­Amendment No. 1 was applicable in all countries. The main changes included: - Increase of the age of female patients of non-childbearing potential to 50 years old instead of 40 years old (inclusion criterion n°1) (except for female patients surgically sterile) as requested by USA IRB. - Addition of information regarding the management of an overdose of S201086/GLPG1972 as requested by Health Canada. - Addition of one withdrawal criterion “delta > 60 ms over baseline value (inclusion) with regards to ECG parameters as beside the absolute values on QTcF the delta is also an important parameter to evaluate for the safety of the patient. - Implementation of an evaluation of the consistency of the primary analysis’ results between Japanese patients and non-Japanese patients as recommended by the Pharmaceuticals and Medical Devices Agency (Japanese Competent Authorities). The initial randomisation list was stratified on 2 strata (Asia vs Rest of the World). In order to ensure balanced Japanese patients between treatment groups, the stratification factors of the randomisation list were modified accordingly (3 strata in the randomisation list: Japan vs South Korea/Taiwan vs Rest of the World). - Clarification of the choice of the target knee in inclusion criterion n°9.

Amendment No. 2 was applicable in all countries. It mainly concerned the widening of the recruitment: - Clarification and/or modification of inclusion criteria n°7, 9 and exclusion criteria n°24, 25, 27, 28, 29, 31, 32, 33, 38, 40, 44. - Update of forbidden/authorised concomitant treatments with regards to database reference.