PSARTROS II Observational Study Protocol Long term follow up of the Psoriasis-Arthritis & Bone Program (PSARTROS study) - Evaluation of inflammatory and structural joint damage in patients with psoriasis and psoriatic arthritis treated with secukinumab (PSARTROS II) Version 2.0 Date 08.05.2020 Study type Non-interventional Study (NIS) Study short title PSARTROS II Study code CAIN457F2301TE1 Indication Psoriasis Arthritis (PsA), Psoriasis (Pso) Planned study period 36 months Medicinal product(s) Secukinumab (Cosentyx) Investigator Initiator Universitätsklinikum Erlangen Medizinische Klinik 3 Ulmenweg 18 90154 Erlangen CONFIDENTIAL AND PROPRIETARY The contents of this document are confidential and proprietary to the institution. Unauthorized use, disclosure or reproduction is strictly prohibited. This document or parts thereof may not be disclosed to parties not associated with the clinical investigation without the prior written consent of the institution. CAIN457F2301TE1 Observational Study Protocol Page 1 von 36 v2.0, 08.05.2020 PSARTROS II LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS AE Adverse event ACR American College of Rheumatology ALT Alanine aminotransferase Anti CCP Anti-cyclic citrullinated peptide ANOVA Analysis of variance ALT Alanine aminotransferase AST Aspartate aminotransferase BP Blood pressure BSA Body surface area CASPAR Classification criteria for psoriatic arthritis CCP-AB Anti- cyclic citrullinated peptide CRP C-reactive protein / high sensitivity C-reactive protein DAPSA Disease Activity in Psoriatic Arthritis Score DAS Disease Activity Score DCF Data clarification form DCS Data Collection Sheet DLQI Dermatology Life Quality Index DMARD Disease Modifying Anti-Rheumatic Drug ESR Erythrocyte Sedimentation Rate EULAR European League Against Rheumatism µFEA Micro Finite element analysis GCP Good clinical practice GGT Gamma Glutamyl Transpeptidase GH Global Health HAQ-DI Health Assessment Questionnaire – Disability Index hsCRP high sensitivity C-reactive protein HR Heart rate HR-pQCT High-resolution peripheral quantitative computed tomography ICH International Conference on Harmonization IEC Independent ethics committee IL Interleukin LDH Lactate Dehydrogenase CAIN457F2301TE1 Observational Study Protocol Page 3 von 36 v2.0, 08.05.2020 PSARTROS II LEI Leeds Enthesitis Index Ln Natural logarithm IUD Intrauterine device MASES Maastricht Ankylosing Spondylitis Enthesitis Score MedDRA Medical Dictionary for Regulatory Activities MRI Magnetic resonance imaging µCT Micro-Computer tomomgraphy MSUS Musculoskeletal ultrasound MTX Methotrexate n Number of non-missing observations NSAID Non-steroidal anti-inflammatory drug OSP Observational Study Protocol PASI Psoriasis Area and Severity Index PsA Psoriatic Arthritis PsAiD Psoriatic Arthritis Impact of Disease (questionnaire) PsAMRIS Psoriatic Arthritis Magnetic Resonance Imaging Scoring System PsAQoL Psoriatic Arthritis Quality of Life Questionnaire Pso Psoriasis QoL Quality of Life PT Prothrombin time PTT Partial thromboplastin time RBC Red blood cell count RF Rheumatoid factor SAE Serious adverse event SAP Statistical analysis plan s.c. subcutaneously SD Standard deviation SEL Structural entheseal lesions SF 36 Medical Outcome Short Form (36) Health Survey SJC Swollen joint count SmPC Summary of product characteristics SOC System organ class SOP Standard operating procedure SPARCC Spondyloarthritis Consortium of Canada Score sqrt Square root TJC Tender joint count CAIN457F2301TE1 Observational Study Protocol Page 4 von 36 v2.0, 08.05.2020 PSARTROS II TNF Tumor necrosis factor VAS Visual analogue scale vBMD volumetric bone mineral density WBC White blood cell count CAIN457F2301TE1 Observational Study Protocol Page 5 von 36 v2.0, 08.05.2020 PSARTROS II Table of Contents SIGNATURE PAGE ......................................................................................................................... 2 List of Abbreviations and Definitions of Terms .......................................................................... 3 1 STUDY ADMINISTRATIVE STRUCTURE ............................................................................ 10 1.1 Responsibilities ................................................................................................................. 10 2 INTRODUCTION .................................................................................................................... 11 2.1 Study background ............................................................................................................. 11 2.2 Study rationale .................................................................................................................. 11 2.3 Benefit-risk assessment .................................................................................................... 12 3 STUDY OBJECTIVES............................................................................................................ 12 3.1 Primary objective ............................................................................................................... 12 3.2 Secondary objectives ........................................................................................................ 12 4 STUDY DESIGN ..................................................................................................................... 12 4.1 Type of Study .................................................................................................................... 12 4.1.1 Study site .................................................................................................................... 13 4.1.2 Time schedule ............................................................................................................ 13 4.1.3 Duration of observation per patient ............................................................................ 13 5 STUDY POPULATION ........................................................................................................... 13 5.1 Selection of study population ............................................................................................ 13 5.2 Inclusion criteria ................................................................................................................ 13 5.3 Exclusion criteria ............................................................................................................... 14 5.4 Removal of patients from assessment .............................................................................. 15 5.4.1 Discontinuation of patients.......................................................................................... 15 5.4.2 Premature termination or suspension of the study ..................................................... 15 6 TREATMENT ......................................................................................................................... 15 6.1 Drug treatment .................................................................................................................. 15 6.2 Previous and concomitant therapies ................................................................................. 16 7 Description of evaluation instruments/ parameters ......................................................... 16 7.1 Clinical Assessments ........................................................................................................ 16 7.1.1 Medical History ........................................................................................................... 16 7.1.2 Physical Examination .................................................................................................. 16 7.1.3 Disease activity ........................................................................................................... 17 7.1.4 Clinical evaluation by means of patients’ self-assessment ........................................ 19 7.1.5 Imaging diagnostics .................................................................................................... 21 7.2 Laboratory evaluations ...................................................................................................... 22 7.2.1 Biomarkers .................................................................................................................. 22 7.2.2 Tissue analysis ........................................................................................................... 23 7.3 Overview of study activities ............................................................................................... 23 8 Methods ................................................................................................................................. 24 8.1 Data collection for evaluation ............................................................................................ 24 8.2 Statistical Analysis ............................................................................................................. 25 8.2.1 Sample size ................................................................................................................ 25 8.2.2 Analysis sets ............................................................................................................... 25 8.2.3 Variables for analysis .................................................................................................. 25 8.2.4 Statistical analysis methods........................................................................................ 26 CAIN457F2301TE1 Observational Study