 The number of investigators was updated to more accurately reflect the current number of investigators planned in this study.  The estimated date of last patient completed was updated based on the current estimated enrollment rate.  The proportion of patients in Cohort 1 and Cohort 2 have been adjusted to allow us to reinstate the original limit of ≤ 30% of patients who have received anti-TNF from RPC01-3101 protocol version 2.0, 2.1, 2.2, and 2.3. It is planned that the total sample size of the trial will remain unchanged.  The original limit of ≤ 30% of patients who have received anti-TNF from RPC01-3101 protocol version 2.0, 2.1, 2.2, and 2.3 has been reinstated for Cohort 1. A limit of ≤ 50% has been established for Cohort 2. These limits have been established based on ongoing development programs in UC that have confirmed that patients with anti-TNF experience achieve limited clinical response.  Study procedures have been clarified to allow for continuous enrollment of patients who have received anti-TNF therapy.

 A clarification was made to allow access to OCT images especially in case of suspicion of macular edema.  Clarification was made to allow sites with qualified personnel to perform the pulmonary function test onsite under the supervision of a pulmonologist.  A change was made to underscore that it is the choice of the patient to receive the VZV vaccination.  A correction was made for patients who test positive for HBs antigen. While patients who test positive for HBs antigen will still be excluded, the presence of the HBs antibody alone is the result of vaccination so these patients will be eligible for the trial.  A clarification was made in order to precisely define the timing of unblinding for Cohort 1 and the randomized component of the Maintenance Period.  A statement was added to clarify that treatment group assignment during the Maintenance Period for patients who received placebo in Cohort 1 will be unblinded to the Sponsor during the Maintenance Period.  Sections were added to clarify that analyses will be performed after the last patient has had their last visit in Cohort 1, Cohort 2 and the Maintenance Period, respectively.  The abbreviation list has been updated based on changes in this amendment

A clarification was made that Cohort 2 may need to be increased to ensure adequate powering of the Maintenance Period. The visit window for Visit Induction 3, Maintenance (M) 2, M 3, M 4, and M 5 was increased for operational efficiency. Added Safety Follow-Up section for consistency with other ongoing RPC1063 protocols. Revised instructions for elevated LFTs for consistency with other ongoing RPC1063 protocols. Added guidance for further liver function evaluation if a patient discontinues investigational drug due to elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5x ULN, or ALT or AST > 3x ULN and bilirubin > 2x ULN for additional clarification for the investigator. Changed “titration” to “dose escalation” throughout the protocol for consistency with other ongoing RPC1063 protocols. Added nomenclature and dose equivalency between RPC1063/ozanimod HCl (0.25 mg, 0.5 mg, and 1 mg) and ozanimod (0.23 mg, 0.46 mg, and 0.92 mg) for consistency across RPC1063 protocols. A change to the analysis method was made from the LOCF method to the NRI method Removed hemoglobin A1c from the chemistry panel because it is not needed for routine evaluation of patient safety. Minor editorial changes and changes for clarification were made.