a TB work-up (i.e., no second TB test 
will be performed), the TB test to assess eligibility must have been done via the central 
laboratory for the study within the Screening Period (within 4 weeks prior to randomization) 
and TB work-up will only be considered if it was completed within 12 weeks prior to 
randomization. 


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Figure 15-1 
Tuberculosis screening flowchart 
 

SAP_001.pdf: 
Clinical Development 
AIN457/ Secukinumab/Cosentyx®
CAIN457S12201 / NCT04300296
A proof of concept study to evaluate the efficacy, safety and tolerability of 
secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven 
forms of lichen planus not adequately controlled with topical therapies - 
PRELUDE 
Statistical Analysis Plan (SAP) 
Author: 
Statistician, 
 
Document type: 
SAP Documentation 
Document status: 
Amendment 3 
Release date: 
19-May-2022
Number of pages: 
72 
Property of Novartis 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 


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Document History – Changes compared to previous final version of SAP 
Date 
Reason 
for update 
Outcome 
for 
update 
Section and title impacted (Current) 
 
2020/7/17 
Creation of 
final 
version 
N/A - First version NA 
2021/11/23 To address 
comments 
during dry 
run 
preparation 
 
• Amendment 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Section 2.4.1: clarified the definition of 
duration of exposure. 
 
 
 
• Section 2.6 
: specified the use of 
data after treatment discontinuation for 
secondary 
 endpoints. 
• Section 2.7.1: added analyses of exposure-
adjusted incidence rate of AEs and risks. 
 
 
 
• Section 5.4: clarified the description of the 
estimand framework. 
• Section 5.5.2: added the section “Multiple 
imputations 
for 
supplementary 
analysis: 
Hypothetical scenario”. 
• Section 5.6: Rule of exclusion criteria of 
analysis sets. Added a PD “M-INCL05-
randomized in error” which causes subjects to 
be excluded from the Randomized set. 
2021/12/14 
To 
clarify 
endpoints 
and 
analyses  
following 
dry 
run 
completion 
 
• Amendment 2 
• Section 
1.1 
and 
2.14: 
removed 
the 
descriptions no longer applicable after dry 
run. 
• Section 2.3.2: updated the disease history 
variables that would be summarized in the 
baseline characteristics table. 
• Section 2.6.1: added the analyses of 
Scalpdex by dimension. 


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AIN457S12201 
 
2022/5/19 
To 
add 
analysis for 
the 
final 
CSR 
• Amendment 3 
• Table 2-1: updated the treatment group 
labels. 
• Section 2.6.3: updated the BOCF imputation 
from treatment period 1 to the entire treatment 
period.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table of contents 
Table of contents ................................................................................................................. 4 
List of tables ........................................................................................................................ 7 
List of figures ...................................................................................................................... 8 
List of abbreviations ............................................................................................................ 9 
1 
Introduction ....................................................................................................................... 11 
1.1 
Study design........................................................................................................... 11 
1.2 
Study objectives and endpoints ............................................................................. 14 
2 
Statistical methods ............................................................................................................. 18 
2.1 
Data analysis general information ......................................................................... 18 
2.1.1 
General definitions ................................................................................ 18 
2.2 
Analysis sets .......................................................................................................... 19 
2.2.1 
Subgroup of interest .............................................................................. 20 
2.3 
Patient disposition, demographics and other baseline characteristics ................... 21 
2.3.1 
Patient disposition ................................................................................. 21 
2.3.2 
Demographics and other baseline characteristics ................................. 21 
2.4 
Treatments (study treatment and concomitant medications) ................................. 23 
2.4.1 
Study treatment / compliance ................................................................ 23 
2.4.2 
Visit windows........................................................................................ 23 
2.4.3 
Multiple assessments within visit windows .......................................... 24 
2.4.4 
Prior, concomitant and post therapies ................................................... 25 
2.5 
Analysis of the primary objective .......................................................................... 26 
2.5.1 
Primary endpoint ................................................................................... 26 
2.5.2 
Statistical hypothesis, model, and method of analysis .......................... 26 
2.5.3 
Handling of missing values/censoring/discontinuations. ...................... 27 
2.5.4 
Supplementary analyses ........................................................................ 27 
2.6 
Analysis of secondary objectives ........................................................................... 28 
2.6.1 
Secondary endpoints ............................................................................. 28 


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2.6.2 
Statistical hypothesis, model, and method of analysis .......................... 31 
2.6.3 
Handling of missing values/censoring/discontinuations ....................... 31 
2.7 
Analyses of safety endpoints ................................................................................. 31 
2.7.1 
Adverse events (AEs) ............................................................................ 32 
2.7.2 
Deaths .................................................................................................... 33 
2.7.3 
Laboratory data ..................................................................................... 33 
2.7.4 
Other safety data ................................................................................... 33 
 
 34 
2.9 
PD 
PD analyses......................................................................................... 34 
 
 34 
2.11 
Patient-reported outcomes ..................................................................................... 34 
 
 35 
 
 35 
 
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2.14 
Interim analysis ...................................................................................................... 39 
3 
Sample size calculation ..................................................................................................... 40 
 
 41 
5 
Appendix ........................................................................................................................... 42 
5.1 
Imputation rules ..................................................................................................... 42 
5.1.1 
Study drug ............................................................................................. 42 
5.1.2 
AE date imputation ............................................................................... 42 
5.1.3 
Concomitant medication date imputation ............................................. 43 
5.1.4 
Medical history date imputation............................................................ 44 
5.1.5 
Other imputations .................................................................................. 44 
5.2 
AEs coding/grading ............................................................................................... 44 
5.3 
Laboratory parameters derivations ........................................................................ 44 
5.4 
Estimand Charter ................................................................................................... 45 
5.4.1 
Introduction ........................................................................................... 45 
5.4.2 
Primary estimand .................................................................................. 46 
5.5 
Statistical models ................................................................................................... 48 
5.5.1 
General specifications ........................................................................... 48 
5.5.2 
Multiple imputations for supplementary analysis: Hypothetical 
scenario ................................................................................................. 48 
 
 49 
5.6 
Rule of exclusion criteria of analysis sets.............................................................. 67 
5.7 
Descriptions of some efficacy endpoints ............................................................... 67 
5.7.1 
Investigator's Global Assessment grading (IGA) .................................. 67 
5.7.2 
Patient Assessment of Itch (NRS) ......................................................... 69 
5.7.3 
Patient Assessment of Pain (NRS) ........................................................ 69 
5.7.4 
Physician´s assessment of surface area of disease (PSAD) .................. 69 
5.7.5 
Reticulations, erythema and ulcerations (REU) score .......................... 70 
5.7.6 
Lichen planopilaris Activity Index (LPPAI) ......................................... 71 


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6 
Reference ........................................................................................................................... 72 
 
List of tables 
Table 1-1 
Objectives and related endpoints. ........................................................ 14 
Table 2-1 
Summary statistics specifications ......................................................... 20 
Table 2-2 
Demographics and other baseline characteristics ................................. 21 
Table 2-3 
Assessment windows for scheduled visits ............................................ 24 
Table 2-4 
Rules for selecting values for analysis within a given visit window .... 25 
Table 2-5 
Overview of analysis methods for secondary efficacy variables .......... 31 
Table 2-6 
Overview of analyses on some safety endpoints ................................... 32 
Table 2-7 
Criteria for notable vital sign abnormalities .......................................... 34 
 
 38 
Table 3-1 
Operating Characteristics on different randomization ratio and 
different response rate assumption ........................................................ 41 
 
 51 
 
 
 52 
 
 
 53 
 
 
 54 
 
 
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 61 
 
... 61 
 
 63 
 
 64 
 
 65 
 
 66 
Table 5-18 
Subject Classification ............................................................................ 67 
Table 5-19 
IGA ........................................................................................................ 67 
Table 5-20 
LPPAI .................................................................................................... 71 
 
List of figures 
Figure 1-1 
Study design .......................................................................................... 13 
Figure 3-1 
Operating Characteristics on different randomization ratio and 
different response rate assumption ........................................................ 40 
 
 50 


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List of abbreviations 
AE 
Adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Classification 
CLP 
Cutaneous lichen planus 
CSR 
Clinical Study report 
DLQI 
Dermatology Life Quality Index  
FAS 
Full Analysis Set 
eCRF 
Electronic Case Report Form 
EOT 
End of treatment 
 
 
IGA 
Investigator’s Global Assessment  
LP 
Lichen planus 
LPP 
Lichen planopilaris 
LPPAI 
Lichen Planopilaris Activity Index  
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
MLP 
Mucosal lichen planus 
NRS 
Numeric Rating Scale 
OLPSSM 
Oral Lichen Planus Symptom Severity Measure  
PBO 
Placebo 
 
  
 
 
PT 
Preferred Term 
 
 
PD 
Pharmacodynamics 
PRO 
Patient-reported Outcomes 
PSAD 
Physician Assessment of Surface Area of Disease 
Q2W 
Once every 2 weeks 


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Q4W 
Once every 4 weeks 
RAP 
Report and Analysis Process 
RAS 
Randomized Analysis Set 
REU 
Reticular Erythematous Ulcerative 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
 


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1 
Introduction 
Data will be analyzed by Novartis according to the data analysis [Section 12] of the study 
protocol that is available in [Appendix 16.1.1 of the CSR]. Important information is given in 
the following sections and details are provided, as applicable, in [Appendix 16.1.9 of the CSR]. 
This document covers statistical and analytical plans for the primary endpoint analysis i.e after 
all subjects have completed their Week 16 visit as well for the final analysis i.e after all subjects 
have completed the follow up period following the 32 week treatment period.  
1.1 
Study design  
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial 
assessing the efficacy and safety of secukinumab 300 mg in two different dosing regimens in 
patients with biopsy-proven forms of lichen planus. 
The study consists of three cohorts (one cohort per lichen planus subtype: cutaneous lichen 
planus (CLP), mucosal lichen planus (MLP) and lichen planopilaris (LPP)) and 4 study periods. 
Patients are assigned to one of the three cohorts based on their predominant subtype and 
undergo a biopsy to confirm the clinical diagnosis at the screening visit: 
• Predominantly cutaneous lichen planus 
• Predominantly mucosal lichen planus 
• Lichen planopilaris 
Each cohort will follow the same study design across the 4 periods: 
• Screening Period: up to 4 weeks prior to baseline 
• Treatment Period 1: baseline to Week 16 
• Treatment Period 2: Week 16 to Week 32 
• Follow-up: 8 weeks after Week 32 
Screening period: 
A screening period of up to 4 weeks is used to assess patient´s eligibility for the trial and to 
washout/ adjust prohibited medications. The screening period covers the time from the signature 
of informed consent/screening visit (-4 weeks) to the randomization visit (Week 0).  
Treatment Period 1: 
Treatment Period 1 is placebo-controlled and covers the time from Week 0 (randomization visit) 
to Week 16. Patients who meet all eligibility criteria are randomized in a 2:1 ratio to one of the 
following two treatment arms within their cohort: 
• Secukinumab 300 mg every 4 weeks (Q4W) arm: subjects receive a weekly induction 
treatment from baseline to Week 4 followed by secukinumab 300 mg every 4 weeks. 


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• Placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (Q2W) arm: 
subjects receive matching placebo injections. 
Thirty-six patients will be randomized per cohort, 24 to active and 12 to placebo treatment, 
which means that the study will enroll approximately 108 subjects in total. 
In Treatment Period 1 all subjects receive weekly subcutaneous injections of blinded study drug 
(either 300 mg secukinumab or placebo) at Weeks 0, 1, 2, 3 and 4. Thereafter the frequency of 
blinded study drug injections for all subjects is every 4 weeks up to Week 16. Home 
administration of study drug is not allowed during Treatment Period 1, except for the case of a 
pandemic. Subjects who complete Treatment Period 1 roll over to Treatment Period 2 at the 
Week 16 visit. The only exception are subjects from the placebo for 16 weeks followed by 
secukinumab 300 mg every 2 weeks arm, who achieve spontaneous remission at the Week 16 
visit. Spontaneous remission is defined as an IGA of 0 or 1 at Week 16. These subjects do not 
proceed to Treatment Period 2 to avoid unnecessary treatment. Instead, they will directly enter 
the Follow-up Period after the Week 16 visit.  
Treatment Period 2: 
Treatment Period 2 starts at the Week 16 visit and covers the time until the Week 32 visit. 
Depending on the treatment arm, subjects receive the following treatments: 
• Secukinumab 300 mg Q4W arm: subjects receive continued treatment with secukinumab 
300 mg every 4 weeks plus matching placebo injections to maintain treatment blinding. 
• Placebo for 16 weeks followed by secukinumab 300 mg Q2W arm: subjects are switched 
to active treatment with secukinumab 300 mg every 2 weeks including a weekly induction 
starting from Week 16 to Week 20, with the exception of subjects achieving remission by 
Week 16. 
The Week 16 injection is the first injection of Treatment Period 2. 
Treatment remains blinded during Treatment Period 2. This means that starting at the Week 16 
visit all subjects receive an induction consisting of weekly blinded study drug injections (either 
secukinumab 300 mg or placebo) at Weeks 16, 17, 18, 19 and 20, followed by blinded study 
drug injections every 2 weeks. 
The last study drug injection is administered at Week 30. The end of Treatment Period 2 is 
Week 32. After Week 32, all subjects enter the Follow-up Period.  
Subjects who discontinue study treatment prematurely for any reason other than withdrawal of 
informed consent should not be considered as discontinued from the study. Subjects should 
continue attending planned site visits and perform study assessments until the last visit of the 
treatment period during which they discontinue (Week 16 or Week 32).  
Subjects, whether they are willing to continue attending further study visits or not, should attend 
the End of Treatment visit (EOT) during which they discontinued (EOT 1 for discontinuation 


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during Treatment Period 1 and EOT 2 for discontinuation during Treatment Period 2). EOT 1 
should be performed 4 weeks after the last dose of study drug, and EOT 2 should be performed 
2 weeks after last dose of study drug. 
Follow-up: 
There is an 8-week Follow-up Period after Week 32. The End of Study (EOS) is reached at 
Week 40. If a subject discontinues study during Follow-up period, visit Week 40 has to be 
performed. 
Figure 1-1 
Study design 
 
The primary endpoint will be evaluated at Week 16, where Week 16 represents a widely used 
and well-accepted timing for the assessment of key endpoints in several inflammatory skin 
diseases such as psoriasis, hidradenitis suppurativa or atopic dermatitis, as well as an established 
timepoint to detect the efficacy of secukinumab. The total study duration, up to 32 weeks of 
treatment, allows the collection of long-term efficacy and safety data beyond 16 weeks of 
treatment. Subjects who have been on placebo treatment in Treatment Period 1 are switched to 
active treatment with secukinumab 300 mg every 2 weeks (starting with the regular weekly 
induction). This enables placebo treated patients to receive active treatment during the trial as 
well. Furthermore, it allows the assessment of efficacy and safety of the 2-weekly dosing 
regimen in lichen planus. 
The purpose of this primary endpoint analysis is to assess whether secukinumab shows efficacy 
and safety in the selected lichen planus subtypes at an early time point (proof of concept). This 


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enables planning of further clinical development of secukinumab in lichen planus. At the end 
of the study, a final analysis will be performed once all patients have completed their last study 
visit. All patients, investigators and site personnel will remain blinded until the final database 
lock. 
Further analyses are currently not planned. However, an unscheduled analysis could be 
conducted if a compelling reason arises, for example, if requested by health authorities. 
1.2 
Study objectives and endpoints 
The purpose of this proof of concept study is to elucidate the efficacy of secukinumab in the 
treatment of adult patients with biopsy-proven lichen planus not adequately controlled by 
topical therapies and to assess the safety and tolerability over 32 weeks. 
Table 1-1 
Objectives and related endpoints. 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
• 
To demonstrate the clinical efficacy of 
secukinumab 300 mg every 4 weeks (Q4W) in 
subjects with cutaneous lichen planus (CLP), 
mucosal lichen planus (MLP), or lichen 
planopilaris (LPP) inadequately controlled by 
topical therapies, with respect to improvement in 
Investigator’s Global Assessment (IGA) 
response by Week 16, compared to placebo. 
• 
Achievement of IGA response at Week 
16 
Patients diagnosed with biopsy-proven 
forms of CLP, MLP or LPP will be 
considered responders if they achieve an 
absolute IGA score ≤2 at Week 16 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
• 
The secondary objectives of this trial comprise 
the following: 
- evaluate the efficacy of secukinumab 300 mg 
Q4W 
compared 
to 
placebo throughout 16 
weeks in Treatment Period 1; 
- 
evaluate 
the 
long 
term 
efficacy 
of 
secukinumab 300 mg Q4W throughout 32 weeks 
in Treatment Period 2; 
- evaluate the efficacy of secukinumab 300 mg 
Q2W in Treatment Period 2; 
- evaluate the safety profile of secukinumab 300 
mg throughout the duration of the study. 
Detailed assessments are described the next 
section. 
 
All subtypes 
Investigator's Global Assessment (IGA) 
• 
Achievement of at least 2 points 
improvement 
from 
baseline 
in 
the IGA score  at Week 16 and 32, and 
throughout the duration of the study 
• 
Achievement of IGA 0/1 score at Week 
16 and 32, and throughout the duration 
of the study  


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Objective(s) 
Endpoint(s) 
• 
Dermatology Life Quality Index (DLQI)  
• 
Absolute and relative change in DLQI 
from baseline to Week 16 and 32, and 
throughout the duration of the study 
• 
Achievement of DLQI 0/1 score at Week 
16 and 32, and throughout the duration 
of the study, among the subset of 
subjects with DLQI ≥2 at baseline 
• 
Patient assessment of itch (NRS) 
• 
Absolute and relative change in NRS 
from baseline to Week 16 and 32, and 
throughout the duration of the study 
• 
Patient assessment of pain (NRS) 
• 
Absolute and relative change in NRS 
from baseline to Week 16 and 32, and 
throughout the duration of the study 
• 
To assess the safety and tolerability of 
secukinumab in subjects with lichen planus. 
• 
Adverse events, laboratory values, vital 
signs 
Cutaneous Lichen Planus (CLP) 
 
• 
Physician Assessment of Surface Area of 
Disease (PSAD) for Skin Disease 
• 
Absolute and relative frequencies in 
PSAD from baseline to Week 16 and 32, 
and throughout the duration of the study 
Mucosal Lichen Planus (MLP) 
 
• 
Reticular Erythematous Ulcerative (REU) score 
• 
Absolute and relative change in REU 
score from baseline to Week 16 and 32, 
and throughout the duration of the study 
• 
Oral Lichen Planus Symptoms Severity Measure 
(OLPSSM) score 
• 
Absolute and relative change in 
OLPSSM score from baseline to week 
16 and 32, and throughout the duration 
of the study 
Lichen Planopilaris (LPP) 
 
• 
LPP Activity Index (LPPAI) 
• 
Absolute and relative change in LPPAI 
score from baseline to Week 16 and 32, 
and throughout the duration of the study 
• 
SCALPDEX Questionnaire 
• 
Absolute and relative change in 
SCALPDEX Questionnaire score from 
baseline to Week 16 and 32, and 
throughout the duration of the study 


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2 
Statistical methods 
2.1 
Data analysis general information 
Novartis will be performing the analysis. Statistical software SAS version 9.4 or later will be 
used. 
All data will be analyzed separately for each cohort (predominantly CLP, predominantly MLP, 
LPP), unless specified otherwise.  
Summary statistics for continuous variables will include N, mean, standard deviation, minimum, 
lower quartile, median, upper quartile, maximum. Summary statistics for discrete variables will 
be presented in contingency tables and will include absolute and relative frequencies. 
All listings will be presented by cohort and treatment groups. 
Footnotes in the outputs will be kept to a minimum. 
Footnotes will generally be provided for 
• abbreviations used in the output; abbreviations used on several outputs, e.g. for listings in 
[Appendix 16.2] can be presented on a separate page and do not have to be repeated as 
footnotes on each listing 
• sorting order of categories, e.g. for sorting within MedDRA (Medical Dictionary for 
Regulatory Activities) hierarchy levels 
• MedDRA version used for reporting of MedDRA coded data 
Footnotes will generally NOT be given for 
• units displayed on the output 
• interpretation of results (e.g. “odds ratio larger 1 favors active treatment”) 
• information that can be retrieved from the statistical section of the clinical study report (CSR) 
unless it is not identifiable from the output, e.g. 
• explanation of analysis model used unless results of more than one model are displayed 
in an output 
• derivations of variables (e.g. BMI will not be explained in a footnote) 
• information that will be provided in the clinical study protocol and/or methods section of 
the CSR (e.g. baseline definition if this is specified in the statistical section of the CSR) 
2.1.1 
General definitions  
2.1.1.1 
Study Day 1 and other study days 
The first day of administration of randomized study treatment (first dose) is defined as Study 


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Day 1 or Day 1.  
All other study days will be labeled relative to Day 1. For event dates on or after Day 1, study 
day for an event date is calculated as Date of event – [Day 1] + 1, i.e., Day 2, Day 3, etc., will 
be one day, two days, etc., after Day 1, respectively. For event dates before Day 1, study day 
for an event date is calculated as Date of event – [Day 1], i.e., Day -1, Day -2, etc., will be one 
day, two days, etc., before Day 1, respectively. Duration of an event will be calculated as (Event 
end date – Event start date + 1). 
The descriptor “Day 0” will not be used. 
2.1.1.2 
Screening, baseline and post-baseline definitions 
Screening refers to any procedures (e.g., checking inclusion and exclusion criteria) performed 
prior to the first dose of study treatment. Per protocol, subject informed consent must be 
obtained prior to performing any study related activity. The date of signing informed consent is 
the start date of screening period. Any assessment obtained during the screening period will be 
labeled screening assessment. Assessments made on Day 1 may occur before or after the first 
dose.  
For efficacy analyses, baseline is the last assessment (including unscheduled visits) obtained on 
or before the randomization day. All assessments obtained after randomization are considered 
as post-baseline unless otherwise specified. 
For safety analyses, baseline is the last assessment (including unscheduled visits) obtained (on 
or) before the first dose (day) of study treatment. All assessments obtained after the first dose 
(day) of study treatment are considered as post-baseline unless otherwise specified. 
Of note, baseline will be derived based on randomization day or first dose day, exact 
randomization or dosing time is not considered. 
2.1.1.3 
Day of last dose of study treatment 
The date of last dose will be collected via the CRF. The subject’s exposure will be calculated 
considering the end of study period visit (including follow-up visits F4, F8) or last dose day 
+84 days whichever occurs earlier.  
2.2 
Analysis sets 
The following analysis sets will be used for the data analysis. Rules of exclusion criteria of 
analysis are detailed in Section 5.6.  
The Randomized Analysis Set (RAS) consists of all randomized subjects. Subjects will be 
analyzed according to the treatment assigned at randomization. 
The Full Analysis Set (FAS) comprises all subjects to whom study treatment has been assigned. 
Subjects will be analyzed according to the treatment assigned to at randomization. Mis-
randomized subjects (mis-randomized in IRT) will be excluded from FAS. Mis-randomized 
subjects are defined as cases where IRT contacts were made by the site either prematurely or 


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inappropriately prior to confirmation of the subject’s final randomization eligibility and no 
study medication was administered to the subject. 
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, where treatment received is defined 
as the randomized/assigned treatment if the subject took at least one dose of that treatment or 
the first treatment received if the randomized/assigned treatment was never received. 
The summary statistics analyses in this study will be performed according to domains with 
respective specifications of analyses sets, analyses period and treatment groups (Table 2-1). 
Table 2-1 
Summary statistics specifications  
Domains 
Analyses 
sets 
Analysis Period 
Treatment group labels for each 
analysis period 
Patient disposition, 
Demographics, Other baseline 
characteristics* 
RAS 
Treatment Period 1 
 
Secukinumab 300 mg Q4W 
Placebo 
Total 
Treatment Period 2 
Follow up (only for 
disposition tables) 
 
Secukinumab 300 mg Q4W 
Secukinumab 300 mg Q2W 
Total 
Efficacy endpoints 
FAS 
Treatment Period 1 
 
Secukinumab 300 mg Q4W 
Placebo 
Entire 
treatment 
period 
Secukinumab 300 mg Q4W 
Placebo 
Placebo-Secukinumab 300 mg Q2W 
Safety data (Number of doses, 
duration of exposure, prior 
and concomitant therapies, 
concomitant medical 
procedures, significant non-
drug therapies, laboratory 
data, AEs, etc.) 
Safety set  
Treatment Period 1 
Secukinumab 300 mg Q4W 
Placebo 
Entire 
treatment 
period 
Secukinumab 300 mg Q4W 
Secukinumab 300 mg Q2W 
Placebo 
Any Secukinumab 
* Treatment groups for protocol deviations for entire treatment period: AIN457 300 mg Q4W, AIN457 300 mg 
Q2W, Any AIN457 300 mg, Placebo, Total 
 
2.2.1 
Subgroup of interest 
The efficacy endpoints will be evaluated by subgroups in an RShiny app. Subgroups of interest 
may include gender, age, Hepatitis C infection, weight, smoking history, previous systematics 
therapy for lichen planus, time since diagnosis, baseline IGA score and oral/genital affection in 
MLP.  


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2.3 
Patient 
disposition, 
demographics 
and 
other 
baseline 
characteristics 
The analyses of patient disposition, demographics and other baseline characteristics will be 
based on the randomized set. 
Summary analyses in this section 2.3 will be shown by treatment groups as specified in Table 
2-1. 
2.3.1 
Patient disposition 
The number of subjects screened will be presented. In addition, the reasons for screen failures 
will be provided. The number and percentage of subjects in the randomized set who completed 
Treatment Period 1, Treatment Period 2 and Follow up Period, and who discontinued the study 
prematurely (including the reason for discontinuation) will be presented by study period for 
each treatment group. 
For each protocol deviation, the number and percentage of subjects for whom the deviation 
applies will be tabulated by treatment group. 
2.3.2 
Demographics and other baseline characteristics 
Common background and demographic variables will be analyzed in the randomized set.  
For three lichen planus subtype cohorts (predominant subtype), summary statistics for these 
variables will be analyzed for each cohort (Section 2.1) and for each treatment group (Table 2-
1) according to the type of variables as continuous or discrete. Summary statistics could be 
analyzed across three cohorts. 
Lichen planus specific baseline characteristics and history of disease will be summarized for 
three cohorts (predominant subtypes) as follows.   
Table 2-2 
Demographics and other baseline characteristics 
Variable(s) 
Cohorts applied 
Demographics 
Continuous 
CLP, MLP, LPP, 
All 
Age  
Height 
Weight 
Body mass index (BMI) 
Categorical 
Age categories (<65 years, 65 years and older) 


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Variable(s) 
Cohorts applied 
Gender 
Race 
Ethnicity 
Smoking status at baseline 
Lichen planus specific baseline characteristics 
Continuous 
Patient Assessment of Itch (by each of the three questions) 
CLP, MLP, LPP,  
All 
Patient Assessment of Pain (by each of the three questions) 
Dermatology Life Quality Index (DLQI) 
Time since diagnosis of predominant lichen planus 
Reticular Erythematous Ulcerative score (REU) 
MLP 
Oral Lichen Planus Symptom Severity Measure (OLPSSM) 
MLP 
Lichen Planopilaris Activity Index (LPPAI) 
LPP 
Scalpdex 
LPP 
Categorical  
IGA score (at least  moderate and severe) 
CLP, MLP, LPP, 
All 
Hepatitis C infection 
Previous exposure to biological systemic medication for lichen 
planus (yes, no) 
Previous exposure to non-biologic systemic medication for lichen 
planus (yes, no) 
Current use of topical medications (excluding ultrahigh or high 
potency  corticosteroids, as per WHO classification) (yes, no) 
Percentage of patients with concomitant MLP 
CLP 
Baseline IGA score of concomitant MLP (at least mild, moderate, 
and severe) 
CLP 
Anatomical location of concomitant MLP (Oral, Genital, 
Esophageal) 
CLP, MLP, All 
Percentage of patients with concomitant CLP 
MLP 
Baseline IGA score of concomitant CLP (at least mild, moderate, 
and severe) 
MLP 
 
Body Mass Index (BMI) will be calculated using the following formula: 
BMI = (body weight in kilograms) / (height in meters)2 
For BMI, height and body weight of the last value prior to first dose will be used as a baseline 
value. If there is no weight or height recorded prior to taking the study treatment, BMI will be 
missing.  
Time since diagnosis of the lichen planus (predominant subtypes) will be calculated using the 
following formula: 
• Time since diagnosis of predominant lichen planus= (inform consent date – diagnosis 
date of the predominant lichen planus (from medical history CRF page) + 1)/365.25 
Any condition entered on the relevant medical history / current medical conditions CRF will be 
coded using the MedDRA dictionary. They will be summarized by System Organ Class (SOC) 
and Preferred Term (PT) of the MedDRA dictionary. 


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2.4 
Treatments (study treatment and concomitant medications) 
The analysis of study treatment data will be based on the safety set. 
2.4.1 
Study treatment / compliance 
The number of secukinumab and placebo injections doses will be summarized for Treatment 
Period 1 and entire treatment period by treatment group using contingency tables as specified 
in Table 2-1. 
The duration of exposure to study treatment will be summarized as the number of subjects with 
exposure of at least certain time thresholds, displayed using the following categories: “any 
exposure”, “≥1 week”, “≥2 week”, “≥3 week” , “≥4 weeks”, “≥8 weeks”, “≥12 weeks”, “≥16 
weeks”, “≥24 weeks”, “≥32 weeks. The results will be presented by analyses periods and 
treatment groups as specified in Table 2-1. 
Duration of exposure will be defined as the time from first dose of study medication to the last 
dose plus 84 days or last visit (including follow-up visits) whichever occurs earlier. For subjects 
who discontinued or have their last visit earlier than last dose plus 84 days, the end of study 
treatment exposure will be the date of the last study visit in the follow-up period or in the 
corresponding treatment period. 
Duration of exposure (days) = min (“end of study” date, last dose date +84) – first dose date +1 
Duration of exposure (years) = duration of exposure (days) / 365.25 
2.4.2 
Visit windows 
Visit windows will be used for the data that is summarized by visit; they are based on the study 
evaluation schedule and comprise a set of days around the nominal visit day. For any assessment, 
there are protocol defined scheduled visits around which visit windows were created to cover 
the complete range of days within the study. For subjects randomized to Placebo group to 
secukinumab 300 mg every 2 weeks arm, the day of taking the first secukinumab dose will also 
need to be taken into visit window consideration. The visit windows are shown in Table 2-3. In 
this table, the days are counted since the first dose of study treatment (study days) for safety 
assessments and the days are counted since the date of randomization for efficacy assessments. 
These visit windows apply to measurements taken at every visit. For assessments collected less 
often different visit windows will be applied as detailed below. 
When visit windows are used, all visits will be re-aligned, i.e. they will be mapped into one of 
the visit windows. E.g., if the Week 4 visit of a subject is delayed and occurs on Day 60 instead 
of on Day 29, it will be re-aligned to visit window Week 8. 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 in Section 2.4.3. 


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Table 2-3 
Assessment windows for scheduled visits 
Analysis Visit 
Week 
Scheduled Day 
Visit Window 
Baseline 
BSL 
1 
-28 days to Day 1* 
Week 2 
2 
15 
Day 2-22 
Week 4 
4 
29 
Day 23-43 
Week 8 
8 
57 
Day 44-71 
Week 12 
12 
85 
Day 72-99 
Week 16 
16 
113 
Day 100-127 
Week 20 
20 
141 
Day 128-155 
Week 24 
24 
169 
Day 156-183 
Week 28 
28 
197 
Day 184-211 
Week 32 
32 
225 
Day 212-239 
Week 36 
36 
253 
Day 240-267 
Week 40 
40 
281 
Day 268-295 
* Day 1 is the date of the first drug administration for safety assessments and the date of the 
randomization for efficacy assessments. 
 
For parameters which are not collected at every visit (e.g. laboratory, Lichen Planopilaris 
Activity Index), visit windows defined in Table 2-3 will be combined. The following rules are 
used to determine the visit window for an applicable visit post baseline: “Lower limit” = “upper 
limit of prior applicable visit” + 1. “Upper limit” = “target day of current visit” + integer part 
of (“target day of next applicable visit” – “target day of current visit”)/2. For example, if a 
parameter is measured at Week 12 and Week 28 only, Week 12 visit window will extend from 
Day 2 to Day 141 (combining Week 1 to Week 20 visit windows), Week 28 will extend from 
Day 142 to Day 295 (combining Week 21 to Week 40). If more than one assessment falls into 
the interval, the rules defined in Section 2.4.3 below are applied. 
The analysis visit will be used for listing of visit and period for both safety and efficacy data. If 
a visit falls after the last visit window (after Day 295) it is not assigned an analysis visit and 
will be listed under label “After Week 40”. 
2.4.3 
Multiple assessments within visit windows 
When there are multiple assessments in a particular visit window, the following rules are applied 
to select one value “representing” the subject in summary statistics in a visit window (Table 2-
4).  
For baseline assessment definition, see Section 2.1.1.2. For post-baseline visit windows the 


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following applies (unless otherwise specified): 
• for quantitative variables, the closest to the actual visit is chosen (if two assessments have 
the same distance, then the earlier one will be chosen);  
• in case qualitative variables are based on quantitative variables, the visit will be assigned to 
the quantitative variable, and this visit will be used for the derived qualitative variable.  
Table 2-4 
Rules for selecting values for analysis within a given visit window  
Timing 
of 
measurement 
Type of data 
Rule 
Baseline 
All data 
See Section 2.1.1.2 
Post-baseline 
efficacy 
All data except for PRO 
(e.g., IGA) 
The measurement closest to the target day will be used. 
In the event two measurements are taken equally apart 
(e.g., 1 day before target date and 1 day after), the 
results from the earlier visit will be used. 
If two measurements are taken on the same day, then 
select the first one using eCRF visit number. 
If two measurements have been taken on the same day 
and same visit then select the worst. 
PRO data 
The measurement closest to the target day will be used. 
In the event two measurements are taken equally apart 
(e.g., 1 day before target date and 1 day after), the earlier 
one will be used.  
If two measurements have been taken on the same day, 
select the worst. 
If two measurement have the same value, select the first 
one using eCRF visit number. 
Post-baseline 
safety 
Summary 
visit 
information 
(e.g. 
laboratory values, vital 
signs, etc.) 
The (non-missing) measurement closest to the target day 
will be used.  
In the event two measurements are taken equally apart 
(e.g. 1 day before target date and 1 day after) the first 
one will be used.  
If two measurements are taken on the same day then 
select the first one (using the time). 
If two measurements are taken on the same date/time 
then use the first visit number (assuming this is the 
planned visit). 
If two measurements are taken on the same 
date/time/eCRF visit number then use the average of two 
assessments. 
Post-baseline 
safety  
Notable 
abnormalities 
for laboratory values 
The most extreme measurement in the window will be 
used. Note this means a subject can have a notably high 
and notably low measurement within an analysis period. 
2.4.4 
Prior, concomitant and post therapies 
Medications will be identified using Novartis Drug and Therapy Dictionary (NovDTD) 
including Anatomical Therapeutic Chemical (ATC) code. Prior and concomitant treatments will 
be summarized by Treatment Period 1 and entire treatment period and by respective treatment 
groups (Table 2-1).  


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Prior medications are defined as drugs taken and stopped prior to the first dose of study 
treatment. Any medication given at least once between the day of first dose of study treatment, 
and within 84 days after last dose will be a concomitant medication, including those that were 
started before first dose of study treatment and continued into the Treatment Period.  
Prior or concomitant medication will be identified based on recorded or imputed start and end 
dates of medication taken (see Section 5.1.3).  
Medications will be presented in alphabetical order, by ATC codes and grouped by anatomical 
main group (the 1st level of the ATC codes). Tables will also show the overall number and 
percentage of subjects receiving at least one drug of a particular ATC code and at least one drug 
in a particular anatomical main group.  
In addition, medical procedures and significant non-drug therapies as coded in MedDRA will 
be summarized. 
2.5 
Analysis of the primary objective 
The primary aim of the study is to demonstrate the efficacy of secukinumab (300 mg Q4W) 
with respect to IGA responder status after 16 weeks of treatment compared to placebo. 
2.5.1 
Primary endpoint 
The primary endpoint of the study is the proportion of IGA responders within each cohort at 
Week 16, where IGA response is defined as achieving an absolute IGA score less than or equal 
to 2. Each cohort (CLP, MLP and LPP) of the study will have its own primary efficacy endpoint 
analyzed separately.  
The analysis of the primary endpoint will be based on the FAS. 
2.5.2 
Statistical hypothesis, model, and method of analysis 
The primary endpoint of IGA response at Week 16 is a binary (yes/no) outcome; it will be 
analyzed by a Bayesian method based on the Beta-Binomial model. Bayesian inference based 
on the non-informative prior of Beta (1/3, 1/3) for each treatment group will be used to obtain 
the posterior distribution of the treatment difference between secukinumab and placebo for the 
three subtypes, respectively.  
The Bayes PoC criteria to be assessed for the primary endpoint are: 
1) the posterior probability of the treatment difference greater than zero (δ>0) is greater than 
90%;  
Pr (δ (secukinumab, placebo) > 0 | data) > 90% and 
2) the posterior probability of the treatment difference exceeding half of the target effect of 0.30 
(δ>0.15) is greater than 50% 
Pr (δ (secukinumab, placebo) > 0.15 | data) > 50% 
where δ denotes the treatment difference between secukinumab and placebo with respect to the 


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IGA response at Week 16. 
Bayesian model 
The statistical model used will include a fixed factor for treatment (secukinumab or placebo). 
It is assumed that the number of responder patients is a random variable following a binomial 
distribution Binomial (nk, pk) where nk is the sample size and pk is the true underlying proportion 
of responder patients. Given the prior of Beta (1/3, 1/3) for each treatment group, the posterior 
of pk is also a Beta distribtion as following: 
pk |sk ~Beta(1/3+sk, 1/3+nk-sk) 
where sk is the observed number of patients who have responded among the nk patients observed. 
Estimates of the posterior probabilities of the difference of the IGA responder rate between the 
secukinumab 300 mg treatment and placebo groups at Week 16 will be presented together with 
two sided 95% credible intervals (2.5% to 97.5%). Estimates of the posterior probabilities of 
the efficacy criteria (criteria 1 and 2) being met will be provided. 
The posterior beta density function of the estimated proportion of responders will be displayed 
graphically.  
2.5.3 
Handling of missing values/censoring/discontinuations. 
Subjects who discontinue treatment before Week 16 will be considered failures (i.e., non-
responder). Missing values not related to treatment discontinuation will be analyzed as observed. 
2.5.4 
Supplementary analyses 
Two supplementary analyses are planned. 
2.5.4.1 
Hypothetical strategy 
A supplementary analysis will evaluate the treatment effect assuming that patients would not 
discontinue study drug for the intended duration of 16 weeks (hypothetical strategy). Data after 
study treatment discontinuation will be replaced by multiple imputed data using the MAR 
(missing at random) assumption. Detail information could be found in the Estimand charter 
(Section 5.4 and Section 5.5.2). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2.6 
Analysis of secondary objectives 
2.6.1 
Secondary endpoints 
Secondary efficacy endpoints will be analyzed separately for each independent cohort (CLP, 
MLP, LPP) or for one specific cohort, as specified in Table 2-5. Treatment groups for summary 
statistics are summarized in Table 2-1. 
 
 
• Endpoints for each independent cohort 
Investigator’s Global Assessment (IGA)  
The following IGA related endpoints are considered: 
• IGA ≥2 points improvement response: defined as achieving an ≥2 IGA score 
decreasing compared with baseline (thus at least achieving an IGA score of ≤ 2).  
• IGA 0 or 1 response: defined as achieving an IGA score of 0 or 1 (thus at least 
achieving an IGA ≥2 points improvement) 
For IGA ≥2 points improvement response and IGA 0 or 1 response from Week 1 to Week 16, 
comparisons between the 300 mg Q4W treatment regimen and placebo groups will be 
conducted using the Fisher exact test. Estimates of the difference of response rates between the 
300 mg Q4W treatment regimen and placebo groups together with 95% confidence intervals 
will be presented. 


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Summary statistics for IGA ≥2 points improvement and IGA 0 or 1 response by visit from 
baseline up to the end of study for each treatment group will be presented in contingency tables 
with the number and percentage of subjects in each category.  
Dermatology Life Quality Index  
Seven scores will be derived from the DLQI: the total score of each of the six dimensions and 
the total score over all items. The higher the score, the more quality of life is impaired. The 
DLQI total score over all items will be calculated by summing the score of each question 
resulting in a maximum score of 30 and a minimum score of 0.  
For the total DLQI score and each of the seven total item scores, summary statistics will be 
provided for the absolute and percentage change from baseline by visit up to the end of study 
for each treatment group. 
Achievement of DLQI total score of 0 or 1 among subjects with baseline DLQI score ≥2 will 
be considered as a DLQI 0/1 responder. The number and proportion (%) of DLQI responders 
will be presented by visit up to the end of study for each treatment group. Between-treatment 
differences for the proportion of DLQI responder from Week 1 to Week 16 together with 95% 
confidence intervals will be presented. 
Patient Assessment of Itch (NRS) 
Itch is assessed with three questions about an overall severity, severity at the worst moment and 
the overall degree of bother, respectively. Each of the question will be answered using a numeric 
rating scale (NRS, ranging from 0 to 10).  
For each of the three questions, summary statistics will be provided for the absolute and 
percentage change from baseline by visit up to the end of study for each treatment group.  
Patient Assessment of Pain (NRS) 
Pain is assessed with three questions, each answered using a numeric rating scale (NRS, ranging 
from 0-10).  
For each of the three questions, summary statistics will be provided for the absolute and 
percentage change from baseline by visit up to end of study for each treatment group.  
 
• Endpoint for CLP 
Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease 
PSAD evaluates the extent of cutaneous lesions. PSAD ranges from 0 to 5, with lower scores 
corresponding to lower percentages of surface area with disease.  
The number and percentage of subjects in each category will be presented by visit up to the end 
of study for each treatment group.  
 
• Endpoints for MLP 


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Reticular erythematous Ulcerative (REU) score 
The REU score was developed as a semi-quantitative scale, measuring disease severity based 
on 3 dimensions: reticulation, erythema and ulceration. Scores for each of the 3 clinical 
dimensions will add up to a total weighted score (REU score).  
Summary statistics for the REU score will be provided for absolute and percentage change from 
baseline by visit up to end of study for each treatment group.  
Oral Lichen Planus Symptom Severity Measure (OLPSSM) 
OLPSSM was a PRO-based assessment of the symptom experience of subjects with oral lichen 
planus in clinical studies, ranging from 0 to 28, with higher scores indicating worse severity. 
Summary statistics will be provided for absolute and percentage change from baseline of 
OLPSSM score by visit up to end of study for each treatment group. 
 
• Endpoints for LPP 
LPP Activity Index (LPPAI)  
LPPAI is a numeric score to quantify the signs and symptoms of LPP (Chiang, 2010). Subjects 
with an LPPAI reduction greater than 85% over pretreatment values were considered 
responders, with 25% to 85% reduction were considered partial responders, and with less than 
25% reduction were considered non-responders.  
Summary statistics will be provided for absolute and percentage change from baseline of LPPAI 
score by visit up to the end of study for each treatment group. 
The number and proportion of LPPAI responders and partial responders will be presented by 
visit up to the end of study for each treatment group.  
Scalpdex 
Scalpdex is a self-administered, health-related quality of life instrument originally developed 
for scalp dermatitis. This survey includes 23 items, each item scored on a scale of 0-100, where 
0=never, 25=rarely, 50=sometimes, 75=often and 100=all the time. The 23 items are mapped 
into 3 major domains that affect patient quality of life: symptoms, functioning, and emotions. 
The Scalpdex will be evaluated both as a total score, calculated as the mean of all 23 items, and 
by 3 dimensions, calculated as the mean of the item scores pertaining to each domain (Chen, 
2002). 
Summary statistics will be provided for absolute and percentage change from baseline 
of Scalpdex total score and scores of 3 domains by visit up to end of study for each treatment 
group. 


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Table 2-5 
Overview of analysis methods for secondary efficacy variables 
Variable(s) 
Cohorts 
applied 
Summary 
statistics for 
discrete data 
Statistical 
analyses 
Summary 
statistics for 
continuous 
data 
Graphs* 
IGA response over timea 
CLP, MLP, 
LPP 
X 
Fisher exact 
test @ Week 
1- 16 
 
X 
DLQI 0/1 response over 
time 
CLP, MLP, 
LPP 
X 
 
 
X 
DLQI total score and item 
score overtime 
CLP, MLP, 
LPP 
 
 
X 
Xb 
Patient Assessment of Itch 
(NRS) 
over 
time 
(3 
questions) 
CLP, MLP, 
LPP 
 
 
X 
 
Patient Assessment of Pain 
(NRS) 
over 
time 
(3 
questions) 
CLP, MLP, 
LPP 
 
 
X 
 
PSAD over time 
CLP 
X 
 
 
Xc 
 
REU over time 
MLP 
 
 
X 
Xd 
OLPSSM over time 
MLP 
 
 
X 
 
LPPAI 
responder 
and 
partial responder over time 
LPP 
X 
 
 
 
LPPAI score over time 
LPP 
 
 
X 
Xd 
Scalpdex over time 
LPP 
 
 
X 
 
*Line plots. The graphs may only be presented in the Rshiny app where appropriate. 
aIGA responses include: 1) IGA ≥2 points improvement response and 2) IGA= 0 or 1 response.  
bTotal DLQI score change from baseline by cohort.  
cPloted as a categorical variable. 
dTime course of percent change from baseline. 
 
2.6.2 
Statistical hypothesis, model, and method of analysis 
Not applicable 
2.6.3 
Handling of missing values/censoring/discontinuations 
Data collected after treatment discontinuation by Week 32 will be replaced with the baseline 
value of the patients for all secondary endpoints above. Missing values not related to treatment 
discontinuation will be analyzed as observed. 
2.7 
Analyses of safety endpoints 
All safety analyses will be based on the safety set. Only those visits that were pre-planned in 
the protocol will be reported in tables for safety variables. 
Analysis of adverse events will be based on treatment emergent events, which are defined as 
events started on or after the first dose of study treatment or events present prior to the first dose 
of study treatment but increased in severity based on preferred term and on or before last dose 
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Other safety variables including LAB, Vitals will be evaluated based on on-treatment events, 
which are defined as any events that happened after first dose of study treatment and on or 
before last dose +84 days. 
Safety analysis will be performed on actual treatment, for patients in any of the three cohorts 
and in each of the three cohorts, respectively. Analyses will be presented by Treatment Period 
1 and entire treatment period and by treatment groups as specified in Table 2-1.  
2.7.1 
Adverse events (AEs) 
For adverse events and other binary safety variables, crude incidences and exposure-adjusted 
incidence rate (EAIR) will be derived as described below and summarized in Table 2-6. The 
crude incidence of treatment emergent adverse events will be summarized by primary SOC and 
PT.  
All AEs and serious adverse events (SAEs) will be listed with “treatment emergent” flag 
displayed. 
Table 2-6 
Overview of analyses on some safety endpoints 
Analysis 
period 
AEs &  
SPP risks 
SAEs 
AEs 
by 
severity 
Study 
treatment 
related AEs, death & 
other significant AEs 
Notables 
(lab/vitals) 
Treatment 
Period 1  
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude incidence 
• crude incidence 
Entire study 
period 
• crude 
incidence 
• exposure-
adjusted 
incidence rate 
• crude 
incidence 
• exposure-
adjusted 
incidence rate 
• crude 
incidence 
 
• crude incidence 
• exposure-adjusted 
incidence rate 
 
• crude incidence 
AEs will be summarized by presenting, for each cohort and each treatment group, the number 
and percentage of subjects having at least one AE, having at least one AE in each primary SOC 
and having each individual AE (preferred term). Summaries will also be presented for AEs by 
severity. If a particular AE ‘severity’ is missing, this variable will be listed as missing and 
treated as missing in summaries. If a subject reported more than one AE with the same PT, the 
AE with the greatest severity will be presented. If a subject reported more than one AE within 
the same primary SOC, the subject will be counted only once with the greatest severity at the 
SOC level, where applicable. AEs by severity will be provided by SOC and AEs by severity 
and PTs may be provided if required at ad-hoc basis. 
The most common AEs reported (at least two cases in any treatment group by SOC and PT) 
will be presented in descending frequency according to its incidence in AIN457 300 mg Q4W 
group starting from the most common event. Here the threshold value is set to at least two cases 
in any treatment group by PT but it may be updated. 
Separate summaries will be provided for deaths, SAEs, and other significant AEs leading to 
discontinuation. 
For the legal requirements of ClinicalTrials.gov and EudraCT, two required tables on treatment 
AEs which are not SAEs with an incidence greater than 5% and on treatment SAEs and SAE 


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suspected to be related to study treatment will be provided by SOC and PT on the safety set 
population.  
If for a same patient, several consecutive AEs (irrespective of study treatment causality, 
seriousness and severity) occurred with the same SOC and PT: 
• a single occurrence will be counted if there is  ≤ 1 day gap between the end date of the 
preceding AE and the start date of the consecutive AE 
• more than one occurrence will be counted if there is > 1 day gap between the end date 
of the preceding AE and the start date of the consecutive AE 
For occurrence, the presence of at least one SAE / SAE suspected to be related to study 
treatment / non SAE has to be checked in a block e.g., among AE's in a ≤ 1 day gap block, if at 
least one SAE is occurring, then one occurrence is calculated for that SAE. 
Algorithms for AE date imputations will be provided in Section 5.1.2. 
2.7.2 
Deaths 
Separate summary and listing will be provided for deaths. The number of deaths resulting from 
SAEs suspected to be related to study treatment and SAEs irrespective of study treatment 
relationship will be provided by SOC and PT. 
2.7.3 
Laboratory data 
The summary of laboratory evaluations will be presented for two groups of laboratory tests 
(hematology and serum chemistry). Descriptive summary statistics for the change from baseline 
to each study visit will be presented. These descriptive summaries will be presented by cohort, 
test group, laboratory test and treatment group. Change from baseline will only be summarized 
for subjects with both baseline and post baseline values. In addition, Summary of notable 
abnormalities of key laboratory tests will be provided by treatment group. Detail on notable 
abnormalities derivations will be specified in Section 5.3. 
2.7.4 
Other safety data 
2.7.4.1 
Vital signs 
Analysis of the vital sign measurements using summary statistics for the change from baseline 
for each post-baseline visit will be performed. These descriptive summaries will be presented 
by cohort, vital sign and treatment group. Change from baseline will only be summarized for 
subjects with both baseline and post-baseline values. 
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 2-7 below. A listing 
of subjects with newly occurring notably abnormal vital signs will be provided. 


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Table 2-7 
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 
 
2.9 
PD and 
/PD analyses 
The 
 other clinically important 
endpoints, such as PSAD, REU, LPPAI will be investigated if appropriate. 
2.11 
Patient-reported outcomes 
Please refer to Section 2.6 and Section 2.13 for the analysis method of Patient-reported 
outcomes. 


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2.14 
Interim analysis 
Primary endpoint analysis will be performed after all subjects have completed Week 16 visit.  
Additional analyses may be performed to support health authority interactions as necessary. 
At the End of Study, a final analysis will be performed when all subjects have completed the 


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last study visit. 
3 
Sample size calculation 
Total sample size planned for this study is 108 with 36 subjects in each subtype. 
For each subtype, 24 secukinumab 300 mg Q4W treatment regimen subjects and 12 placebo 
subjects assures the 71% probability to claim positive PoC results, based on the assumptions 
that the placebo IGA responder rate is 20% and secukinumab 300 mg Q4W placebo difference 
(delta) of the IGA responder rates is at least 30%. 
For different response rate assumptions on the secukinumab 300 mg Q4W and placebo dose 
regimens, Figure 3-1 and Table 3-1 reported below show that there is no substantial difference 
in the probability of claiming a successful PoC results between randomization ratios 1:1 and 
2:1. Considering the absence of previous lichen planus secukinumab data, randomization 2:1 is 
chosen for this study, to assure the collection of more efficacy and safety data on lichen planus 
secukinumab subjects, while limiting the number of subjects exposed to placebo. Figure 3-1 
and Table 3-1 also show that the probability of claiming positive PoC results being around 70% 
when the secukinumab 300 mg Q4W and placebo difference (delta) of the IGA responder rates 
is 30% in any scenario, and greater than 85% when the secukinumab 300 mg Q4W and placebo 
difference (delta) of the IGA responder rates is 40% in any scenario. 
Figure 3-1 
Operating Characteristics on different randomization ratio and different 
response rate assumption 
  


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Table 3-1 
Operating Characteristics on different randomization ratio and different 
response rate assumption 
Secukinumab response 
rate 
Placebo response rate 
Probability to meet target 
efficacy with AIN 18: 
PBO 18 
Probability to meet target 
efficacy with AIN 24: 
PBO 12  
A(small)=0.4 
0.1 
0.838 
0.793 
B(moderate)=0.5 
0.1 
0.945 
0.923 
C(high)=0.6 
0.1 
0.987 
0.978 
D(very high)=0.7 
0.1 
0.998 
0.996 
E(extreme high)=0.8 
0.1 
1.000 
1.000 
A(small)=0.4 
0.2 
0.543 
0.503 
B(moderate)=0.5 
0.2 
0.767 
0.712 
C(high)=0.6 
0.2 
0.915 
0.871 
D(very high)=0.7 
0.2 
0.980 
0.960 
E(extreme high)=0.8 
0.2 
0.998 
0.993 
A(small)=0.4 
0.3 
0.282 
0.255 
B(moderate)=0.5 
0.3 
0.520 
0.454 
C(high)=0.6 
0.3 
0.751 
0.675 
D(very high)=0.7 
0.3 
0.908 
0.856 
E(extreme high)=0.8 
0.3 
0.980 
0.961 
*Calculation for Operating Characteristics was based on QTD version 3.0.0 


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5 
Appendix 
5.1 
Imputation rules 
5.1.1 
Study drug 
Any partial dates will be imputed as follows: 
The earlier day will be taken from below 
• The last day in the month and  
• The end day of the corresponding Treatment Period 
5.1.2 
AE date imputation 
Impute AE end date: 
1. If the AE end date ‘month’ is missing, the imputed end date should be set to the earliest of 
the (min (last visit date, last dose date + 84 days), 31DECYYYY, date of death).  
2. If the AE end date ‘day’ is missing, the imputed end date should be set to the earliest of the 
(min (last visit date, last dose date + 84 days), last day of the month, date of death).  
3. If AE ‘year’ is missing or AE is ongoing, the end date will not be imputed.  
Impute AE start date:  
Before imputing AE start date, find the AE start reference date.  
1. If the (imputed) AE end date is complete and the (imputed) AE end date < treatment start 
date then AE start reference date = min(informed consent date, earliest visit date).  
2. Else AE start reference date = treatment start date  
1. If the AE start date ‘year’ value is missing, the date uncertainty is too high to impute a rational 
date. Therefore, if the AE year value is missing, the imputed AE start date is set to NULL.  
2. If the AE start date ‘year’ value is less than the treatment start date year value, the AE started 
before treatment. Therefore:  
a. If AE ‘month’ is missing, the imputed AE start date is set to the mid-year point 
(01JULYYYY).  
b. Else if AE ‘month’ is not missing, the imputed AE start date is set to the mid-month 
point (15MONYYYY).  
3. If the AE start date year value is greater than the treatment start date year value, the AE 
started after treatment. Therefore:  
a. If the AE month is missing, the imputed AE start date is set to the year start point 
(01JANYYYY).  
b. Else if the AE month is not missing, the imputed AE start date is set to the later of 


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(month start point (01MONYYYY), AE start reference date + 1 day).  
4. If the AE start date year value is equal to the treatment start date year value:  
a. And the AE month is missing the imputed AE start date is set to the AE reference 
start date + 1 day.  
b. Else if the AE month is less than the treatment start month, the imputed AE start date 
is set to the mid-month point (15MONYYYY).  
c. Else if the AE month is equal to the treatment start date month or greater than the 
treatment start date month, the imputed AE start date is set to the later of (month start 
point (01MONYYYY), AE start reference date + 1 day).  
If complete (imputed) AE end date is available and the imputed AE start date is greater than the 
(imputed) AE end date, then imputed AE start date should be set to the (imputed) AE end date. 
5.1.3 
Concomitant medication date imputation 
Impute CM end date:  
1. If CM end day is missing and CM month/year are non-missing then impute CM day as the 
minimum of treatment end date and the last day of the month.  
2. If CM end day/month are missing and CM year is non-missing then impute CM day as the 
minimum of treatment end date and the end of the year (31DECYYYY).  
3. If imputed CM end date is less than the CM start date, use the CM start date as the imputed 
CM end date.  
Impute CM start date:  
1. If the CM start date year value is missing, the imputed CM start date is set to one day prior 
to treatment start date.  
2. If the CM start date year value is less than the treatment start date year value, the CM started 
before treatment. Therefore:  
a. If the CM month is missing, the imputed CM start date is set to the mid-year point 
(01JULYYYY).  
b. Else if the CM month is not missing, the imputed CM start date is set to the mid-
month point (15MONYYYY).  
3. If the CM start date year value is greater than the treatment start date year value, the CM 
started after treatment. Therefore:  
a. If the CM month is missing, the imputed CM start date is set to the year start point 
(01JANYYYY).  
b. Else if the CM month is not missing, the imputed CM start date is set to the month 
start point (01MONYYYY).  
4. If the CM start date year value is equal to the treatment start date year value:  
a. And the CM month is missing or the CM month is equal to the treatment start date 
month, then the imputed CM start date is set to one day prior treatment start date.  
b. Else if the CM month is less than the treatment start date month, the imputed CM start 
date is set to the mid-month point (15MONYYYY).  
c. Else if the CM month is greater than the treatment start date month, the imputed CM 
start date is set to the month start point (01MONYYYY).  


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If complete (imputed) CM end date is available and the imputed CM start date is greater than 
the (imputed) CM end date, then imputed CM start date should be set to the (imputed) CM end 
date.  
5.1.4 
Medical history date imputation 
1. If the medical history date day/ month are missing and the year is non-missing: 
a. If the year part of the date is equal to the year part of the inform consent date, 
then the imputed date is set to the year start point (01JANYYYY). 
b. Otherwise the imputed date is set to the mid-year point (01JULYYYY). 
2. If the medical history day is missing and the month/year are non-missing: 
a. If the month and year part of date is equal to the month and year part of the 
inform consent date, then the imputed date is set to the month start point 
(01MONYYYY). 
b. Otherwise the imputed date is set to the mid-month point (15MONYYYY). 
5.1.5 
Other imputations 
For laboratory test values below Lower Level of Quantification (LLQ) or above Upper Level 
of Quantification (ULQ) will be imputed as LLQ or ULQ value, respectively. The numerical 
part of the reported result will be treated as the actual LLQ or ULQ. These laboratory values 
will be displayed in listings using the standard unit with the reported sign (“<” or “>”).” 
5.2 
AEs coding/grading 
AEs will be coded according to MedDRA dictionary. The MedDRA version used for reporting 
the adverse events will be described in a footnote. 
5.3 
Laboratory parameters derivations 
The following criteria will be used to define expanded limits and clinically notable 
abnormalities of key laboratory tests. 
Liver Function and Related Variables 
Alanine transaminase (ALT) (SGPT): > 3 x Upper Limit of Normal (ULN) 
Aspartate transaminase (AST) (SGOT): > 3 x ULN 
Total bilirubin: > 2 x ULN 
Alkaline phosphatase: > 2.5 x ULN 
Renal Function 
Creatinine (serum): > 1.5 x ULN 


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Hematology 
Hemoglobin: ≥ 20 g/l decrease from baseline 
Platelet count: < Lower Limit of Normal (LLN) 
White blood cell count: < 0.8 x LLN 
Neutrophils: < 0.9 x LLN 
Eosinophils: > 1.1 x ULN 
Lymphocytes: > 1.1 x ULN 
5.4 
Estimand Charter 
5.4.1 
Introduction 
Secukinumab is being explored as a treatment for lichen planus, and studied in subjects with 
biopsy-proven forms of lichen planus not adequately controlled with topical therapies in the 
proof of concept trial CAIN457S12201.  
This section describes the estimands and corresponding estimation procedures for the primary 
endpoint, in line with the latest discussions of the forthcoming ICH E9 (R1) addendum.  
An estimand defines in detail what needs to be estimated to address a specific scientific question 
of interest. A description of an estimand includes five attributes:   
• The population, that is, the patients targeted by the scientific question; 
• The variable (or endpoint), to be obtained for each patient, that is required to address 
the scientific question; 
• The treatment of interest. The test treatment of interest and the control treatment to 
which comparison will be made (if applicable). 
• The specification of how to account for intercurrent events to reflect the scientific 
question of interest; 
• The population-level summary for the variable that provides, as required, a basis for a 
comparison between treatment conditions. 
This section focuses in particular on the management of intercurrent events (for example, 
discontinuation of assigned treatment, use of an additional or alternative therapy). Other aspects 
of the estimand like the population, the variable, the treatment of interest and the population-
level summary for the variable are presented, but are not the focus of this document. 
5.4.1.1 
Purpose of the CAIN457S12201 study 
The purpose of this proof of concept study is to explore the efficacy of secukinumab in the 
treatment of adult patients with biopsy-proven lichen planus not adequately controlled with 
topical therapies, and to assess the safety and tolerability over 32 weeks. The primary objective 


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of the study is to demonstrate the efficacy of secukinumab (300 mg Q4W) with respect to IGA 
response (i.e., achievement of IGA score ≤ 2) after 16 weeks of treatment compared to placebo. 
5.4.1.2 
Different types of intercurrent events 
1. Changes in the dose of allowed concomitant medications for topical therapy: patients 
entering the trial are not allowed to use any topical therapies except for the allowed 
concomitant topical medications (described in Section 6.2.1 of the protocol). Patients 
must have reached a stable dose and application frequency of these allowed topical 
treatments at least 2 weeks prior to randomization and the administration should remain 
stable regarding dose and application frequency during first 16 weeks treatment. 
2. Other concomitant medications: medications that are not explicitly prohibited by the 
protocol (e.g., antibiotics or NSAIDs, or supplements). 
3. Prohibited medications: medications that are prohibited by the protocol (described in 
Section 6.2.2 of the protocol) and that have a potential confounding effect on the 
efficacy of secukinumab (e.g. immunosuppressive agents such as methotrexate, 
cyclosporin or systemic glucocorticoids). 
4. Discontinuation of study treatment. 
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
 
 
 
  
 
  
 
 
 


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5.6 
Rule of exclusion criteria of analysis sets  
Table 5-18 
Subject Classification 
Analysis Set 
PD ID that 
    
cause subjects to be excluded 
Non-PD criteria that cause  
subjects to be excluded 
RAN 
INCL01* 
M-INCL05-randomized in error 
Not randomized 
FAS 
INCL01* 
Not in RAN; 
Mis-randomized subjects 
SAF 
INCL01* 
No study drug taken 
*Written informed consent must be obtained before any assessment is performed. 
 
5.7 
Descriptions of some efficacy endpoints 
5.7.1 
Investigator's Global Assessment grading (IGA) 
Table 5-19 
IGA 
IGA score 
Cutaneous Lichen 
Planus 
Mucosal Lichen 
Planus 
Lichen Planopilaris 
0 - Clear 
No disease. Possible 
flat, hyperpigmented 
lesions. 
No disease. 
No active disease. 
Hypopigmented, 
cicatricial patches. Pull 
test negative. 


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1 - Minimal 
Barely palpable (<0.5 
mm), scattered papules, 
mild erythema. 
Typically associated 
with minimal pruritus. 
Reticular, white, patch-
type striations involving 
any oral or genital 
mucosal site(s) 
(“Wickham Striae”). 
Absence of ulcers. 
Typically associated 
with no symptoms. 
Predominantly inactive 
disease (hypopigmented 
cicatricial patches). 
Absence of disease 
spreading. Pull test 
negative. Minimal scalp 
erythema and/or 
perifollicular erythema 
without scale. 
Typically associated 
with minimal pruritus. 
2 - Mild 
Moderately elevated 
papules (<1 mm) and/or 
small plaques (<2 cm2). 
Involvement of limited 
areas, erythema. 
Typically associated 
with mild pruritus. 
Plaque-type, mucosal 
lichen planus involving 
any oral or genital 
mucosal site(s). 
Absence of ulcers or 
presence of one focal 
ulceration (<0.5 cm2). 
Typically associated 
with mild pain or 
sensitivity. 
Rare perifollicular 
erythema, rare 
perifollicular 
hyperkeratosis and 
interfollicular scale. 
Stable or slowly 
spreading disease. Pull 
test negative. 
Typically associated 
with mild pruritus. 
3 - Moderate 
Thick, elevated (<2 
mm), hypertrophic, 
violaceous papules or 
presence of non-
hypertrophic, plaque-like 
disease (>2 cm2), either 
generalized or involving 
specific areas or specific 
locations (e.g. face, 
neck). Red/violaceous 
erythema, possible 
scales. 
Typically associated 
with moderate pruritus. 
Desquamative gingivitis 
or vulvitis. Presence of 
unilateral or bilateral 
ulcerations involving any 
oral or genital mucosal 
site(s). Overall area 
affected  by ulceration 
should be <2 cm2. 
Typically associated 
with moderate pain and 
sensitivity. 
Hairless patches with 
perifollicular and 
interfollicular erythema, 
follicular hyperkeratosis 
and interfollicular 
scaling. Active 
spreading disease. Pull 
test positive for telogen 
hairs. 
Typically associated 
with moderate pruritus, 
pain and/or burning. 
4 - Severe 
Generalized, papular or 
plaque-type,  elevated 
lesions (>2 mm) OR 
localized hypertrophic 
lesions (>2 cm2). 
Marked red/violaceous 
erythema. Possible 
scales, blisters and 
ulcers. 
Typically associated 
with severe pruritus. 
Presence of bilateral or 
extensive unilateral 
ulcers involving any oral 
or genital mucosal 
site(s). Overall area 
affected  by ulceration 
should be >2 cm2. 
Possible esophageal 
involvement 
(established by 
endoscopy). 
Typically associated 
with severe pain and 
sensitivity. 
Hairless patches with 
perifollicular and 
interfollicular, intense 
erythema, extensive 
perifollicular and 
interfollicular scaling. 
Crusting, pustules. 
Active spreading 
disease. Pull test 
positive for telogen or 
anagen hairs. 
Typically associated 
with severe pruritus, 
pain and/or burning. 
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or pruritus, may or may not be associated. 
5.7.2 
Patient Assessment of Itch (NRS) 
Itch is assessed with the following questions: 
• "Overall, how severe was your lichen planus-related itching during the past 24 hours?" 
• "How severe was your lichen planus-related itching at the worst moment during the past 
24 hours?" 
• "Overall, how bothered were you by your lichen planus-related itching during the past 24 
hours?" 
Answers are given on a numeric rating scale (NRS). The Patient Assessment of Itch will be 
assessed on all subjects. 
5.7.3 
Patient Assessment of Pain (NRS) 
Pain is assessed with the following questions: 
• "Overall, how severe was your lichen planus-related pain during the past 24 hours?" 
• "How severe was your lichen planus-related pain at the worst moment during the past 24 
hours?" 
• "Overall, how bothered were you by your lichen planus-related pain during the past 24 
hours?" 
Answers are given on a numeric rating scale (NRS). The Patient Assessment of Pain will be 
assessed on all subjects. 
5.7.4 
Physician´s assessment of surface area of disease (PSAD) 
Assessment scores range from 0-5, with lower scores corresponding to lower percentages of 
surface area with disease. 
0: clear 
1: <2% of the total body surface area. Small, localized papules 
2: 2-9% of the total body surface area. Lesions affecting limited areas (e.g. wrists or ankles) 
3: 10-29% of the total body surface area. Lesions affecting extensive areas (e.g. upper limbs or 
back) 
4: 30-50% of the total body surface area. Lesions affecting extensive areas or in multiple 
locations (e.g. trunk and lower/upper limbs) 
5: >50% of the total body surface area. Generalized involvement  
As reference, the percentages utilized for the Body Surface Area (BSA) assessment should be 
considered (head=10%, trunk=30%, upper limbs=20%, lower limbs=40%). 
Post-inflammatory hyperpigmentation should NOT be considered as surface area affected 
by the disease. 


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The PSAD assessment is required for all subjects enrolled in the CLP cohort. In addition, the 
PSAD assessment is required for subjects enrolled in the MLP cohort in case they have a 
concomitant cutaneous involvement. 
 
5.7.5 
Reticulations, erythema and ulcerations (REU) score 
The REU score is applied for all patients in the MLP cohort who have an oral presentation of 
the disease. In addition, the REU scoring is also done for patients in the CLP cohort in case they 
have a concomitant oral involvement. 
The assessment is done as follows: 
The oral cavity is divided into the following 10 sites: 
• upper/lower labial mucosa 
• right buccal mucosa 
• left buccal mucosa 
• dorsal tongue 
• ventral tongue 
• floor of mouth 
• hard palate mucosa 
• soft palate/tonsillar pillars 
• maxillary gingiva 
• mandibular gingiva 
The severity of the lesions is scored for each site individually according to the presence of 
reticular/hyperkeratotic, erosive/erythematous and ulcerative lesions: 
• Reticulation: reticular/hyperkeratotic lesions: 0 - 1  
• 0: no white striations 
• 1: presence of white striations or keratotic papules 
• Erythema: erosive/erythematous lesions by area of involvement: 0 - 3  
• 0: no lesion 
• 1: lesions < 1 cm2 
• 2: lesions 1 - 3 cm2 
• 3: lesions > 3 cm2 
• Ulceration: ulcerative lesions by area of involvement: 0-3  
• 0: no lesion 
• 1: lesions < 1 cm2 
• 2: lesions 1 - 3 cm2 
• 3: lesions > 3 cm2 
For each of the 3 clinical dimensions, a score is then derived by summation of the scores from 


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all 10 oral cavity sites: Reticular score = ∑R, erythema score = ∑E, and ulcerative score = ∑U. 
These 3 scores then add up to a total weighted score: ∑R + ∑(E x 1.5) + ∑(U x 2.0). 
 
5.7.6 
Lichen planopilaris Activity Index (LPPAI) 
The LPPAI assesses symptoms (pruritus, pain, burning), signs (erythema, perifollicular 
erythema and scale), a measure of activity (pull test) and extension of disease. These subjective 
and objective measures are assigned numeric values to establish a disease activity score. 
Whenever possible, the LPPAI assessment should be performed by the same evaluator 
throughout the study. It is applied for subjects in the LPP cohort only. 
Table 5-20 
LPPAI 
Symptoms  
Score 
Pruritus 
0 - 3 
Pain 
0 - 3 
Burning 
0 - 3 
Signs 
  
Scalp erythema 
0 - 3 
Perifollicular erythema 
0 - 3 
Perifollicular scale 
0 - 3 
Pull test 
0 / 1 & anagen / total 
Spreading 
0 - 2 
Score for signs and symptoms: 0=absent, 1=mild, 2=moderate, 3=severe 
Score for anagen pull test: To conduct the anagen pull test grasp a small group of 10 - 20 hairs 
between the thumb, second and third finger at the scalp end of the hair shafts and pull away 
from the scalp with a slow, firm perpendicular force to slide the fingers to the ends of the hair. 
The result is recorded both as a binary value (0 for no anagen hairs, 1 for the presence of anagen 
hairs) and as anagen hairs/total hairs pulled. 
Score for spreading: 0 = no spreading, 1 = indeterminate, 2 = spreading. When the hair loss is 
difficult to judge, the issue of spreading is recorded as indeterminate. 
The weights given to the symptoms (30%), signs (30%), anagen pull test (25%) and presence 
of spreading (15%) then lead to the final equation: 
LPPAI (0-10) = (pruritus + pain + burning + scalp erythema + perifollicular erythema + 
perifollicular scale)/3 + 2.5x(pull test) + 1.5x(spreading/2) 


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6 
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