A Phase 2, Multi-Center, Open-Label Induction Trial With Extension Period to Access Endoscopic Improvement and Changes in Intestinal and Serum Biomarkers in Patients With Moderately to Severely Active Crohn's Disease Receiving Oral RPC1063 as Induction Therapy
Phase: PHASE2
Conditions: Crohn's Disease
Sponsor: Celgene

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
1 
1. 
CLINICAL TRIAL PROTOCOL 
Protocol Title:  
A Phase 2, Multi-Center, Open-Label Induction Trial with 
Extension Period to Assess Endoscopic Improvement and 
Changes in Intestinal and Serum Biomarkers in Patients 
with Moderately to Severely Active Crohn's Disease 
Receiving Oral RPC1063 as Induction Therapy 
Protocol Number: 
RPC01-2201 
Version and Date: 
 
 
5.0 dated 24 May 2019 
Replaces Version: 
 
 
4.0 dated 29 May 2018 
Investigational Product: 
RPC1063 
IND No.: 
126,740 
EudraCT No.: 
2015-002025-19 
Trial Phase: 
2 
Sponsor: 
  
 
 
 
 
Sponsor Medical Monitor: 
W. Jerry Liu, MD 
  
 
 
 
 
CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional 
review board. The information contained in this document is regarded as 
confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by 
law or regulations. Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them. 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
2 
SIGNATURES 
PROTOCOL TITLE:  A Phase 2, Multi-Center, Open-Label Induction Trial with Extension 
Period to Assess Endoscopic Improvement and Changes in Intestinal and Serum Biomarkers in 
Patients with Moderately to Severely Active Crohn's Disease Receiving Oral RPC1063 as 
Induction Therapy  
PROTOCOL NO:  RPC01-2201 
 
 
{See appended electronic signature page} 
 
 
Signature 
 
Date 
 
 
 
 
 
 
 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
3 
Sponsor:  Celgene International II Sàrl 
 
 
 
 
 
 
 
 
 
Signature of Celgene International II Sàrl 
Representative 
 
Date  
 
 
 
 
 
 
 
 
Printed Name of Celgene International II Sàrl Representative 
 
 
 
 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
4 
2. 
SYNOPSIS 
Sponsor/Company: Celgene International II Sàrl  
Investigational Product: RPC1063 
Name of Active Ingredient: RPC1063 
Trial Title: 
A Phase 2, Multi-Center, Open-Label Induction Trial with Extension Period to Assess 
Endoscopic Improvement and Changes in Intestinal and Serum Biomarkers in Patients 
with Moderately to Severely Active Crohn's Disease Receiving Oral RPC1063 as 
Induction Therapy 
Brief Title: 
Open-Label  Endoscopic Improvement Trial of RPC1063 for Moderate to Severe 
Crohn’s Disease 
Protocol No: 
RPC01-2201 
Investigators: 
Approximately 60-80 
Regions: 
North America, Europe 
Trial Duration:  3 years  
Phase:  2 
Objectives: 
Induction Period 
Primary: 
 
To assess endoscopic improvement following treatment with RPC1063  
Secondary: 
 
To characterize clinical improvement, response, and remission following treatment with RPC1063  
 
To assess changes in intestinal and blood biomarkers following treatment with RPC1063 by 
characterizing the following: 
 
Intestinal mucosa histopathologic disease activity 
 
Select cellular, protein, and molecular biomarkers in the intestinal mucosa and blood 
 
To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of RPC1063 
 
To assess the safety of RPC1063  
Extension Period 
Primary: 
 
To characterize the longer term safety of continued dosing of RPC1063 
Secondary: 
 
To characterize endoscopic improvement at Week 52 
 
To characterize the histopathological changes of the intestinal mucosa at Week 52 
 
To characterize the effect of RPC1063 in maintaining clinical improvement over time 
Methodology:  
This is an open label trial comprised of 2 periods – a 12 week Induction Period and an Extension Period 
(148 weeks).  Eligible patients will enter into the trial through the Induction Period and those who complete 
the Induction Period will have the opportunity to enter into the Extension Period.  
Induction Period: 
Patient eligibility will be determined during a 5-week Screening Period prior to first dose of investigational 
drug.  All eligible patients will complete a 7-day dose escalation regimen consisting of 4 days of treatment 
with RPC1063/ozanimod HCl 0.25 mg (equivalent to ozanimod 0.23 mg) daily followed by 3 days of 
treatment with RPC1063/ozanimod HCl 0.5 mg (equivalent to ozanimod 0.46 mg) daily, with the final 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
5 
RPC1063/ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) daily dose to be reached on Day 8.  Patients 
will then continue on open label at RPC1063 1 mg/day during the Induction Period for 11 weeks.  At Week 
12 patients will be evaluated for endoscopic and clinical response/remission. 
Patients who complete the Induction Period will have the opportunity to receive continued treatment with 
RPC1063 in the Extension Period.  Investigators should assess patient’s clinical status at the end of the 
Induction Period and, using clinical judgment, determine if the patient should continue into the Extension 
Period or withdraw from the trial and receive alternative therapy. 
Extension Period: 
All patients will receive RPC1063 1 mg daily dose in the Extension Period and may receive treatment 
through Week 160.  During the Extension Period, the investigator should continue to assess the patient’s 
clinical status and based on clinical judgment determine if the patient should continue or withdraw from the 
trial and receive alternative therapy. 
Patients who complete the Week 160 visit may have the option to immediately enter (without completing the 
30-day and 90-day Safety Follow-up Visits) the open-label extension Phase 3 Crohn’s disease Study 
. 
Diagnosis and main criteria for inclusion:  
Inclusion Criteria: 
1. Male or female patients aged 18 to 75 years, inclusive  
2. Diagnosis of Crohn’s disease for at least 2 months (prior to Screening) by clinical endoscopic evidence 
and corroborated by a histology report (Note: histopathology may be performed during Screening if no 
prior report is readily available) 
3. Crohn’s disease Activity Index score of 220 to 450 inclusive with an SES-CD score of ≥ 6.  (If disease 
isolated to ileum, the requirement will be a SES-CD score ≥ 4) 
4. Average daily stool score ≥ 4 points and/or an average daily abdominal pain score of ≥ 2 points 
5. Patients must meet one of the following criteria: 
 
Have an inadequate response or loss of response to at least one of the following Crohn’s disease 
treatments: 
 
Aminosalicylates, oral aminosalicylates ≥2.4 g/day or ≥3 g/day sulfasalazine for at least 
4 weeks 
 
Corticosteroids, oral prednisone ≥ 30 mg or budesonide ≥ 9 mg for at least 2 weeks or an 
equivalent (to oral prednisone) of intravenous corticosteroid for 1 week 
 
Immunomodulators, oral azathioprine ≥ 1.5 mg/kg or 6-mercaptopurine 0.75 mg/kg 
(documentation of therapeutic level of 6-thioguanine is also acceptable) or methotrexate 
≥ 12.5 mg/week for at least 8 weeks 
 
Biologic therapy (TNFα antagonist or vedolizumab only) at an approved labeled dose used 
for induction therapy for at least 4 weeks or recurrence of disease activity despite 
scheduled maintenance therapy.  (Biologic therapy exposed patients will be capped at 50% 
of total enrolled patients) 
 
And/or have been intolerant to any of the above mentioned therapies (e.g., unable to achieve 
doses, dose levels, or treatment durations because of treatment related side effects and/or 
laboratory abnormalities) 
6. The following background therapies for Crohn’s disease will be permitted on a stable dose: 
 
Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide) at a stable dose 
for at least 3 weeks prior to Screening endoscopy 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
6 
 
Prednisone (doses ≤ 20 mg per day) or equivalent at a stable dose for at least 2 weeks prior to 
Screening endoscopy 
 
Budesonide therapy at a stable dose (dose ≤ 9 mg per day) for at least 2 weeks prior to 
Screening endoscopy 
 
Antibiotics used for the treatment of Crohn’s disease (i.e., ciprofloxacin, metronidazole) at a 
stable dose for at least 2 weeks prior to Screening endoscopy 
7. If oral aminosalicylates or corticosteroids have been recently discontinued, they must have been 
stopped for at least 2 weeks prior to the endoscopy used for baseline endoscopy score 
8. Female patients of childbearing potential: 
Must agree to practice a highly effective method of contraception throughout the trial until completion 
of the 90-day Safety Follow-up Visit. Highly effective methods of contraception are those that alone or 
in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently 
and correctly. Acceptable methods of birth control in the trial are the following: 
 
combined hormonal (oestrogen and progestogen containing) contraception, which may be oral, 
intravaginal, or transdermal  
 
progestogen-only hormonal contraception associated with inhibition of ovulation, which may 
be oral, injectable, or implantable 
 
placement of an intrauterine device (IUD) 
 
placement of an intrauterine hormone-releasing system (IUS) 
 
bilateral tubal occlusion 
 
vasectomised partner 
 
complete sexual abstinence  
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of 
contraception. Female condom and male condom should not be used together. 
Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted for 
female subjects of childbearing potential. The Investigator will educate all FCBP about the different 
options of contraceptive methods or abstinence as appropriate. The subject will be re-educated every 
time her contraceptive measures/methods or ability to become pregnant changes. The female subject’s 
chosen form of contraception must be effective by the time the female subject is randomized into the 
study (for example, hormonal contraception should be initiated at least 28 days before randomization). 
9. Ability to provide written informed consent and to be compliant with the schedule of protocol 
assessments 
10. Must have documentation of positive Varicella zoster virus (VZV) immunoglobulin G (IgG) antibody 
status or complete VZV vaccination at least 30 days prior to first dose of investigational drug 
11. For patients at high risk (i.e., family history, disease duration) for colonic malignancy, documented 
evidence of having had a surveillance colonoscopy within the last 2 years or according to local medical 
guidelines to evaluate for polyps, dysplasia, or malignancy.  If no recent history of surveillance 
colonoscopy, this can be done as part of colonoscopy performed during Screening 
Diagnosis and Main Criteria for Exclusion: 
Exclusions Related to General Health: 
1. 
Diagnosis of ulcerative colitis or indeterminate colitis 
2. 
Crohn’s disease isolated to the stomach, duodenum, jejunum, or peri-anal region, without colonic or 
ileal involvement 
3. 
Known strictures or stenosis leading to symptoms of obstruction 
4. 
Current stoma or need for ileostomy or colostomy 
5. 
Extensive small bowel resection (>100 cm) or known diagnosis of short bowel syndrome 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
7 
6. 
Suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated 
7. 
Currently require or are anticipated to require surgical intervention for Crohn’s disease during the 
Induction Period 
8. 
Currently receiving total parenteral nutrition 
9. 
Positive stool culture for pathogens (ova and parasites, bacteria) or positive test for Clostridium 
difficile (C. difficile) at Screening.  Patients may be treated and retested but must have negative stool 
culture for pathogens (ova and parasites, bacteria) within 30 days prior to first dose of investigational 
drug and 60 days prior to first dose of investigational drug for C. difficile 
10. Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG) measured during 
Screening  
11. Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric or other 
major systemic disease making implementation of the protocol or interpretation of the trial difficult or 
that would put the patient at risk by participating in the trial 
12. Clinically relevant cardiovascular conditions, including history or presence of: 
 
Recent (within the last 6 months) occurrence of myocardial infarction, unstable angina, stroke, 
transient ischemic attack, decompensated heart failure requiring hospitalization, Class III/IV 
heart failure, sick sinus syndrome, or severe untreated sleep apnea 
 
Prolonged QTcF interval (QTcF > 450 msec males, > 470 msec females), or at additional risk 
for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital long-QT syndrome) 
 
Resting HR < 55 beats per minute (bpm) when taking vitals as part of a physical examination at 
Screening 
 
Mobitz type 2nd degree or 3rd degree AV block 
13. History of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with hemoglobin 
A1c > 9%, or diabetic patients with significant co-morbid conditions such as retinopathy or 
nephropathy 
14. History of uveitis or known macular edema 
15. Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including 
tuberculosis [TB] or atypical mycobacterial disease [but excluding fungal infection of nail beds, minor 
upper respiratory tract infections and minor skin infections]) or any major episode of infection that 
required hospitalization or treatment with intravenous antibiotics within 30 days of Screening or oral 
antibiotics within 14 days of Screening.   
16. History or known presence of recurrent or chronic infection (e.g., hepatitis A, B, or C, human 
immunodeficiency virus (HIV); recurrent urinary tract infections are permitted. 
17. History of cancer, including solid tumors and hematological malignancies (except basal cell and in situ 
squamous cell carcinomas of the skin that have been excised and resolved) 
18. Past or current evidence of colonic dysplasia 
19. History of alcohol or drug abuse within 1 year prior to first dose of investigational drug 
20. History of or currently active primary or secondary immunodeficiency 
Exclusions Related to Medications: 
21. History of treatment with a biologic agent within 5 elimination half-lives of that agent prior to first 
dose of investigational drug 
22. History of treatment with an investigational agent within 5 elimination half-lives of that agent prior to 
first dose of investigational drug 
23. History of treatment with topical rectal 5-ASA or steroids within 2 weeks of Screening  
24. History of primary non-response to two approved biologic therapies used for the treatment of Crohn’s 
disease 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
8 
25. Receipt of a live vaccine or live attenuated vaccine within 4 weeks prior to Screening 
26. Previous treatment with lymphocyte-depleting therapies (e.g., Campath, anti-CD4, cladribine, 
rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow 
transplantation, alemtuzumab, daclizumab) 
27. Treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16 weeks of 
Screening 
28. Previous treatment with D-penicillamine, leflunomide, or thalidomide  
29. Previous treatment with natalizumab or fingolimod 
30. History of treatment with intravenous immune globulin (IVIg), plasmapheresis, within 3 months prior 
to first dose of investigational drug 
31. Planned concurrent treatment with immunosuppressive agents (e.g., azathioprine, 6-MP, or 
methotrexate) after enrollment.  Patients receiving azathioprine, 6-MP or methotrexate at Screening 
must discontinue treatment with these agents prior to first dose of investigational drug. 
32. Chronic non-steroidal anti-inflammatory drug (NSAID) use (Note: occasional use of NSAIDs and 
acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day 
is permitted) 
33. Treatment with Class Ia or Class III anti-arrhythmic drugs, or treatment with two or more agents in 
combination known to prolong PR interval 
34. Treatment with any of the following drugs or interventions within the corresponding timeframe: 
 
At Day 1  
 
 
CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin) 
 
Two weeks prior to Day 1 
 
Monoamine oxidase inhibitors (eg, selegiline, phenelzine) 
Exclusions Related to Laboratory Results: 
35. Serum creatinine  1.4 mg/dL for women or  1.6 mg/dL for men 
36. Liver function impairment or persisting elevations of aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT)  2 times the upper limit of normal (ULN), or direct bilirubin  1.5 times the 
ULN 
37. Platelet count  100,000/μL 
38. Hgb  8.5 g/dL 
39. Neutrophils < 1500/μL 
40. Absolute WBC count < 3500/μL 
41. Absolute lymphocyte count < 800/μL 
42. Electrocardiogram (ECG) showing any clinically significant abnormality (e.g., acute ischemia, any 
significant heart conduction abnormality [e.g., left bundle branch block]) 
43. Forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC) < 70% of predicted 
values at Screening 
Test Product, Dose, and Mode of Administration: 
Induction Period: 
All patients will receive RPC1063/ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) capsule orally 
starting with a 7-day dose escalation regimen of RPC1063/ozanimod HCl 0.25 mg (equivalent to ozanimod 
0.23 mg) daily on Days 1 through 4 and RPC1063/ozanimod HCl 0.5 mg (equivalent to ozanimod 0.46 mg) 
daily (administered as two RPC1063/ozanimod HCl 0.25 mg [equivalent to ozanimod 0.23 mg] capsules) on 
Days 5 through 7, continuing with RPC1063/ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) daily 
through Week 12. 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
9 
Extension Period: 
All patients will receive RPC1063/ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) capsule orally 
once daily through Week 160. 
Reference therapy, dosage and mode of administration: Not applicable 
Duration of treatment:  
Induction Period: 12 weeks  
Extension Period: 148 weeks 
Endpoints: 
Definitions  
Endoscopic 
Response: SES-CD decrease from baseline of ≥ 50% 
Remission: SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points with no SES-CD sub-score > 1 point  
CDAI 
Clinical Response: CDAI reduction from baseline of ≥ 100 points 
Clinical Remission: CDAI score of < 150 
PRO2  
Clinical Response:  PRO2 decrease ≥ 50% 
Clinical Remission:  Average daily stool score ≤ 3 points AND average daily abdominal pain score ≤ 1 point 
Mucosal Healing   
Endoscopic remission plus histologic improvement 
Induction Period 
Primary Efficacy Endpoint:  
 
Change in SES-CD from baseline at Week 12 
Other Efficacy Endpoints: 
 
Change in CDAI score from baseline at Week 12 
 
Proportion of patients with clinical remission based on CDAI at Week 12  
 
Proportion of patients with clinical response based on CDAI at Week 12 
 
Proportion of patients with clinical remission based on PRO2 definitions at Week 12 
 
Proportion of patients with clinical response based on PRO2 definitions at Week 12 
 
Proportion of patients with endoscopic remission based on SES-CD definitions at Week 12 
 
Proportion of patients with endoscopic response based on SES-CD definitions at Week 12 
 
Change in intestinal mucosa histopathologic features and disease activity 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Improvement in perianal and enterocutaneous fistulas at Week 12 in those patients with fistulas at 
baseline 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
10 
Extension Period 
Efficacy Endpoints: 
 
Proportion of patients in endoscopic remission based on SES-CD definitions at Week 52 
 
Proportion of patients in endoscopic response based on SES-CD definitions at Week 52 
 
Proportion of patients in clinical remission based on CDAI at Week 52  
 
Proportion of patients in clinical response based on CDAI at Week 52  
 
Proportion of patients in clinical remission based on PRO2 definitions at Week 52 
 
Proportion of patients in clinical response based on PRO2 definitions at Week 52 
 
Proportion of patients in clinical remission at Week 52 based on CDAI and PRO2 definitions who 
are off corticosteroids of those on corticosteroids at baseline  
 
Proportion of patients in clinical remission based on CDAI over time  
 
Proportion of patients in clinical response based on CDAI over time  
 
Proportion of patients in clinical remission based on PRO2 definitions over time 
 
Proportion of patients in clinical response based on PRO2 definitions over time  
 
Change in intestinal mucosa histopathologic features, histologic disease activity, and biomarkers 
over time 
 
Change in fecal calprotectin and serum C-reactive protein (CRP) levels over time 
 
Improvement in perianal and enterocutaneous fistulas in those patients with fistulas at baseline over 
time 
Pharmacokinetic and Pharmacodynamic Endpoints 
 
Plasma concentration of RPC1063 and active metabolites at scheduled assessments during the 
treatment period  
 
Absolute lymphocyte count (ALC) derived from hematology laboratory results 
 
Peripheral immune cell phenotype determined by Flow cytometry  
Safety:  
The incidence, severity, relationship and type of treatment-emergent adverse events (TEAEs), serious AEs 
(SAEs), AEs leading to discontinuation of investigational drug, and AEs of special interest, and clinically 
meaningful changes from baseline on clinical laboratory measures, vital signs, ECG, and physical 
examinations will be assessed. 
The safety of patients will be monitored by collection of treatment-emergent AEs, serious adverse events 
(SAEs), physical examinations, vital sign measurements, ECG results, optical coherence tomography (OCT), 
pulmonary function tests (PFTs), and clinical laboratory tests.  Patients who discontinue from treatment due 
to lack of response, AEs, or other reasons, even if alternative treatment is given, will complete an Early 
Termination Visit and will be followed for 90 days for collection of safety data and for the assessment of 
their disease status. 
Statistical Methods: 
Induction and Extension Period Efficacy 
This is an open-label, single-arm trial.  As such, there are no hypothesis tests on the data collected in this 
trial.  In general, descriptive summaries will be presented for the efficacy and safety variables collected.  
Continuous variables will be summarized using number of patients (n), mean, standard deviation (SD), 
median, minimum, and maximum.  Categorical variables will be summarized using frequency counts and 
percentages. 
Safety  
All treatment-emergent AEs will be coded and tabulated by system organ class and preferred term.  Adverse 
events will be monitored during the trial and the data analyzed with respect to incidence as well as severity 
and potential relationship of the AEs to investigational drug.  The incidence of AEs, SAEs, AEs of special 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
11 
interest, and AEs leading to discontinuation will be summarized and presented in descending order of 
frequency.  Associated laboratory parameters such as hepatic enzymes, renal function, and hematology 
values will be grouped and presented together.  Individual patient values will be listed and values outside of 
the standard reference range will be flagged.  Shift tables and analyses of changes from baseline will be 
produced.  The change from baseline for each of the vital signs and ECG parameters will be summarized.  
The incidence of abnormal vital signs parameters and outlier ECG results will be tabulated. 
Sample Size Justification 
The sample size of 60 patients has been chosen to enable estimates of response and remission rates with 
reasonable precision.  Assuming a remission rate of 15% and a response rate of 30%, it is estimated that the 
confidence interval (half-widths of the 95% CI) around the proportion of patients in response and remission 
will be 12.8% and 16.4% for 30 patients and 9.0% and 11.6% for 60 patients. 
Version and Date:  5.0 dated 24 May 2019 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
12 
3. 
TABLE OF CONTENTS 
1. 
CLINICAL TRIAL PROTOCOL .................................................................................1 
SIGNATURES .................................................................................................................................2 
 
 
3. 
TABLE OF CONTENTS ...........................................................................................12 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................17 
5. 
INTRODUCTION ......................................................................................................20 
5.1. 
Crohn’s Disease ..........................................................................................................20 
5.2. 
RPC1063 .....................................................................................................................20 
 
 
 
 
6. 
TRIAL OBJECTIVES AND ENDPOINTS ...............................................................23 
6.1. 
Trial Objectives ..........................................................................................................23 
6.1.1. 
Induction Period Primary Objective ...........................................................................23 
6.1.2. 
Induction Period Secondary Objectives ......................................................................23 
6.1.3. 
Extension Period Primary Objective ..........................................................................23 
6.1.4. 
Extension Period Secondary Objectives .....................................................................23 
6.2. 
Endpoints ....................................................................................................................23 
6.2.1. 
Induction Period Endpoints ........................................................................................23 
6.2.2. 
Extension Period Efficacy Endpoints .........................................................................24 
6.2.3. 
Safety Endpoints .........................................................................................................25 
6.2.4. 
Pharmacokinetic and Pharmacodynamic Endpoints ...................................................25 
7. 
INVESTIGATIONAL PLAN .....................................................................................26 
7.1. 
Overall Trial Design ...................................................................................................26 
7.1.1. 
Induction Period ..........................................................................................................26 
7.1.2. 
Extension Period .........................................................................................................26 
7.2. 
Criteria for Trial Termination .....................................................................................27 
7.3. 
Schedule of Events .....................................................................................................27 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................35 
8.1. 
Patient Inclusion Criteria ............................................................................................35 
8.2. 
Patient Exclusion Criteria ...........................................................................................37 
8.3. 
Trial Discontinuation ..................................................................................................39 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
13 
9. 
TRIAL TREATMENTS .............................................................................................42 
9.1. 
Treatments Administered ............................................................................................42 
9.1.1. 
Instructions for Missed Dose(s) of RPC1063 Capsules .............................................42 
9.1.2. 
Induction Period ..........................................................................................................42 
9.1.3. 
Extension Period .........................................................................................................42 
9.2. 
Selection of Dose in the Trial .....................................................................................42 
9.3. 
Method of Assigning Patients to Treatment Groups ..................................................43 
9.4. 
Selection and Timing of Dose for Each Patient ..........................................................43 
9.5. 
Prior and Concomitant Treatments .............................................................................43 
9.5.1. 
Steroid Taper ..............................................................................................................43 
9.5.2. 
Allowed Medications ..................................................................................................44 
9.5.3. 
Concomitant Medications Prohibited Through the 30-Day Safety Follow-up 
Visit .............................................................................................................................44 
9.5.4. 
Concomitant Medications Between the 30-Day Safety Follow-up Visit and 
the 90-Day Safety Follow-up Visit .............................................................................45 
9.6. 
Medical Care of Patients after End of Trial ................................................................45 
9.7. 
Treatment Compliance ................................................................................................45 
9.8. 
Blinding ......................................................................................................................46 
10. 
INVESTIGATIONAL DRUG MATERIALS AND MANAGEMENT ....................47 
10.1. 
Investigational Drug ...................................................................................................47 
10.2. 
Packaging and Labeling ..............................................................................................47 
10.3. 
Investigational Drug Accountability ...........................................................................47 
11. 
ASSESSMENT OF EFFICACY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS ........................................................................................48 
11.1. 
Efficacy Assessments .................................................................................................48 
11.1.1. 
Primary Efficacy Assessments ...................................................................................48 
11.1.2. 
SES-CD.......................................................................................................................48 
11.1.3. 
Crohn’s Disease Activity Index ..................................................................................48 
11.1.4. 
PRO2...........................................................................................................................50 
11.1.5. 
Un-weighted Stool Frequency and Abdominal Pain ..................................................50 
11.1.6. 
Other Efficacy Measures ............................................................................................50 
11.1.6.1. 
Enterocutaneous and Perianal Fistula Drainage Assessment .....................................50 
11.1.7. 
Efficacy Definitions ....................................................................................................50 

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11.2. 
Pharmacokinetics and Pharmacodynamics .................................................................51 
11.2.1. 
Pharmacokinetics and Pharmacodynamics .................................................................51 
11.2.2. 
Flow Cytometry ..........................................................................................................51 
12. 
ASSESSMENT OF SAFETY .....................................................................................52 
12.1. 
Safety Parameters .......................................................................................................52 
12.1.1. 
Physical Examination .................................................................................................52 
12.1.2. 
Vital Signs ..................................................................................................................52 
12.1.3. 
Electrocardiogram .......................................................................................................52 
12.1.4. 
Ophthalmological Examination ..................................................................................53 
12.1.5. 
Pulmonary Function Tests ..........................................................................................53 
12.1.6. 
Height and Weight ......................................................................................................53 
12.1.7. 
Monitoring of Adverse Events and Serious Adverse Events ......................................53 
12.1.8. 
Monitoring of Concomitant Therapy ..........................................................................53 
12.1.9. 
Guidelines for Monitoring Patients Taking Their First Dose of RPC1063 ................53 
12.1.10. 
Clinical Laboratory Evaluations .................................................................................54 
12.2. 
Adverse and Serious Adverse Events .........................................................................56 
12.2.1. 
Definition of Adverse Events .....................................................................................56 
12.2.2. 
Definition of Serious Adverse Events ........................................................................56 
12.2.3. 
Assessment of Adverse Event Severity ......................................................................57 
12.2.4. 
Assessment of Adverse Event Relationship to Investigational Drug .........................57 
12.2.5. 
Reporting of Serious Adverse Events .........................................................................58 
12.2.6. 
Reporting of Serious Adverse Events to Regulatory Authorities and 
Investigators ................................................................................................................59 
12.2.7. 
Adverse Events of Special Interest .............................................................................59 
12.2.8. 
Monitoring of Patients with Adverse Events, Serious Adverse Events, and 
Adverse Events of Special Interest .............................................................................62 
12.2.9. 
Data Safety Monitoring Board ....................................................................................62 
12.2.10. 
Treatment of Overdose of Investigational Drug .........................................................62 
12.2.11. 
Procedures in Case of Pregnancy ...............................................................................62 
 
 
13. 
PLANNED STATISTICAL METHODS ...................................................................64 
13.1. 
Determination of Sample Size ....................................................................................64 
13.2. 
Statistical Methods ......................................................................................................64 

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13.2.1. 
General Considerations ...............................................................................................64 
13.2.2. 
Analysis Populations ..................................................................................................64 
13.3. 
Disposition, Demographics and Baseline Characteristics ..........................................64 
13.4. 
Induction and Extension Efficacy ...............................................................................65 
13.5. 
Safety Analyses ..........................................................................................................65 
13.6. 
Pharmacokinetic Analyses ..........................................................................................65 
13.7. 
Interim Analyses .........................................................................................................65 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................66 
14.1. 
Monitoring ..................................................................................................................66 
14.2. 
Data Management/Coding ..........................................................................................66 
14.3. 
Quality Assurance and Inspections .............................................................................67 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................68 
15.1. 
Study Monitor and Source Data Verification .............................................................68 
15.2. 
Product Quality Complaint .........................................................................................68 
16. 
ETHICS ......................................................................................................................70 
16.1. 
Institutional Review Board or Independent Ethics Committee ..................................70 
16.2. 
Ethical Conduct of the Trial .......................................................................................70 
16.3. 
Patient Information and Consent ................................................................................70 
16.4. 
Patient Data Protection ...............................................................................................71 
16.5. 
Investigator Obligations ..............................................................................................71 
16.6. 
Protocol Signatures .....................................................................................................71 
17. 
DATA HANDLING AND RECORD KEEPING ......................................................72 
17.1. 
Inspection of Records .................................................................................................72 
17.2. 
Retention of Records ..................................................................................................72 
18. 
PUBLICATION POLICY, FINANCING, AND INSURANCE ................................73 
 
 
20. 
APPENDIX: INVESTIGATOR SIGNATURE .........................................................75 
 

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LIST OF TABLES 
Table 1: 
Abbreviations ..............................................................................................................17 
Table 2: 
Schedule of Events for Induction Period ....................................................................28 
Table 3: 
Schedule of Events for Extension Period ...................................................................31 
Table 4: 
Examples of Prohibited Cardiac Medications (Systemic Use) ...................................45 
Table 5: 
Definitions of Simple Endoscopic Score for Crohn's Disease ...................................48 
Table 6: 
CDAI Assessment .......................................................................................................49 
Table 7: 
Crohn's Disease Severity Definitions .........................................................................50 
Table 8: 
PRO 2 Assessment ......................................................................................................50 
 

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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this protocol. 
Table 1: 
Abbreviations 
Abbreviation or Specialist Term 
Definition 
5-ASA 
5-Aminosalicylic acid 
6-MP 
6-Mercaptopurine 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALC 
Absolute lymphocyte count 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
Anti-TNF 
Anti-tumor necrosis factor 
AST 
Aspartate aminotransferase 
AV 
Atrioventricular 
AZA 
Azathioprine 
BCRP 
Breast Cancer Resistance Protein 
CD 
Crohn’s disease 
CDAI 
Crohn’s Disease Activity Index 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
DDI 
Drug drug interaction 
DLCO 
Diffusion capacity of the lung for carbon 
monoxide 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
Early Term 
Early termination 
FEV1 
Forced expiratory volume at 1 second 
FVC 
Forced vital capacity 
GCP 
Good Clinical Practice 

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Abbreviation or Specialist Term 
Definition 
HBsAg 
Hepatitis B surface antigen 
hCG 
human chorionic gonadotropin 
HCV 
Hepatitis C virus 
Hgb 
Hemoglobin 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
IBD 
Inflammatory bowel disease 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IFN 
Interferon 
IHC 
Immunohistochemistry 
IL 
Interleukin 
IRB 
Institutional Review Board 
ITT 
Intent to treat 
IUD 
Intrauterine device 
IUS 
Intrauterine-hormone releasing system 
IV 
Intravenous 
IVIg 
Intravenous immune globulin 
LAM 
Lactational amenorrhea method 
LFT 
Liver function test 
MMF 
Mycophenolate mofetil 
NASH 
Nonalcoholic steatohepatitis 
NSAID 
Nonsteroidal anti-inflammatory drug 
OCT 
Optical coherence tomography 
PD 
Pharmacodynamic 
PE 
Physical examination 
PFT 
Pulmonary function test (FEV1, FVC, and DLCO) 
PK 
Pharmacokinetic 
PQC 
Product Quality Complaint 
RT-PCR 
Reverse transcription polymerase chain reaction 
S1P1 
Sphingosine 1-phosphate 1 receptor 
SAE 
Serious adverse event 

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Abbreviation or Specialist Term 
Definition 
SD 
Standard deviation 
SES-CD 
Simple Endoscopic Score for Crohn’s Disease 
TB 
Tuberculosis 
TGFβ 
Transforming growth factor beta 
TNFα 
Tumor necrosis factor alpha 
UC 
Ulcerative colitis 
ULN 
Upper limit of normal 
VZV 
Varicella Zoster Virus 
WBC 
White blood cell 
WOCBP 
Women of child-bearing potential 

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6. 
TRIAL OBJECTIVES AND ENDPOINTS 
6.1. 
Trial Objectives 
6.1.1. 
Induction Period Primary Objective 
To assess endoscopic improvement following treatment with RPC1063 
6.1.2. 
Induction Period Secondary Objectives 
 To characterize clinical improvement, response, and remission following treatment 
with RPC1063  
 To assess changes in intestinal and blood biomarkers following treatment with 
RPC1063 by characterizing the following: 
 Intestinal mucosa histopathologic disease activity  
 Select cellular, protein, and molecular biomarkers in the intestinal mucosa and 
blood 
 To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of RPC1063  
 To assess the safety of RPC1063  
6.1.3. 
Extension Period Primary Objective 
To characterize the longer term safety of continued dosing of RPC1063  
6.1.4. 
Extension Period Secondary Objectives 
 To characterize endoscopic improvement at Week 52 
 To characterize the histopathological changes of the intestinal mucosa at Week 52 
 To characterize the effect of RPC1063 in maintaining clinical improvement over time 
6.2. 
Endpoints 
6.2.1. 
Induction Period Endpoints 
Patients in the Induction Period will be assessed for the following efficacy endpoints: 
Primary Efficacy Endpoint 
 Change in SES-CD score from baseline at Week 12. 
Other Efficacy Endpoints 
 Change in CDAI score from baseline at Week 12 
 Proportion of patients with clinical remission based on CDAI at Week 12 
 Proportion of patients with clinical response based on CDAI at Week 12 
 Proportion of patients with clinical remission based on PRO2 definitions at Week 12 

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 Proportion of patients with clinical response based on PRO2 definitions at Week 12 
 Proportion of patients with endoscopic remission based on SES-CD definitions at 
Week 12 
 Proportion of patients with endoscopic response based on SES-CD definitions at 
Week 12 
 Change in intestinal mucosa histopathologic features and disease activity 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 Improvement in perianal and enterocutaneous fistulas at Week 12 in those patients 
with fistulas at baseline 
6.2.2. 
Extension Period Efficacy Endpoints 
Patients in the Extension Period will be examined for the following efficacy endpoints: 
 Proportion of patients in endoscopic remission based on SES-CD definitions at Week 
52 
 Proportion of patients in endoscopic response based on SES-CD definitions at 
Week 52 
 Proportion of patients in clinical remission based on CDAI at Week 52 
 Proportion of patients in clinical response based on CDAI at Week 52 
 Proportion of patients in clinical remission based on PRO2 definitions at Week 52 
 Proportion of patients in clinical response based on PRO2 definitions at Week 52 
 Proportion of patients in clinical remission at Week 52 based on CDAI and PRO2 
definitions who are off corticosteroids of those on corticosteroids at baseline  
 Proportion of patients in clinical remission based on CDAI over time 
 Proportion of patients in clinical response based on CDAI over time 
 Proportion of patients in clinical remission based on PRO2 definitions over time 
 Proportion of patients in clinical response based on PRO2 definitions over time 

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 Change in intestinal mucosa histopathologic features, histologic disease activity, and 
biomarkers over time 
 Change in fecal calprotectin and serum C-reactive Protein levels over time 
 Improvement in perianal and enterocutaneous fistulas in those patients with fistulas at 
baseline over time 
6.2.3. 
Safety Endpoints 
The incidence, severity, relationship and type of TEAEs, SAEs, AEs leading to discontinuation 
of investigational drug, and AEs of special interest, and clinically meaningful changes from 
baseline on clinical laboratory measures, vital signs, electrocardiograms (ECGs), and physical 
examination will be assessed. 
Safety assessments will include the following: 
 Collection of AEs 
 Physical examinations 
 Vital sign measurements 
 ECG results 
 Optical coherence tomography 
 Pulmonary function tests (PFTs) (FEV1, FVC, and diffusion capacity of the lung for 
carbon monoxide [DLCO], where available) 
 Clinical laboratory tests 
6.2.4. 
Pharmacokinetic and Pharmacodynamic Endpoints 
Pharmacokinetic and PD endpoints will include the following: 
 
 
 
 
 
 
 

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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Trial Design 
This Phase 2, multi-center, open-label trial, to be conducted in North America and Europe, is 
designed to assess the endoscopic improvement, clinical response/remission, and changes in 
intestinal and blood biomarkers in patients with moderately to severely active Crohn’s disease 
receiving RPC1063 as induction therapy.  The trial comprises 2 periods: Induction (12 weeks) 
and Extension (148 weeks).  Patients will be entered into the trial through the Induction Period.  
A central reader will calculate the SES-CD for eligibility and assessment of the primary endpoint 
to ensure objectivity. 
The safety of patients will be monitored by collection of treatment-emergent AEs, serious 
adverse events (SAEs), physical examinations, vital sign measurements, ECG results, optical 
coherence tomography (OCT), pulmonary function tests (PFTs), and clinical laboratory tests. 
Patients who discontinue from treatment due to lack of response, AEs, or other reasons, even if 
alternative treatment is given, will complete an Early Termination Visit and will be followed for 
90 days for collection of safety data and for the assessment of their disease status. 
7.1.1. 
Induction Period 
The trial will enroll approximately 60 patients with moderately to severely active Crohn’s 
disease.  Patient eligibility will be determined during a 5-week Screening Period.  All patients 
who meet eligibility criteria and enter into the trial will complete a 7-day dose escalation 
regimen consisting of 4 days of treatment with RPC1063/ozanimod HCl 0.25 mg (equivalent to 
ozanimod 0.23 mg) daily followed by 3 days treatment with RPC1063/ozanimod HCl 0.5 mg 
(equivalent to ozanimod 0.46 mg) daily (administered as two 0.25 mg capsules), with the final 
dose level of RPC1063/ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) daily dose to be 
reached on Day 8.  Patients will then continue on RPC1063 1 mg daily during the Induction 
Period for 11 weeks. At Week 12 patients will be evaluated for endoscopic and clinical 
response/remission.   
Patients who complete the Induction Period will have the opportunity to receive continued 
treatment with RPC1063 in the Extension Period.  Investigators should assess patient’s clinical 
status at the end of the Induction Period and, using clinical judgment, determine if the patient 
should continue into the Extension Period or withdraw from the trial and receive alternative 
therapy. 
Induction Period visit schedule and procedures, including early termination and safety follow-up, 
are provided in Table 2.   
7.1.2. 
Extension Period 
All patients will receive RPC1063 1 mg daily dose in the Extension Period and may receive 
treatment through Week 160.   During the Extension Period, the investigator should continue to 
assess the patients clinical status and based on clinical judgment determine if the patient should 
continue or withdraw from the trial and receive alternative therapy.  Extension Period visit 
schedule and procedures, including early termination and safety follow-up, are provided in 
Table 3. 

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Patients who complete the Week 160 visit may have the option to immediately enter (without 
completing the 30-day or 90-day Safety Follow-up Visits) the open-label extension Phase 3 CD 
Study 
. 
7.2. 
Criteria for Trial Termination 
The Sponsor has the right to terminate the trial prematurely for safety reasons.  In addition, the 
Sponsor may terminate the trial prematurely for administrative reasons.  In all cases, all 
necessary measures must be taken to guarantee appropriate safety follow-up of all patients 
already included in the trial. 
The IEC or IRB and the Regulatory Authorities will be informed in writing about any premature 
termination of the trial. 
7.3. 
Schedule of Events 
The visit schedule and procedures for the Induction Period and Extension Period are provided in 
Table 2 and Table 3, respectively. 
 

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Table 2: 
Schedule of Events for Induction Period 
 
 
Trial Procedures 
Screening 
Induction Period 
 
Early Term 
Visit 
Safety Follow-up 
Dose Escalation 
1 mg Dose 
Visit I1 
Visit I2 
Visit I3 
Visit I4 
Day 1a,b 
Week 4b 
Week 8b 
Week 12b,c 
Day-35 
to 0 
Day 1 
Day 28±3 
Day 56±3 
Day 84±3 
Last Dose 
+30 ±3 days 
Last Dose 
+90 
±10 daysr 
 
Informed consent 
X 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical historyd,e 
X 
X 
 
 
 
 
 
 
Viral serologyf 
X 
 
 
 
 
 
 
 
Stool cultureg 
X 
 
 
 
 
 
 
 
Dispense investigational 
drug 
 
X 
X 
X 
X 
 
 
 
Administer 
investigational drug at 
clinic 
 
X 
X 
X 
X 
 
 
 
Review drug compliance 
 
 
X 
X 
X 
X 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
Medical procedures 
(non-trial) 
 
X 
X 
X 
X 
X 
X 
 
Efficacy 
Assessments 
CDAI patient diary 
Xh 
X 
X 
X 
X 
X 
 
 
CDAI clinical score  
Xh 
X 
X 
X 
X 
X 
 
 
Colonoscopy  
Xh 
 
 
 
Xi 
Xj 
 
 
SES-CD 
Xh 
 
 
 
X 
X 
 
 
Colonic biopsy 
X 
 
 
 
X 
Xj 
 
 

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Trial Procedures 
Screening 
Induction Period 
 
Early Term 
Visit 
Safety Follow-up 
Dose Escalation 
1 mg Dose 
Visit I1 
Visit I2 
Visit I3 
Visit I4 
Day 1a,b 
Week 4b 
Week 8b 
Week 12b,c 
Day-35 
to 0 
Day 1 
Day 28±3 
Day 56±3 
Day 84±3 
Last Dose 
+30 ±3 days 
Last Dose 
+90 
±10 daysr 
 
 
X 
 
 
X 
X 
X 
 
 
Enterocutaneous and 
perianal fistula drainagek 
X 
 
 
 
X 
X 
 
 
PK and PD 
Assessments 
 
 
 
X 
X 
X 
X 
 
 
 
PK blood samplingl  
 
X 
X 
X 
X 
X 
X 
X 
Flow cytometry 
 
X 
 
 
Xm 
X 
 
 
Safety  
Assessments 
Adverse events 
 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
Xn 
 
 
X 
X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
 
Hematologys 
X 
X 
X 
X 
X 
X 
X 
 
Blood chemistry 
X 
X 
X 
X 
X 
X 
X 
 
Pregnancy test  
(WOCBP only)o 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panel 
X 
 
 
 
 
X 
 
 
Urinalysis 
X 
 
X 
 
X 
X 
 
 
Physical examinationp 
X 
X 
X 
X 
X 
X 
X 
 
Pulmonary function 
testsq 
X 
 
 
 
X 
X 
 
 
Optical coherence 
tomography 
X 
 
X 
 
X 
X 
 
 

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a  The duration of Day 1 Visit will be approximately 7 hours.   
b  Trial visits should be scheduled in the morning, where possible, and on trial visit days patients should be instructed to withhold the dose until the trial visit .  The dose should be 
administered during the visit. 
c  Patients should continue taking investigational drug while it is being determined if they qualify for the Extension Period.  Those who do not qualify should return for their Early 
Term Visit as soon as is practical but no later than 4 weeks after their Week 12 visit. 
d  Medical history will include smoking and Crohn’s disease history.  Day 1 medical history can be abbreviated, noting events that occurred between Screening and Day 1. 
e  Active TB must be ruled out according to local medical practices.   
f  Serology testing will be performed at Screening to determine the patient's immune status with respect to the following viruses: Human immunodeficiency virus (HIV) antibodies, 
anti-hepatitis A virus IgM, hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antigen (HBcAg) IgM, anti-hepatitis C virus (HCV) IgG or IgM.  In addition, patients 
must have documentation of positive Varicella Zoster Virus (VZV) IgG antibody status or complete VZV vaccination at least 30 days prior to first dose of investigational drug. 
g  At Screening the stool sample will be used to rule out serious infection and should include evaluation for C. difficile toxin as well as ova and parasitic examination. 
h   During Screening the CDAI clinical score, SES-CD and colonoscopy must be completed within 14 days of Day 1.  Patients should also begin completing the CDAI patient diary 
during this time. At Screening, patients will be issued a CDAI diary and will be trained in the completion of the diary. 
i  Week 12 colonoscopy should be performed either on day of visit or no more than 7 days prior to the visit date. 
j  Colonoscopy does not need to be performed at the Early Term visit if one was completed within 8 weeks of the Early Term visit. 
k  Enterocutaneous and perianal fistula drainage assessment will only be performed on patients with fistulas at baseline. 
l  Blood samples for PK evaluation are to be taken up to 15-30 minutes prior to investigational drug administration (pre-dose) and just prior to discharge from the clinic (6-8 hours 
post-dose) on Day 1.  Blood samples at subsequent visits will be trough level, taken just prior to investigational drug administration. The actual time of investigational drug 
administration for all visits with PK evaluation will be recorded.  The blood sample at the 30-day and 90-day Safety Follow-Up Visit can be collected at any point during the 
visit.  An additional PK sample will be obtained for patients with any AE resulting in discontinuation or SAE. 
m  Week 12 flow cytometry analysis will only be performed for patients with a baseline sample (Day 1). 
n  Prior to first dose of investigational drug, a 12-lead ECG will be performed. After the dose, patients will have hourly vital signs recorded at 1, 2, 3, 4, 5, and 6 hours post-dose.  
A second 12-lead ECG will be performed at the end of the observation period. 
o  For females of childbearing potential only, serum beta hCG is required at screening and a urine beta hCG is required at each visit.  Between scheduled visits up until the 90-day 
Safety Follow-up Visit, monthly urine pregnancy tests should be performed by the patient.  If a urine pregnancy test result is positive, the investigator will instruct the patient to 
suspend further RPC1063 dosing, if applicable, and schedule a follow-up appointment as soon as possible.  A serum pregnancy test will be performed for confirmation, including 
after the 90-day Safety Follow-up Visit, if needed. Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted for female subjects of 
childbearing potential. The Investigator will educate all FCBP about the different options of contraceptive methods or abstinence as appropriate. The subject will be re-educated 
every time her contraceptive measures/methods or ability to become pregnant changes. The female subject’s chosen form of contraception must be effective by the time the 
female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization). 
p  The screening physical examination (PE) includes height and weight, other visits include weight.  A complete PE will be performed at Screening and end of trial visit (Week 12 
or Early Term).  The complete PE will include a full examination of the skin for lesions as well as a check for visual symptoms (i.e., blurred vision or decreased visual acuity).  
An interim PE may be performed at all other visits.  The interim PE will include areas with previously-noted abnormalities and those associated with any new complaints from 
the patient.  The interim PE will also include a check for visual symptoms (i.e., blurred vision or decreased visual acuity). 
q  DLCO, if locally available, will be done at Screening and Early Term. 
r The 90-day Safety Follow-up Visit should be conducted as a clinic visit.  However, if the patient is not available for a clinic visit, a telephone call follow-up should be performed 
(with at least 3 attempts within the visit window) to record the pregnancy test result, concomitant medications, and AEs, including information regarding relationship of AEs to 
RPC1063. 
s  If ALC is confirmed < 200 cells/μL, the Investigator will temporarily discontinue investigational drug. Laboratory testing will be repeated weekly until ALC is > 500 cells/µL.  
For patients whose ALC level is confirmed < 200 cells/μL and has not reached the acceptable range (ALC > 500 cells/µL) during the study, laboratory testing will be repeated at 
the 90-day Safety Follow-up Visit.  
Abbreviations: AE = adverse event; ALC = absolute lymphocyte count; CDAI = Crohn’s Disease Activity Index; DLCO = diffusion capacity of the lung for carbon monoxide; 
Early Term = Early Termination; ECG = electrocardiogram; PD = pharmacodynamic; PK = pharmacokinetic; SES-CD = Simple Endoscopic Score for Crohn’s disease; TB = 
tuberculosis; WOCBP = women of child-bearing potential 

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Table 3: 
Schedule of Events for Extension Period 
 
Trial 
Procedures 
Extension Period 
 
 
Treatment 
 
Safety Follow-
up 
 
E1a,b 
E2b 
E3b 
E4b 
E5b 
E6b 
E7b 
E8b 
E9b 
E10 
E11 
E12 
E13 
E14b 
Early 
Term 
 
W12 
W 
24 
W 
36 
W 
48 
W 52 
W 
64 
W 
76 
W 88 
W 
100 
W 
112 
W 
124 
W 
136 
W 148 
W 
160 
 
Day 84 
±3 
Day 
168 
±7 
Day 
252 
±7 
Day 
336 
±3 
Day 
364 
±3 
Day 
448 
±7 
Day 
532 
±7 
Day 
616 
±7 
Day 
700 
±7 
Day 
784 
±7 
Day 
868 
±7 
Day 
952 
±7 
Day 
1036 
±7 
Day 
1120
±7 
Day of 
Early 
Term 
Last 
dose 
+30 
±3 
days  
Last 
dose 
+90 
±10 
daysj 
 
Dispense 
investigational 
drug 
See Week 12 of the Induction Period 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xk 
 
 
 
 
Administer 
investigational 
drug at clinic 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Review drug 
compliance 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Efficacy Assessments 
CDAI patient 
diary 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CDAI clinical 
score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Colonoscopy 
 
 
 
Xc 
 
 
 
 
 
 
 
 
 
Xd 
 
 
SES-CD score 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Xd 
 
 
Colonic biopsy 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Xd 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 

Sponsor: Celgene International II Sàrl 
 
 
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Efficacy and Safety of RPC1063 in CD 
 
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32 
 
Trial 
Procedures 
Extension Period 
 
 
Treatment 
 
Safety Follow-
up 
 
E1a,b 
E2b 
E3b 
E4b 
E5b 
E6b 
E7b 
E8b 
E9b 
E10 
E11 
E12 
E13 
E14b 
Early 
Term 
 
W12 
W 
24 
W 
36 
W 
48 
W 52 
W 
64 
W 
76 
W 88 
W 
100 
W 
112 
W 
124 
W 
136 
W 148 
W 
160 
 
Day 84 
±3 
Day 
168 
±7 
Day 
252 
±7 
Day 
336 
±3 
Day 
364 
±3 
Day 
448 
±7 
Day 
532 
±7 
Day 
616 
±7 
Day 
700 
±7 
Day 
784 
±7 
Day 
868 
±7 
Day 
952 
±7 
Day 
1036 
±7 
Day 
1120
±7 
Day of 
Early 
Term 
Last 
dose 
+30 
±3 
days  
Last 
dose 
+90 
±10 
daysj 
Enterocutaneous 
and perianal 
fistula drainagee 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
PK and PD 
Assessments 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
 
PK blood 
samplingf 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
Safety Assessments 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hematologyl 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Blood chemistry 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Urine pregnancy 
testg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Physical 
Examinationh 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pulmonary 
function testi 
 
X 
 
 
X 
 
 
 
 
X 
 
 
 
X 
X 
 
 

Sponsor: Celgene International II Sàrl 
 
 
Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
33 
 
Trial 
Procedures 
Extension Period 
 
 
Treatment 
 
Safety Follow-
up 
 
E1a,b 
E2b 
E3b 
E4b 
E5b 
E6b 
E7b 
E8b 
E9b 
E10 
E11 
E12 
E13 
E14b 
Early 
Term 
 
W12 
W 
24 
W 
36 
W 
48 
W 52 
W 
64 
W 
76 
W 88 
W 
100 
W 
112 
W 
124 
W 
136 
W 148 
W 
160 
 
Day 84 
±3 
Day 
168 
±7 
Day 
252 
±7 
Day 
336 
±3 
Day 
364 
±3 
Day 
448 
±7 
Day 
532 
±7 
Day 
616 
±7 
Day 
700 
±7 
Day 
784 
±7 
Day 
868 
±7 
Day 
952 
±7 
Day 
1036 
±7 
Day 
1120
±7 
Day of 
Early 
Term 
Last 
dose 
+30 
±3 
days  
Last 
dose 
+90 
±10 
daysj 
Optical 
coherence 
tomography 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
X 
 
 
a  The duration of Visit E1 will be approximately 3 hours.   
b  Trial visits should be scheduled in the morning, when possible.  At trial Visits Week 24, 52 and at Week 160, patients should be instructed to withhold the dose until the trial 
visit and the dose should be administered during the visit. 
c  At Week 52, a colonoscopy should be performed either on the day of visit or no more than 7 days prior to the visit date. 
d  Colonoscopy, biopsy, and SES-CD score do not need to be performed at the Early Term visit if the Early Term Visit occurs within 8 weeks of the Week 12 colonoscopy or after 
the Week 52 colonoscopy assessment. 
e  Enterocutaneous and perianal fistula drainage assessment will only be performed on patients with fistulas at baseline. 
f  Blood samples at each visit will be trough level, taken just prior to investigational drug administration.  The actual time of investigational drug administration for all visits with 
PK evaluation will be recorded.  The blood sample at the Follow-up visit can be collected at any point during the visit.  An additional PK sample will be obtained for patients 
with any AE resulting in discontinuation or SAE. 
g  For females of childbearing potential only, serum beta hCG is required at screening and a urine beta hCG is required at each visit.  Between scheduled visits up until the 90-day 
Safety Follow-up Visit, monthly urine pregnancy tests should be performed by the patient.  If a urine pregnancy test result is positive, the investigator will instruct the patient to 
suspend further RPC1063 dosing, if applicable, and schedule a follow-up appointment as soon as possible.  A serum pregnancy test will be performed for confirmation, including 
after the 90-day Safety Follow-up Visit, if needed. Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted for female subjects of 
childbearing potential. The Investigator will educate all FCBP about the different options of contraceptive methods or abstinence as appropriate. The subject will be re-educated 
every time her contraceptive measures/methods or ability to become pregnant changes. The female subject’s chosen form of contraception must be effective by the time the 
female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization). 
h  A complete PE will be performed at Week 160 or Early Term, whichever is applicable.  The complete PE will include a full examination of the skin for lesions as well as a check 
for visual symptoms (i.e., blurred vision or decreased visual acuity).  An interim physical examination may be performed at all other visits; weight will be recorded at all visits.  
The interim PE will include areas with previously-noted abnormalities and those associated with any new complaints from the patient.  The interim PE will also include a check 
for visual symptoms (i.e., blurred vision or decreased visual acuity). 
i  DLCO, if locally available, will be done at Week 52 and Early Term. 
j  The 90-day Safety Follow-up Visit should be conducted as a clinic visit.  However, if the patient is not available for a clinic visit, a telephone call follow-up should be performed 
(with at least 3 attempts within the visit window) to record the pregnancy test result, concomitant medications, and AEs, including information regarding relationship of AEs to 
RPC1063. 

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k  For eligible patients who are entering the Phase 3 open-label extension CD Study RPC01-3204 at a future date (not on visit Week 160), investigational drug will be dispensed in 
this study. For eligible patients who are immediately entering the Phase 3 open label extension CD Study RPC01-3204 on the same day as visit Week 160, investigational drug 
will be dispensed in Study RPC01-3204. 
l  If ALC is confirmed < 200 cells/μL, the Investigator will temporarily discontinue investigational drug. Laboratory testing will be repeated weekly until ALC is > 500 cells/µL.  
For patients whose ALC level is confirmed < 200 cells/μL and has not reached the acceptable range (ALC > 500 cells/µL) during the study, laboratory testing will be repeated at 
the 90-day Safety Follow-up Visit.  
Abbreviations:  AE = adverse event; ALC = absolute lymphocyte count; CD = Crohn’s disease; CDAI = Crohn’s Disease Activity Index; DLCO = diffusion capacity of the lung 
for carbon monoxide; Early Term = Early Termination; ECG = electrocardiogram; PK = pharmacokinetic; PD = pharmacodynamic; SES-CD = Simple Endoscopic Score for 
Crohn’s disease 
 

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Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
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8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
8.1. 
Patient Inclusion Criteria 
To be eligible to participate in this trial, candidates must meet the following inclusion criteria: 
1. Male or female patients aged 18 to 75 years, inclusive  
2. Diagnosis of Crohn’s disease for at least 2 months (prior to Screening) by clinical 
endoscopic evidence and corroborated by a histology report (Note:  histopathology may 
be performed during Screening if no prior report is readily available). 
3. Crohn’s disease Activity Index score of 220 to 450 inclusive with an SES-CD score of 
≥ 6.  (If disease isolated to ileum, the requirement will be a SES-CD score ≥ 4.) 
4. Average daily stool score ≥ 4 points and/or an average daily abdominal pain score of 
≥ 2 points. 
5. Patients must meet one of the following criteria: 
 Have an inadequate response or loss of response to at least one of the following 
Crohn’s disease treatments : 
 Aminosalicylates, oral aminosalicylates ≥2.4 g/day or ≥3 g/day sulfasalazine for 
at least 4 weeks 
 Corticosteroids, oral prednisone ≥30 mg or budesonide ≥9 mg for at least 2 weeks 
or an equivalent (to oral prednisone) of intravenous corticosteroid for 1 week 
 Immunomodulators, oral azathioprine ≥ 1.5 mg/kg or 6-mercaptopurine 
0.75 mg/kg (documentation of therapeutic level of 6-thioguanine is also 
acceptable) or methotrexate ≥ 12.5 mg/week for at least 8 weeks 
 Biologic therapy (TNF antagonist or vedolizumab only) at an approved labeled 
dose used for induction therapy for at least 4 weeks or recurrence of disease 
activity despite scheduled maintenance therapy.  (Biologic therapy exposed 
patients will be capped at 50% of total enrolled patients) 
 And/or have been intolerant to any of the above mentioned therapies (e.g., unable to 
achieve doses, dose levels, or treatment durations because of treatment related side 
effects and/or laboratory abnormalities) 
6. The following background therapies for Crohn’s disease will be permitted on a stable 
dose: 
 Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide) at a 
stable dose for at least 3 weeks prior to Screening endoscopy  
 Prednisone (doses ≤ 20 mg per day) or equivalent at a stable dose (dose ≤ 9 mg per 
day) for at least 2 weeks prior to Screening endoscopy 
 Budesonide therapy at a stable dose for at least 2 weeks prior to Screening endoscopy 

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 Antibiotics used for the treatment of Crohn’s disease (i.e., ciprofloxacin, 
metronidazole) at a stable dose for at least 2 weeks prior to Screening endoscopy 
7. If oral aminosalicylates or corticosteroids have been recently discontinued, they must 
have been stopped for at least 2 weeks prior to the endoscopy used for baseline 
endoscopy score 
8. Female patients of childbearing potential: 
Must agree to practice a highly effective method of contraception throughout the trial 
until completion of the 90-day Safety Follow-up Visit. Highly effective methods of 
contraception are those that alone or in combination result in a failure rate of a Pearl 
index of less than 1% per year when used consistently and correctly. Acceptable methods 
of birth control in the trial are the following: 
 combined hormonal (oestrogen and progestogen containing) contraception, which 
may be oral, intravaginal, or transdermal  
 progestogen-only hormonal contraception associated with inhibition of ovulation, 
which may be oral, injectable, or implantable 
 placement of an intrauterine device (IUD) 
 placement of an intrauterine hormone-releasing system (IUS) 
 bilateral tubal occlusion 
 vasectomised partner 
 complete sexual abstinence  
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal 
(coitus interruptus), spermicides only, and lactational amenorrhoea method are not 
acceptable methods of contraception. Female condom and male condom should not be 
used together.  
Counseling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted for female subjects of childbearing potential. The Investigator will educate all 
FCBP about the different options of contraceptive methods or abstinence as appropriate. 
The subject will be re-educated every time her contraceptive measures/methods or ability 
to become pregnant changes. The female subject’s chosen form of contraception must be 
effective by the time the female subject is randomized into the study (for example, 
hormonal contraception should be initiated at least 28 days before randomization). 
9. Ability to provide written informed consent and to be compliant with the schedule of 
protocol assessments 
10. Must have documentation of positive Varicella zoster virus (VZV) immunoglobulin G 
(IgG) antibody status or complete VZV vaccination at least 30 days prior to first dose of 
investigational drug 
11. For patients at high risk (i.e., family history, disease duration) for colonic malignancy, 
documented evidence of having had a surveillance colonoscopy within the last 2 years or 
according to local medical guidelines to evaluate for polyps, dysplasia, or malignancy.  

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If no recent history of surveillance colonoscopy, this can be done as part of colonoscopy 
performed during Screening 
8.2. 
Patient Exclusion Criteria 
Candidates will be excluded from entering the trial if any of the following exclusion criteria exist 
at time of enrollment or at the time point specified in the individual criterion listed: 
Exclusions Related to General Health: 
1. Diagnosis of ulcerative colitis or indeterminate colitis 
2. Crohn’s disease isolated to the stomach, duodenum, jejunum, or peri-anal region, without 
colonic or ileal involvement 
3. Known strictures or stenosis leading to symptoms of obstruction 
4. Current stoma or need for ileostomy or colostomy 
5. Extensive small bowel resection (>100 cm) or known diagnosis of short bowel syndrome 
6. Suspected or diagnosed intra-abdominal or perianal abscess that has not been 
appropriately treated 
7. Currently require or are anticipated to require surgical intervention for Crohn’s disease 
during the Induction Period 
8. Currently receiving total parenteral nutrition 
9. Positive stool culture for pathogens (ova and parasites, bacteria) or positive test for 
Clostridium difficile (C. difficile) at Screening.  Patients may be treated and retested but 
must have negative stool culture for pathogens (ova and parasites, bacteria) within 
30 days prior to first dose of investigational drug and 60 days prior to first dose of 
investigational drug for C. difficile 
10. Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG) 
measured during Screening 
11. Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, 
psychiatric or other major systemic disease making implementation of the protocol or 
interpretation of the trial difficult or that would put the patient at risk by participating in 
the trial 
12. Clinically relevant cardiovascular conditions, including history or presence of: 
 Recent (within the last 6 months) occurrence of myocardial infarction, unstable 
angina, stroke, transient ischemic attack, decompensated heart failure requiring 
hospitalization, Class III/IV heart failure, sick sinus syndrome, or severe untreated 
sleep apnea 
 Prolonged QTcF interval (QTcF > 450 msec males, > 470 msec females), or at 
additional risk for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital 
long-QT syndrome) 

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Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
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 Resting HR less than 55 beats per minute (bpm) when taking vitals as part of a 
physical examination at Screening 
 Mobitz type 2nd degree or 3rd degree AV block 
13. History of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with 
hemoglobin A1c > 9%, or diabetic patients with significant co-morbid conditions such as 
retinopathy or nephropathy 
14. History of uveitis or known macular edema 
15. Known active bacterial, viral, fungal, mycobacterial infection, or other infection 
(including tuberculosis [TB] or atypical mycobacterial disease [but excluding fungal 
infection of nail beds, minor upper respiratory tract infections and minor skin infections]) 
or any major episode of infection that required hospitalization or treatment with 
intravenous antibiotics within 30 days of Screening or oral antibiotics within 14 days of 
Screening.   
16. History or known presence of recurrent or chronic infection (eg, hepatitis A, B, or C, 
human immunodeficiency virus (HIV); recurrent urinary tract infections are permitted. 
17. History of cancer, including solid tumors and hematological malignancies (except basal 
cell and in situ squamous cell carcinomas of the skin that have been excised and 
resolved) 
18. Past or current evidence of colonic dysplasia 
19. History of alcohol or drug abuse within 1 year prior to first dose of investigational drug 
20. History of or currently active primary or secondary immunodeficiency 
Exclusions Related to Medications: 
21. History of treatment with a biologic agent within 5 elimination half-lives of that agent 
prior to first dose of investigational drug 
22. History of treatment with an investigational agent within 5 elimination half-lives of that 
agent prior to first dose of investigational drug 
23. History of treatment with topical rectal 5-ASA or steroids within 2 weeks of Screening 
24. History of primary non-response to two approved biologic therapies used for the 
treatment of Crohn’s disease  
25. Receipt of a live vaccine within 4 weeks prior to Screening 
26. Previous treatment with lymphocyte-depleting therapies (e.g., Campath, anti-CD4, 
cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body 
irradiation, bone marrow transplantation, alemtuzumab, daclizumab) 
27. Treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 
16 weeks of Screening 
28. Previous treatment with D-penicillamine, leflunomide, or thalidomide 
29. Previous treatment with natalizumab or fingolimod 

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30. History of treatment with intravenous immune globulin (IVIg), plasmapheresis, within 
3 months prior to first dose of investigational drug 
31. Planned concurrent treatment with immunosuppressive agents (e.g., azathioprine, 6-MP, 
or methotrexate) after enrollment.  Patients receiving azathioprine, 6-MP or methotrexate 
at Screening must discontinue treatment with these agents prior to first dose of 
investigational drug. 
32. Chronic non-steroidal anti-inflammatory drug (NSAID) use (Note: occasional use of 
NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and 
aspirin up to 325 mg/day is permitted) 
33. Treatment with Class Ia or Class III anti-arrhythmic drugs) or treatment with two or more 
agents in combination known to prolong PR interval 
34. Treatment with any of the following drugs or interventions within the corresponding 
timeframe: 
 At Day 1   
 CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin) 
 Two weeks prior to Day 1 
 Monoamine oxidase inhibitors (eg, selegiline, phenelzine)  
Exclusions Related to Laboratory Results: 
35. Serum creatinine  1.4 mg/dL for women or  1.6 mg/dL for men 
36. Liver function impairment or persisting elevations of aspartate aminotransferase (AST) or 
alanine aminotransferase (ALT)  2 times the upper limit of normal (ULN), or direct 
bilirubin  1.5 times the ULN 
37. Platelet count  100,000/μL 
38. Hgb  8.5 g/dL 
39. Neutrophils < 1500/μL 
40. Absolute WBC count < 3500/μL 
41. Absolute lymphocyte count < 800/μL 
42. Electrocardiogram showing any clinically significant abnormality (e.g., acute ischemia, 
any significant heart conduction abnormality [e.g., left bundle branch block]) 
43. Forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC) < 70% of 
predicted values at Screening 
8.3. 
Trial Discontinuation 
Patients will be encouraged to complete the trial; however, they may voluntarily withdraw at 
any time.  The Investigator will provide a written explanation in the source documentation to be 
entered on the appropriate eCRF page describing the reason for discontinuation. 

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Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
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The criteria for enrollment are to be followed explicitly.  If a patient who does not meet 
enrollment criteria is inadvertently enrolled, the Medical Monitor must be contacted, and that 
patient will be withdrawn from the trial if continuation is determined to be a safety risk. 
Reasons for discontinuation include, but are not limited, to the following: 
 Physician decision:  The Investigator must discontinue investigational drug if it is 
determined that it is not safe or in the patient’s best interest to receive further 
treatment.  The Medical Monitor should be promptly notified of the decision 
 Non-compliance with investigational drug:  After consultation between the 
Investigator, the Medical Monitor, or Clinical Monitor, and the Sponsor when 
appropriate, a patient may be discontinued from the trial for failure to comply with 
dosing regimen as specified by the protocol 
 Non-compliance with protocol/protocol deviation:  A patient fails to follow protocol 
procedures, or other event or decision that stands in contrast to the guidelines set in 
the protocol 
 Adverse event:  A patient must be discontinued from investigational drug if, in the 
judgment of the Investigator or if specified in the protocol, the patient develops an 
AE such as an intercurrent illness or complication that justifies discontinuation of 
investigational drug 
 Lack of efficacy: Decision by the patient and/or the Investigator to discontinue 
treatment due to a lack of expected or desired effect related to a therapy 
 Withdrawal by Patient:  The patient may choose to discontinue investigational drug at 
any time.  Every effort should be made within the bounds of safety and patient choice 
to have each patient complete the Early Termination Visit and 30-day and 90-day 
Safety Follow-up Visits.  If a patient withdraws consent, the only additional trial data 
to be collected will be the follow-up of SAEs as mandated by the protocol 
 Pregnancy: If the patient becomes pregnant investigational drug must be discontinued 
(see Section 12.2.11 ) 
 Trial termination by Sponsor 
 Other 
All patients who discontinue the trial should complete an Early Termination Visit (see Table 2 
and Table 3).  For subjects who have a confirmed ALC below the 200 cells/μL limit and 
permanently discontinue from participation in the study, central laboratory testing will continue 
every 14 days (± 3 days) after the Early Termination Visit until it is above the lower limit of 
normal.  With the exception of patients who withdraw consent or are lost to follow-up, patients 
should complete the 30-day and 90-day Safety Follow-up Visits for the collection of safety data 
and to assess their disease status.  Alternative treatment for CD can be started, if needed, after the 
Early Termination Visit. 
The reason for discontinuation of investigational drug will be recorded in the clinical records and 
the patient’s eCRF.  For those patients whose status is unclear because they fail to appear for trial 
visits without stating an intention to discontinue trial participation, the Investigator should 

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Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
41 
document in the source documents the steps taken to contact the patient (e.g., dates of telephone 
calls, registered letters) prior to withdrawing the patient from the trial. 
Patients who withdraw from the trial will not be replaced. 

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Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
42 
9. 
TRIAL TREATMENTS 
The Investigator must ensure that the investigational drug will be used only in accordance with 
the protocol.  Investigational drug should not be used for purposes other than as defined in this 
protocol. 
9.1. 
Treatments Administered 
 
 
 
 
 
 
 
9.1.1. 
Instructions for Missed Dose(s) of RPC1063 Capsules 
 
 
 
 
 
 
 
 
 
 
9.1.2. 
Induction Period 
Patients will receive RPC1063 1 mg oral capsule daily for 11 weeks after the 7-day dose 
escalation (12 weeks total duration). 
9.1.3. 
Extension Period 
All patients will receive RPC1063 1 mg capsule orally once daily for 148 weeks. 
9.2. 
Selection of Dose in the Trial 
The selected dose of 1 mg/day of RPC1063 is primarily based on the results from the Phase 2 
dose finding induction trial in UC (RPC01-202).  The 1 mg/day dose demonstrated better 
efficacy than the 0.5 mg/day dose across various clinical and endoscopic endpoints.   
Furthermore, the expected magnitude of pharmacodynamics effect on peripheral lymphocyte 
reduction and an acceptable safety profile was observed.  
A dose escalation over the first 7 days (0.25 mg/day on Days 1 to 4 and 0.5 mg/day 
[administered as two 0.25 mg capsules] on Days 5 to 7) will be implemented, as results from 
RPCS 001 and preliminary results from RPC01-202 indicate that use of a dose escalation 

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Protocol No. RPC01-2201 
Efficacy and Safety of RPC1063 in CD 
 
24 May 2019, Version 5.0 
 
Confidential 
43 
regimen mitigates the magnitude of reduction in HR.  Preliminary evidence from these trials 
suggest that patients who increase their dose progressively over the first week are less likely to 
have a clinically meaningful decrease in HR or blood pressure; therefore, a dose escalation 
starting with 0.25 mg RPC1063 for the first 4 days of dosing followed by 0.5 mg (administered 
as two 0.25 mg capsules) on Days 5 through 7 before progressing to the 1 mg/day dose will be 
used. 
9.3. 
Method of Assigning Patients to Treatment Groups 
Not applicable. 
9.4. 
Selection and Timing of Dose for Each Patient 
Patients will self-administer RPC1063 orally once-daily.  Investigational drug should be taken at 
approximately the same time each day with or without food. 
9.5. 
Prior and Concomitant Treatments 
All treatments, other than RPC1063, being taken by the patients on entry into the trial or at any 
time during the trial including through the 90-day Safety Follow-up Visit, are regarded as 
concomitant medications and must be documented on the appropriate section of the eCRF.  A 
history of all prior medications needs to be documented to at least 4 weeks prior to trial 
participation.  A history of previous treatments for CD needs to be documented. 
Patients who are receiving oral 5-ASA, oral corticosteroids, or purified medicinal probiotics at 
screening must keep their prescribed dosage steady through Week 8 and can only be 
discontinued or reduced in dose if Investigator judgment requires it because of toxicity or 
medical necessity.  After Week 8 these medications can be discontinued or reduced as medically 
indicated.  Oral 5-ASA, oral corticosteroids, or purified medicinal probiotics should not be 
started during the first 12 weeks of the study in patients who were not receiving them during 
screening.  Ideally, patients receiving 5-ASA or purified medicinal probiotics should maintain a 
stable dose throughout the trial. Patients not receiving oral 5-ASA, oral corticosteroids, or 
purified medicinal probiotics at screening can only begin dosing with these medications if 
Investigator judgment requires it because of medical necessity.  
9.5.1. 
Steroid Taper 
During the Induction Phase, patients are to maintain their stable baseline corticosteroid dose, if 
applicable. 
Corticosteroids may be tapered starting from Week 12 for patients entering the Extension Period.  
Patients receiving prednisone at a dose of > 10 mg/day (or equivalent) may have their dose 
reduced at a rate of 5 mg per week until a 10 mg/day dose is achieved.  Patients receiving 
prednisone at doses of ≤ 10 mg/day (or equivalent), or once a 10 mg/day dose (or equivalent) is 
achieved by tapering, may have their dose reduced at a rate of 2.5 mg/week until discontinuation.  
Beginning at Week 12, patients receiving budesonide may taper their dose at a rate of 3 mg every 
3 weeks.  For patients who do not tolerate a corticosteroid taper without recurrence of clinical 
symptoms of either CD or steroid withdrawal, the corticosteroid dose may be increased (up to the 
dose at trial entry if required), but tapering may be tried again. 

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9.5.2. 
Allowed Medications 
All prior medications (including over-the-counter medications) administered 30 days prior to the 
first dose of investigational drug and any concomitant therapy administered to the patient during 
the course of the trial (starting at the date of informed consent) until 90 days after the final dose 
of investigational drug will be recorded.  Additionally, all diagnostic, therapeutic, or surgical 
procedures and/or past biologic exposure relating to CD should be recorded.  Any medication 
that is considered necessary for the patient’s health and that is not expected to interfere with the 
evaluation of or interact with investigational drug may be continued during the trial 
(see Table 4). 
Administration of concomitant medications must be reported in the appropriate section of the 
eCRF along with dosage information, dates of administration, and reasons for use.  For 
medications with a single active ingredient, generic names for concomitant medication should be 
used if possible.  For combination products, brand names should be used.  The total daily dose 
should be filled in whenever possible. 
9.5.3. 
Concomitant Medications Prohibited Through the 30-Day Safety Follow-up Visit 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
  
 
 
  
 
 
 
 
 
  
 
 
 
  
 
  
 
 
 
  

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Table 4: 
Examples of Prohibited Cardiac Medications (Systemic Use) 
Pharmaceutical Class 
Example Medications 
Anti-arrhythmic drugs 
Amiodarone, bepridil hydrochloride, disopyramide, dofetilide, dronedarone, 
flecainide, ibutilide, sotalol, lidocaine, procainamide, propafenone, quinidine, 
tocainide 
9.5.4. 
Concomitant Medications Between the 30-Day Safety Follow-up Visit and the 
90-Day Safety Follow-up Visit 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
9.6. 
Medical Care of Patients after End of Trial 
Patients who leave the trial and complete their end of trial assessments, including the 30-day and 
90-day Safety Follow-up Visits, do not require any additional care provided by the sponsor; they 
will return to the care of their personal physician(s). 
9.7. 
Treatment Compliance 
It is the Investigator’s responsibility to ensure that patients are correctly instructed on how to 
take their investigational drug and that each patient is fully compliant with their assigned dosage 
regimen.  Records of investigational drug used and intervals between visits will be kept during 
the trial.  Drug accountability will be noted by the Clinical Monitor during site visits and at the 
completion of the trial.  Patients will be asked to return all unused medication at the end of the 

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trial.  The investigational drug should be dispensed by the Investigator, or by a qualified 
individual under the Investigator’s supervision.  An up-to-date treatment inventory/dispensing 
record must be maintained as described in Section 10.3.  
Overall trial non-compliance is defined as taking less than 80% or more than 120% of 
investigational drug during the entire treatment period. 
At each visit, previously dispensed investigational drug capsules will be collected by the 
Investigator, or by a qualified individual under the Investigator’s supervision, and compliance 
assessed.  Patients exhibiting poor compliance as assessed by medication counts (i.e., 2 or more 
missed medication days in 1 week) and their response to a medication compliance question at 
each visit should be counseled on the importance of good compliance to the trial dosing regimen.  
Patients who are persistently non-compliant (<80% or >120%) should be discussed with the 
Medical Monitor to determine whether they should be withdrawn from the trial. 
9.8. 
Blinding 
This is an open-label trial without randomization. 

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10. 
INVESTIGATIONAL DRUG MATERIALS AND MANAGEMENT 
10.1. 
Investigational Drug 
 
   
 
 
 
 
 
 
 
 
10.2. 
Packaging and Labeling 
RPC1063 capsules will be packaged in 30 cc white high-density polyethylene bottles 
(35 capsules per bottle, apart from the dose escalation kits), closed with a 28 mm child resistant 
screw-cap that is induction sealed.  The labeling of investigational drug will be in accordance 
with GCP and any other local regulatory requirements. 
10.3. 
Investigational Drug Accountability 
Investigational drug should not be used for purposes other than as defined in this protocol. 
All supplies of investigational drug will be accounted for in accordance with GCP.  There will 
be an individual investigational drug accountability record for each patient and the Investigator 
should maintain accurate records of the disposition of all investigational drug supplies received 
during the trial.  These records should include the amounts and dates clinical drug supplies were 
received, dispensed to the patient, returned by the patient and returned to the Sponsor.  If errors 
or damages in the clinical drug supply shipments occur, the Investigator should contact the 
Clinical Monitor immediately.  Each Investigator will provide copies of the investigational drug 
accountability records for inclusion in the Trial Master File after database lock.  The Clinical 
Monitor will periodically check the supplies of investigational drug held by the Investigator or 
pharmacist to verify accountability of all investigational drug used. 
The Investigator will provide the investigational drug only to the identified patients of this trial, 
according to the procedures described in this trial protocol.  After the end of the trial, the Clinical 
Monitor will perform final accountability, package, seal, and prepare for shipment.  
Investigational drug and all medication containers will be returned to the clinical supply 
distribution vendor and documentation will be returned to the CRO.  The CRO will verify that a 
final report of investigational drug accountability is prepared and maintained in the Investigator’s 
Trial Center File. 

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11. 
ASSESSMENT OF EFFICACY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS 
11.1. 
Efficacy Assessments 
11.1.1. 
Primary Efficacy Assessments 
The SES-CD will be used to evaluate the primary efficacy endpoint. 
11.1.2. 
SES-CD 
The simple endoscopy score (SES-CD) assesses the degree of inflammation.  The SES-CD 
assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and 
presence of narrowing.  Each of these components are scored on a scale of 0 to 3 as outlined in 
Table 5. 
In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and 
colon:  ileum, right, transverse, left (descending and sigmoid), and rectum.  The SES-CD is the 
sum of the individual scores of each of the components across the five segments.  Mild CD is 
defined as an SES-CD ≥3 but less than 7 points.  Moderate to severely active CD is defined as 
an SES-CD of ≥7 points.  
To ensure quality data and standardization, the same endoscopist should be used throughout the 
trial wherever possible.  Colonoscopies will be read at a centralized reading facility.  Each 
patient who enters into the trial will have colonic biopsies obtained during colonoscopy (see 
Table 2 and Table 3).  Details regarding the biopsies are provided in the biopsy manual. 
Table 5: 
Definitions of Simple Endoscopic Score for Crohn's Disease 
 
SES-CD Values 
Variable 
0 
1 
2 
3 
Size of ulcers 
None 
Aphthous ulcers  
(< 0.5 cm) 
Large ulcers  
(0.5 to 2 cm) 
Very large ulcers 
(>2 cm) 
Ulcerated surface 
None 
<10% 
10-30% 
>30% 
Affected surface 
Unaffected 
segment 
<50% 
50-75% 
>75% 
Presence of 
narrowings 
None 
Single, can be 
passed 
Multiple, can be 
passed 
Cannot be passed 
11.1.3. 
Crohn’s Disease Activity Index 
The Crohn’s Disease Activity Index (CDAI) is a composite score that is used to measure the 
clinical activity of Crohn’s disease.  The CDAI uses a questionnaire with responses scored 
numerically and weighted.  Scores range from 0 to approximately 600, with higher scores 
indicating greater disease activity.  The 8 components used to assess the CDAI and their 
weighting factors are noted in Table 6.  The definitions of mild, moderate, and severe Crohn’s 
disease are provided in Table 7. 

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Patient-reported outcomes (stool frequency and abdominal pain components of the CDAI Score 
and general well-being), and the other CDAI components will be collected in an electronic diary.  
Patients will complete the stool frequency, abdominal pain and general well-being components 
of the CDAI from the patient’s first screening visit and will continue throughout the trial. 
Patients will be instructed on the use and completion of questions on the electronic diary. 
The diary entries will be reviewed by site personnel during screening (prior to dosing, if 
applicable) and during all trial visits.  The stool frequency and abdominal pain diary entries 
preceding each trial visit will be used to calculate the CDAI score and will be calculated using 
the stool frequency and the abdominal pain data from the most recent 7 day period, or at least 
3 days within that 7 day period, prior to the visit, excluding the following: 
 One day prior to the start of a procedure or preparation for a procedure that would 
affect stool frequency  
 The day(s) of a procedure or preparation for a procedure that would affect stool  
frequency  
Because the colonoscopy preparations can interfere with the assessment of other clinical 
parameters, diary entries used to calculate the CDAI score will not correspond to day(s) of 
bowel preparation or endoscopy. 
Table 6: 
CDAI Assessment 
Clinical or Laboratory Variable 
Weighting Factor, × 
Number of liquid or soft stools each day for 7 days 
2 
Abdominal pain (graded from 0-3 on severity) each 
day for 7 days 
5 
General well-being, assessed from 0 (well) to 4 
(terrible) daily for 7 days 
7 
Presence of complications* 
20 
Taking diphenoxylate/atropine, loperamide, or 
opiates for diarrhea 
30 
Presence of an abdominal mass (0 as none, 2 as 
questionable, 5 as definite) 
10 
Hematocrit 47-HCT in men and 42-HCT in women 
6 
Percentage deviation from standard weight 
1 
Total Score 
 
*One point each is added for each set of complications: arthritis or arthralgia; iritis or uveitis; erythema nodosum, 
pyoderma gangrenosum, aphthous stomatitis; anal fissure, fistula or perirectal abscess; other bowel-related fistula; 
febrile (fever) episode over 100 degrees during the past week 

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Table 7: 
Crohn's Disease Severity Definitions 
Severity 
CDAI Score 
Mild 
150-220 
Moderate 
220-450 
Severe 
>450 
11.1.4. 
PRO2 
The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or 
soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days 
(Khanna 2015).  The components of the score and their relative weightings are included 
in Table 8. 
Table 8: 
PRO 2 Assessment 
Component 
Weighting, x 
Number of liquid or soft stools/day for 7 days 
2 
Abdominal pain (0-3) for 7 days 
5 
The PRO2 assessment will utilize the two components of the CDAI: number of liquid or soft 
stools and abdominal pain. 
11.1.5. 
Un-weighted Stool Frequency and Abdominal Pain 
Stool Frequency as described in Table 8 will be obtained and calculated without a weighting 
factor for use as part of the inclusion criteria (4). Abdominal pain will also be obtained and 
calculated without a weighting factor for use as part of the inclusion criteria (4).  These 
un-weighted patient reported assessments will also be used as efficacy endpoints 
(Section 11.1.7). 
11.1.6. 
Other Efficacy Measures 
11.1.6.1. Enterocutaneous and Perianal Fistula Drainage Assessment 
Fistulas will be characterized as actively draining and open or closed.  Based on physical 
examination, a fistula will be considered open if an investigator can express purulent material 
from the fistula with application of gentle pressure (Present 1999). 
11.1.7. 
Efficacy Definitions 
Endoscopic 
Response: SES-CD decrease from baseline of ≥ 50% 
Remission: SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points with no SES-CD sub-score 
> 1 point 

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CDAI 
Clinical Response: CDAI reduction from baseline of ≥ 100 points 
Clinical Remission: CDAI score of < 150 
PRO2 
Clinical Response:  PRO2 decrease ≥50% 
Clinical Remission:  Average daily stool score ≤ 3 points AND average daily abdominal pain 
score ≤ 1 point 
Mucosal Healing:  Endoscopic remission plus histologic improvement 
11.2. 
Pharmacokinetics and Pharmacodynamics 
11.2.1. 
Pharmacokinetics and Pharmacodynamics 
Pharmacokinetic samples will be shipped to the central laboratory.  Details of the procedures 
to be followed for sample collection, storage, and shipment will be documented in a separate 
laboratory manual.  The actual time of investigational drug administration for all visits with PK 
evaluation will be recorded on the dosing log. 
The following PK and PD assessments will be performed on the visit days specified in Table 2 
and Table 3 to determine the safety profile of RPC1063: 
 Standard PK sampling: Samples on trial will be collected prior to dose administration 
(trough samples) and 6 to 8 hours after dose administration, as indicated in the 
Schedule of Assessments footnotes. 
 Intestinal mucosa: immunohistochemistry and/or in situ hybridization (IHC/ISH) for 
example CD20, CD4, CD8, Foxp3, 47, CCR7, IFN, IL17 
 Intestinal mucosa: transcript profiling (mRNA) for example IFN signature, T cell 
exhaustion signature, outcome signature, S1PR pathway  
 
 
 
 
 
 
11.2.2. 
Flow Cytometry 
Flow cytometry samples will be collected as specified in Table 2. 

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12. 
ASSESSMENT OF SAFETY 
12.1. 
Safety Parameters 
Safety will be evaluated by the incidence, severity, relationship and type of AEs, SAEs, AEs 
leading to discontinuation of investigational drug, and AEs of special interest; and clinically 
meaningful changes from baseline in clinical laboratory test results, vital signs, ECGs, and 
physical examinations. 
12.1.1. 
Physical Examination 
A complete physical examination will include evaluation of heart, lung, head and neck, 
abdomen, skin, and extremities.  All significant findings that are present at baseline must be 
reported on the relevant medical history/current medical conditions eCRF.  Significant findings 
made after enrollment that meet the definition of an AE must be recorded on the AEs eCRF. 
12.1.2. 
Vital Signs 
Systolic and diastolic blood pressure and pulse will be assessed in a sitting position.  An 
automated validated device may be used, if available. In case the cuff sizes available are not 
large enough for the patient's arm circumference, a sphygmomanometer with an appropriately 
sized cuff may be used. 
Patients will be carefully monitored after the first dose of investigational drug with a 6-hour 
post-dose monitoring period of hourly recording of pulse and blood pressure as described in 
Section 12.1.9. 
12.1.3. 
Electrocardiogram 
The 12-lead digital ECG devices will be provided to each clinical site by the central ECG 
laboratory for the duration of the trial.  Detailed instructions describing the process for recording 
and transmission of the digital ECGs will be outlined in the trial-specific manual and provided to 
the site before the start of the trial.  Paper versions of ECG tracings recorded at the times 
specified in the schedule of assessments (Section 7.3, Table 2, and Table 3) will be printed and 
photocopied to preserve the ink if necessary, and kept at the site as source documentation. 
ECG will be performed after the patient has been resting quietly in a supine position.  The 
screening ECG report from the central reader must be available to confirm patient eligibility 
before enrollment.  Electrocardiograms will be performed on Day 1 for all patients while in the 
clinic before the first dose of investigational drug administration and after the 6-hour post-dose 
vital signs assessment.  The 6-hour post-dose ECG will be evaluated by the treating physician, 
with input if needed from a local cardiologist or a central reader to confirm if extended 
monitoring is required.  Additional ECG monitoring will be performed on Days 5 and 8 if 
cardiac issues are identified on the prior day of dose escalation, as described in Section 12.1.9. 
Only clinically significant abnormalities should be reported in the medical history/current 
medical conditions or adverse event CRF.  Clinically significant findings must be discussed with 
the Medical Monitor before enrolling the patient in the trial. 

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12.1.4. 
Ophthalmological Examination 
An OCT will be performed as scheduled in Table 2 and Table 3.  If there is a suspicion of new 
onset or worsening macular edema, then general retinal examinations, including eye history, 
visual acuity, and dilated ophthalmoscopy will be obtained.  A general ophthalmologist can do 
the examination, although a retinal specialist would be preferred to do the examinations 
wherever possible. 
12.1.5. 
Pulmonary Function Tests 
Pulmonary function tests including forced expiratory volume in one second (FEV1) and forced 
vital capacity (FVC) will be performed as scheduled in Table 2 and Table 3.  In addition, 
diffusion capacity of carbon monoxide (DLCO) measurements will be performed where locally 
available.  DLCO will not be required at sites where there is no local testing facility.  These tests 
will be performed at a qualified pulmonary function laboratory or respiratory department.  Refer 
to the American Thoracic Society/European Respiratory Society guidelines for standardization of 
spirometry and single breath determination of carbon monoxide uptake in the lung 
(MacIntyre 2005; Miller 2005a; Miller 2005b). 
12.1.6. 
Height and Weight 
Height will be measured at Screening only; weight will be measured at each visit. 
12.1.7. 
Monitoring of Adverse Events and Serious Adverse Events 
Throughout the course of the trial, every effort must be made to remain alert to possible AEs or 
SAEs.  Refer to Section 12.2 for definitions of AEs/SAEs, monitoring and reporting.  Refer to 
Section 12.2.7 for AEs of special interest.  
12.1.8. 
Monitoring of Concomitant Therapy 
The use of concomitant medication and procedures will be monitored throughout the trial.  
Refer to Section 9.5.3  for prohibited concomitant therapies. 
12.1.9. 
Guidelines for Monitoring Patients Taking Their First Dose of RPC1063 
On Day 1 of treatment for Induction, careful cardiac monitoring of the patients is required.  
The Investigator is responsible for monitoring the patient following the first intake of the 
investigational drug, as well as managing bradycardia symptoms should they occur.  The 
Investigator must review the baseline pre-dose ECG, pulse, and blood pressure during the 6-hour 
monitoring period, post-dose ECG, and assess discharge status at the time specified in Table 2.  
Baseline pre-dose ECG should be provided by the site and be available for comparison to the 
post-dose ECG in order to determine if criteria requiring extended monitoring are met.  
Resting pulse and blood pressure in the sitting position will be measured at the times specified in 
Table 2 (by the Investigator, an assisting nurse, or other medically qualified staff member).  
When obtaining the pulse and blood pressure before the first dose, the patient should be allowed 
to rest in a seated position at least 10 minutes before taking measurements.  The pulse and sitting 
blood pressure measurements should be repeated 2 additional times (before the first dose of 
investigational drug only).  The lowest pre-dose value of sitting pulse and blood pressure (based 
on systolic blood pressure) will be recorded in the case report form and serve as baseline for 

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comparison to post-dose values.  The repeat measurements will be made at approximately 
2-minute intervals.  For the hourly measurements after investigational drug administration, pulse 
and sitting blood pressure will be measured once and recorded in the eCRF. 
Patients should receive the first dose of investigational drug with or without food before 
12:00 pm (noon) in the clinic, if possible.  The first dose of investigational drug must be 
administered in a setting in which resources to appropriately manage symptomatic bradycardia 
are available.  A member of the Investigator team should be available to monitor the patient for 
the 6-hour monitoring period and will need to report any abnormalities to the Investigator.  
Atropine and epinephrine or isoproterenol need to be readily available to the site personnel. 
If any of the following criteria are met, additional extended monitoring (described below) should 
be instituted until the finding has resolved.  Baseline and hourly vital signs measurements 
(Hours 1 through 6) should be used to assess pulse (criteria 1 and 2 below) and ECG should be 
used to assess for AV block and QTcF interval (criteria 3 and 4 below). 
1. The pulse 6 hours post-dose is < 45 bpm  
2. The pulse 6 hours post-dose is at the lowest value post-dose (suggesting that the 
maximum PD effect on the heart may not yet have occurred) 
3. The ECG 6 hours post-dose shows new onset second degree or higher AV block 
4. The ECG 6 hours post-dose shows a prolonged QTcF interval (> 450 msec for males, 
> 470 msec for females) 
Should post-dose symptomatic bradycardia occur, the treating physician should be notified and 
he or she should initiate appropriate management, begin continuous ECG monitoring, and 
continue observation until the symptoms have resolved.  
Should a patient require pharmacologic intervention for symptomatic bradycardia, continuous 
overnight ECG monitoring in a medical facility should be instituted, and the first dose 
monitoring strategy should be repeated the following day (Day 2).  The first dose monitoring 
strategy should also be repeated at the times specified in Table 2 at Day 5 or Day 8 if any cardiac 
safety issues were observed on the previous Day of dose escalation (see Table 2). 
Patients should have written instruction on when to return to the clinic and a 24-hour contact 
phone number to call in the event of any new or warranted symptoms (eg, chest pain, dizziness, 
palpitations, syncope, nausea, vomiting).  Patients should be instructed not to drive on the same 
day after the first dose of investigational drug administration. 
12.1.10. 
Clinical Laboratory Evaluations 
The central laboratory will analyze the samples.  Further details of the procedures to be followed 
for sample collection, storage, and shipment will be documented in a laboratory manual. 
Additional and repeat laboratory safety testing may be performed at the discretion of the 
Investigator.  

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 Hematology - RBC count, total and differential WBC count (basophils, eosinophils, 
lymphocytes, monocytes, and neutrophils), platelet count, mean platelet volume, 
hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, 
and mean corpuscular hemoglobin concentration.  Total WBC and all differential 
WBC counts will be provided to the site in this open-label trial.  
During the treatment period, WBC differential results will be available to the 
Investigator.  Reductions in ALC levels is a known pharmacodynamic effect of 
RPC1063. If any of the following results are observed, the Investigator will be asked 
to repeat the laboratory tests within approximately 7 days: 
 Absolute neutrophil count [ANC] < 1000 cells/µL 
 Absolute lymphocyte count [ALC] < 200 cells/µL 
If the ANC is confirmed below the acceptable limits, the Investigator will be 
requested to closely monitor for risk of serious infection and institute appropriate 
follow-up, at the discretion of the Investigator. 
If the ALC is confirmed below the 200 cells/µL, the Investigator will temporarily 
discontinue investigational drug and then consult with the Medical Monitor. 
Laboratory testing will be repeated weekly until ALC is > 500 cells/µL. 
When ALC has returned to > 500 cells/µL, treatment may be reinitated at 
Investigator’s discretion (Section 9.1.1 for instructions on resuming treatment after 
missing doses).  For patients whose ALC level is confirmed < 200 cells/μL and has 
not reached the acceptable range (ALC > 500 cells/µL) during the study, laboratory 
testing will be repeated at the 90-day Safety Follow-up Visit. 
 Chemistry   
 Full chemistry panel at Screening: sodium, potassium, chloride, calcium, 
magnesium, phosphate, blood urea nitrogen, glucose, albumin, alkaline 
phosphatase, creatinine, SGPT/ALT, SGOT/AST, GGT, amylase, total bilirubin, 
conjugated bilirubin, total cholesterol, triglycerides, HDL and LDL, C-reactive 
protein.  
 All other visits - blood urea nitrogen, albumin, alkaline phosphatase, creatinine, 
ALT, AST, GGT, amylase, total bilirubin, conjugated bilirubin, C-reactive protein 
 Urinalysis - leukocytes, specific gravity, bilirubin, blood, glucose, ketones, pH, 
protein, urobilinogen, urine color and appearance, and nitrate and leukocyte esterase 
 The central laboratory will analyze routine blood samples.  Details regarding 
collection of samples, shipment of samples, reporting of results, laboratory reference 
ranges, and alerting abnormal values will be supplied to the site before site initiation 
in a trial laboratory manual.  The results of the analysis will be made available to each 
site by the central laboratory. 
 Investigators will be asked to comment on those abnormalities on the respective 
laboratory result page, including a notation of the clinical significance of each 

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abnormal finding in the patient’s source documents.  The laboratory sheets will be 
filed with the patient’s source documents.   
 Pregnancy test: serum beta hCG must be performed at Screening in women of 
childbearing potential; urine beta hCG will be performed in women of childbearing 
potential at each scheduled visit. Between scheduled visits up until the 90-day Safety 
Follow-up Visit, monthly home urine pregnancy tests should be performed by the 
patient.  If a urine pregnancy test result is positive, the investigator will instruct the 
patient to suspend further RPC1063 dosing, if applicable, and schedule a follow-up 
appointment as soon as possible.  A serum pregnancy test will be performed for 
confirmation, including after the 90-day Safety Follow-up Visit, if needed. 
12.2. 
Adverse and Serious Adverse Events 
12.2.1. 
Definition of Adverse Events 
An AE is any untoward medical occurrence in a patient or clinical investigation patient 
administered a pharmaceutical product, which that does not necessarily have a causal 
relationship with the investigational treatment.  An AE can therefore be any unfavorable or 
unintended sign, (including an abnormal laboratory finding,), symptom, or disease temporally 
associated with the use of an investigational medicinal product, whether or not considered related 
to the investigational medicinal product (ICH E2A, II.A.1). 
AEs will be monitored throughout the entire trial including the 90-day Safety Follow-up Visit.  
Investigators will ask the patient at each visit if they have experienced any untoward occurrence 
since the last trial visit.  All AEs will be recorded on the eCRFs provided: a description of the 
event, severity, time of occurrence, duration, any action (e.g. treatment and follow up tests) and 
the outcome should be provided along with the Investigator’s assessment of the relationship to 
the investigational drug. 
In cases of surgical or diagnostic procedures, the condition/illness leading to such a procedure is 
considered as the AE rather than the procedure itself. 
An Adverse Drug Reaction (ADR) is defined as all noxious and unintended responses to a 
medicinal product related to any dose (ICH E2A, II.A.2).   
An Unexpected ADR is defined as an adverse reaction, the nature of which is not consistent with 
the applicable product information (ICH E2A, II.A.3). 
Each AE is to be evaluated for duration, severity, seriousness and causal relationship to the 
investigational drug.  The action taken and the outcome must also be recorded. 
12.2.2. 
Definition of Serious Adverse Events 
Definition of Serious Adverse Event (SAE):  An SAE (experience) or reaction is any untoward 
medical occurrence that at any dose (ICH E2A, II.B): 
 Results in death  
 Is life-threatening  

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NOTE:  The term “life-threatening” in the definition of “serious” refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
 Requires inpatient hospitalization or prolongation of existing hospitalization  
 Results in persistent or significant disability/incapacity, or 
 Is a congenital abnormality/birth defect 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above.  These should 
also usually be considered serious. 
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 drug dependency or drug abuse. 
In case of a fatality, the cause of death is considered as the SAE, and the death is considered as 
its OUTCOME. 
12.2.3. 
Assessment of Adverse Event Severity 
The severity of the AE will be characterized as “mild, moderate, or severe” according to the 
following definitions: 
 Mild events are usually transient and do not interfere with the patient’s daily 
activities. 
 Moderate events introduce a low level of inconvenience or concern to the patient and 
may interfere with daily activities. 
 Severe events are incapacitating and interrupt the patient’s usual daily activity. 
12.2.4. 
Assessment of Adverse Event Relationship to Investigational Drug 
The causal relationship between the investigational drug and the AE has to be characterized as 
unrelated, unlikely, possible, probable, or related.  This medical assessment should be made as 
soon as feasible when reporting an SAE. 
The Investigator is requested to assess the relationship of any AEs to treatment using the 
following definitions: 
Unrelated:  those AEs which are clearly and incontrovertibly due to extraneous causes 
(concurrent drugs, environment, etc) and do not meet the criteria for drug relationship listed 
under Unlikely, Possible, Probable, or Related. 
Unlikely:  An AE may be considered unlikely if it includes at least the first two features: 
 It does not follow a reasonable temporal sequence from administration of the drug  
 It could readily have been produced by the patient’s clinical state, environmental or 
toxic factors, or other modes of therapy administered to the patient  

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 It does not follow a known pattern to the suspected drug  
 It does not reappear or worsen when the drug is re-administered  
Possible: An AE may be considered possible if it includes at least the first two features: 
 It follows a reasonable temporal sequence from administration of the drug  
 It could readily have been produced by the patient’s clinical state, environment or 
toxic factors, or other modes of therapy administered to the patient 
 It follows a known response pattern to the suspected drug 
Probable: An AE may be considered probable if it includes at least the first three features: 
 It follows a reasonable temporal sequence from administration of the drug 
 It could not be reasonably explained by the known characteristics of the patient’s 
clinical state, environmental or toxic factors or other modes of therapy administered 
to the patient 
 It disappears or decreased on cessation or reduction in dose.  There are exceptions 
when an AE does not disappear upon discontinuation of the drug (eg, bone marrow 
depression, fixed drug eruptions, tardive dyskinesia, etc) 
 It follows a known pattern of response to the suspected drug 
Related: An AE may be considered related if it includes all of the following features: 
 It follows a reasonable temporal sequence from administration of the drug 
 It could not be reasonably explained by the known characteristics of the patient’s 
clinical state, environmental or toxic factors or other modes of therapy administered 
to the patient 
 It disappears or decreased on cessation or reduction in dose.  There are exceptions 
when an AE does not disappear upon discontinuation of the drug (eg, bone marrow 
depression, fixed drug eruptions, tardive dyskinesia, etc.) 
 It follows a known pattern of response to the suspected drug 
 It reappears or worsens if the drug is re-administered 
All efforts should be made to classify the AE according to the above categories. 
After initiation of investigational drug, all AEs, regardless of relationship to investigational drug, 
will be recorded until the patient completes his or her last trial visit. 
12.2.5. 
Reporting of Serious Adverse Events 
Reporting requirements for SAEs will be managed on behalf of the Sponsor by the CRO.  Full 
details of the procedures to be adopted will be documented in a safety management plan 
approved by responsible parties, in brief: 
The Investigator will report any SAE that occurs to any patient from the time written informed 
consent is signed through the last visit.  All SAEs that occur within 90 days of the last dose of 
treatment with the investigational drug, whether or not considered related to the investigational 

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product, must also be reported.  Any SAE that is ongoing when the patient completes the trial or 
discontinues from the trial will be followed by the Investigator until the event has resolved, 
stabilized, or returned to Baseline status. 
Any AE considered serious by the Investigator or Sub-investigator or that meets serious criteria 
should be reported to the CRO’s Pharmacovigilance group using the designated SAE reporting 
forms and procedures within 24 hours from the time the trial site personnel first learned of the 
event.  
The SAE hotline numbers are as follows: 
 
 
 
The initial report should be promptly followed by detailed, written reports, which will include 
copies of hospital case records, discharge summaries, autopsy reports and other documents when 
requested and applicable.  For unrelated cases, a full detailed case description may negate the 
need for additional hospital case records, discharge summaries etc. 
12.2.6. 
Reporting of Serious Adverse Events to Regulatory Authorities and 
Investigators 
Investigators will be notified by the CRO of all SAEs that require prompt submission to their 
IRB or IEC.  Investigators should provide written documentation of IRB/IEC notification for 
each report to the CRO.  The CRO will ensure that all SAEs are reported to the appropriate 
regulatory authorities.  Reporting of SAEs must comply with ICH E6, 4.11.1. 
12.2.7. 
Adverse Events of Special Interest 
Adverse events (AEs) of special interest include bradycardia, heart conduction abnormalities 
(2nd degree and higher AV block), macular edema, malignancy, serious or opportunistic 
infection, pulmonary effects, and hepatic effects. 
Special considerations regarding monitoring for these events are as follows: 
 Bradycardia and heart conduction abnormalities (eg, symptomatic bradycardia, 
2nd degree AV block, QT prolongation): 
- Patients will be closely monitored in the clinic after their first dose of the initial 
dose escalation regimen for a period of 6 hours after treatment.  
Electrocardiograms will occur pre-dose and at Hour 6 following dosing, with 
more frequent assessments if clinically indicated.  Resting pulse and blood 
pressure in the sitting position will be assessed pre-dose and then hourly for 6 
hours following dosing.  See the monitoring guidelines in Section 12.1.9 for 
further details.  
- Investigators should be particularly mindful of patients who have a pulse rate 
< 55 bpm prior to administration of the investigational drug.  Dose should be 
withheld for patients who have a pulse rate of <55 bpm prior to administration of 
investigational drug.  Atropine IV is recommended as the first line treatment of 

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bradycardia, up to a maximum daily dose of 3 mg.  In general, the common 
guidelines for treatment of bradycardia (eg, Advanced Cardiac Life Support 
guidelines) should be followed as appropriate. 
- Patients should be discontinued from participation in the trial if any of the below 
are present: 
o Mobitz type II 2nd degree AV block or  
o 3rd degree AV block or  
o Symptomatic bradycardia that is non-responsive to intervention (e.g., 
atropine or isoproterenol) and lasting ≥ 24 hours (i.e., across the entire 
dosing interval) 
 Pulmonary effects 
 Any condition that might affect the outcome of pulmonary function testing 
including infection, respiratory symptoms, occupational exposures (including 
asbestos) and cigarette smoking needs to be collected before PFT testing and 
transcribed to the pulmonary function tests eCRF page. If patients have decline 
in PFT values (FEV1 and/or FVC) below 50% of the predicted values, treatment 
should be discontinued.  If a patient discontinues due to respiratory AE, the 
Investigator should ensure that the patient has adequate evaluations as clinically 
indicated by a pulmonologist (consider PFTs, chest X-ray or high resolution 
computed tomography, based on findings of the other exams) at the time of the 
AE.  For patients with pulmonary nodules, lung biopsy should be considered 
(Cryptococcus pneumonia and pulmonary TB have been reported with 
fingolimod).  Further evaluations will be conducted until such time as resolution 
is confirmed or no further improvement is expected by the Investigator (based on 
a follow-up period of not less than 3 months). 
 Hepatic effects  
 If patients have elevations in the LFTs (ALT or/and AST) ≥3x ULN, a retest 
should be performed as soon as possible but not later than 14 days after the 
original test.  If the abnormality is confirmed, weekly testing should continue until 
ALT and AST are < 3x ULN.  If the ALT and/or AST stabilizes at a level > 3x 
ULN, the Medical Monitor may agree to less frequent testing.   The Investigator 
should establish causality.   
 At any time, if any of the following occur and there are no apparent alternative 
causes for the finding, the investigational drug must be permanently discontinued 
: 
o ALT or AST > 8x ULN or 
o ALT or AST > 5x ULN with confirmation, within 2 weeks or 
o ALT or AST > 3x ULN and (total bilirubin > 2x ULN or INR > 1.5) or 

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o ALT or AST > 3x ULN with the appearance of fatigue, nausea, vomiting, 
or right upper quadrant pain or tenderness, fever, rash and/or eosinophilia 
(>5%) 
Investigator should establish causality. 
After discontinuation due to elevation of ALT or AST > 5x ULN or concurrent 
elevations of ALT or AST > 3x ULN and bilirubin > 2x ULN, further liver 
function evaluation should be performed (for example, coagulation panel and 
alkaline phosphatase) in consultation with the Medical Monitor. 
 Evaluation of alternative causes for the liver test abnormalities could include any 
of the following: 
o Acute viral hepatitis 
o Alcoholic or autoimmune hepatitis 
o Hepatobiliary disorders 
o NASH 
o Cardiovascular causes 
o Concomitant treatments 
 Macular edema 
 For patients with abnormal OCT findings or with visual signs or symptoms of 
new onset or worsening macular edema that develop following initiation of 
treatment, a general ophthalmologic examination including eye history, visual 
acuity, and dilated ophthalmoscopy will also be performed 
 Investigational drug must be discontinued in any patient who has a confirmed 
diagnosis of clinically significant macular edema that is of new onset or worsened 
since baseline 
 Patients with a diagnosis of macular edema must be followed up monthly and 
more frequently if needed based on the ophthalmologist's judgment 
 Malignancies  
 Because RPC1063 is an immunomodulator, patients should be carefully 
monitored for infections and malignancies (including dermatologic malignancy) 
 The treating Investigator will complete a dermatological examination for 
monitoring of the potential development of new cutaneous malignancies during 
the trial.  Patients with any suspicious finding noted during the examination will 
be referred to an appropriately qualified dermatologist for evaluation and 
treatment, if warranted 
 Serious or opportunistic infections  
- TB, serious bacterial infections, systemic fungal infections, viral infections such 
as herpes infections (including herpes zoster and disseminated herpes simplex) 
and protozoan infections should be reported as AEs  

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- During the treatment period if a serious infection or a serious opportunistic 
infection is identified, investigational drug should be suspended until the patient 
has received appropriate treatment and has had resolution of the infection.  
Investigational drug can be restarted at the Investigator’s discretion after 
assessment of the patient’s clinical status (See Section 9.1.1 for instructions on 
resuming treatment after missing doses)  
- Patients withdrawn from the trial as a result of the above will be followed until 
lymphocyte levels return to the patient’s pre-treatment baseline or to the central 
laboratory’s Lower Limit of Normal, whichever is lower 
12.2.8. 
Monitoring of Patients with Adverse Events, Serious Adverse Events, and 
Adverse Events of Special Interest 
Investigators must carefully monitor each patient for AEs.  This includes clinical laboratory 
variables.  Assessments must be made of the seriousness, severity, and relationship to the 
administration of the investigational drug.  After the initial AE/SAE report, the Investigator is 
required to follow up proactively with each patient and provide further information to the CRO 
on the patient’s condition.  During the trial, all AE/SAEs should be followed up to resolution 
unless the event is considered by the Investigator to be unlikely to resolve due to the patient’s 
underlying disease, or the patient is lost to follow-up.  Safety reporting must comply with 
ICH E6, 4.11. 
12.2.9. 
Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB) for the trial will at a minimum perform 
quarterly safety reviews starting after the first patient is dosed. 
12.2.10. 
Treatment of Overdose of Investigational Drug 
An overdose is any dose of investigational drug given to a patient or taken by a patient that 
exceeds the dose described in the protocol.  There is no information regarding overdose with 
RPC1063.  Any overdose, with or without associated AEs, must be promptly reported to the 
CRO’s Medical Monitor or other designated Drug Safety Center.  Overdoses do not need to be 
recorded as AEs in the eCRF; only in the case of any AEs associated with the overdose should 
these be reported on relevant AE/SAE sections in the eCRF.  
12.2.11. 
Procedures in Case of Pregnancy 
If a urine pregnancy test is positive, the Investigator will instruct the patient to suspend further 
RPC1063 dosing. If the test was performed by the patient between scheduled visits, a follow-up 
appointment will be scheduled as soon as possible. A serum pregnancy test will be performed for 
confirmation. 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that an investigational 
product may have interfered with the effectiveness of a contraceptive medication; however, the 
outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or 
congenital abnormality) must be followed up and documented even if the patient was 
discontinued from the trial. 

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Male patients should also be instructed to notify the Investigator in the event that their female 
partner becomes pregnant.  Attempts should be made to follow female partners of trial patients, 
if they should become pregnant.  The Investigator must obtain informed consent from the 
pregnant partner of a trial patient prior to collecting data on her pregnancy and its outcome. 
All reports of congenital abnormalities/birth defects are SAEs.  Spontaneous miscarriages should 
also be reported and handled as SAEs.  Elective abortions without complications should not be 
handled as AEs.  All outcomes of pregnancy must be reported to the Sponsor and/or its designee.  
In cases of live birth, the infant will be followed for up to a year. 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 

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13. 
PLANNED STATISTICAL METHODS 
13.1. 
Determination of Sample Size 
Induction: 
The sample size of 60 patients has been chosen to enable estimates of response and remission 
rates with reasonable precision.  Assuming a remission rate of 15% and a response rate of 30%, 
it is estimated that the confidence interval (half-widths of the 95% CI) around the proportion of 
patients in response and remission will be 12.8% and 16.4% for 30 patients and 9.0% and 11.6% 
for 60 patients. 
13.2. 
Statistical Methods 
13.2.1. 
General Considerations 
All efficacy and safety data will be listed by patient and summarized.  Baseline is defined as the 
last observed measurement prior to the Induction Period Day 1 receipt of investigational drug. 
In general, descriptive summaries will be presented for the efficacy and safety variables 
collected.  Continuous variables will be summarized using number of patients (n), mean, 
standard deviation (SD), median, minimum, and maximum.  Categorical variables will be 
summarized using frequency counts and percentages. 
There will be no imputation for missing efficacy or safety observations 
13.2.2. 
Analysis Populations 
All patient populations will be defined and documented prior to database lock.  Due to the 
open-label, non-randomized nature of the trial design, the intent-to-treat (ITT) and safety 
populations will be the same: all enrolled patients who receive at least one dose of RPC1063.  
These populations will be used as the primary populations for all efficacy and safety parameters. 
13.3. 
Disposition, Demographics and Baseline Characteristics 
The number and percentage of patients in each population will be summarized.  Patient 
disposition, including the number of patients enrolled, dosed, completing the Induction Period, 
and not completing the Induction Period by reason for dropout, entering the Extension Period, 
completing the Extension Period, and not completing the Extension Period by reason for dropout 
will be summarized.  Patient demographics will be summarized and will include age, sex, race, 
ethnicity, height, weight, and body mass index. 
Baseline characteristics will be summarized for and will include age at CD symptom onset, age 
at CD diagnosis, years since CD symptom onset, years since CD diagnosis, baseline CDAI score, 
baseline SES-CD score, baseline PRO2 score, prior anti-TNF use, and prior corticosteroid use. 
Compliance with investigational drug will be summarized and will include the number of 
patients estimated to be < 80% compliant, 80 to 100% compliant, and > 100% compliant.  The 
total dose and average daily dose will also be summarized. 
 

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13.4. 
Induction and Extension Efficacy 
As there are no hypothesis tests on the data collected in this trial, all efficacy endpoints will be 
reported using descriptive statistics.  Proportions of patients in response and proportions of 
patients in remission will include 95% confidence intervals. 
13.5. 
Safety Analyses 
Adverse events will be monitored during the trial and the data analyzed with respect to incidence 
as well as severity and potential relationship of the AEs to investigational drug.  Adverse events 
with onset on, or after the first dose of investigational drug or with onset prior to the first dose of 
investigational drug that increase in severity on, or after the first dose of investigational drug will 
be considered treatment-emergent.  All treatment-emergent AEs will be coded and tabulated by 
system organ class and preferred term.  Incidence of AEs, SAEs, AEs of special interest, and 
AEs leading to discontinuation will be summarized and presented in descending order of 
frequency.  
Associated laboratory parameters such as hepatic enzymes, renal function, and hematology 
values will be grouped and presented together.  Individual patient values will be listed and values 
outside of the standard reference range will be flagged.  Shift tables and analyses of changes 
from baseline will be produced.  The change from baseline for each of the vital signs and ECG 
parameters will be summarized.  Incidence of abnormal vital signs parameters and outlier ECG 
results will be tabulated. 
13.6. 
Pharmacokinetic Analyses 
 
 
 
13.7. 
Interim Analyses 
No formal interim analysis is planned. 

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14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
14.1. 
Monitoring 
The Sponsor has engaged the services of a CRO to perform all monitoring functions within this 
clinical trial.  CRO Clinical Monitors will work in accordance with CRO SOPs and have the 
same rights and responsibilities as monitors from the Sponsor organization.  Clinical Monitors 
will establish and maintain regular contact with the Investigator. 
Monitoring visits will be conducted according to all applicable regulatory requirements and 
standards.  Regular monitoring visits will be made to each center while patients are enrolled 
in the trial.   
14.2. 
Data Management/Coding 
Electronic Data Capture (EDC) will be used for this trial, meaning that all eCRF data will be 
entered in electronic forms at the site.  All EDC systems used in the trial will have access-
controlled security and an audit history available to document any changes made to the data 
throughout the course of the trial.  Data collection recorded in site source documents will be 
entered into the eCRF by authorized site staff designated by the Investigator.  Patients will record 
daily diary information directly into an electronic diary, and this will be considered a source 
document.  Appropriate training and security measures will be completed with the Investigator, 
all authorized site staff, and patients prior to the trial being initiated and any data being entered 
into the system for and/or by any trial patients. 
All data entered by the site staff must be entered in English.  The eCRFs should be completed 
contemporaneous to the patient’s visit.  The Investigator may delegate data entry, but is 
responsible for verifying that all data entries in the eCRFs are accurate and correct at the 
conclusion of the trial.   
Source documents are all documents used by the Investigator or hospital that relate to the 
patient’s medical history, that verify the existence of the patient, the inclusion and exclusion 
criteria, and all records covering the patient’s participation in the trial.  They include laboratory 
notes, ECG results, memoranda, pharmacy dispensing records, patient files, etc. 
Source documents will be made available for inspection by the Clinical Monitor at each 
monitoring visit.  The Investigator must complete eCRFs for each patient who receives 
investigational drug.  Any copy of source document(s) that are provided to the Sponsor or its 
representatives for any purpose (eg, in support of an SAE report) must be redacted such that all 
patient-identifying information is removed, and clearly labeled with the trial and patient number. 
All AEs and medical histories recorded in the eCRF will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA).  Concomitant medications will be coded using the World 
Health Organization (WHO) drug dictionary.  Versions of dictionaries to be used will be 
specified in the data management plan for the trial. 

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14.3. 
Quality Assurance and Inspections 
Sites, the trial database, and trial documentation may be subject to Quality Assurance audit 
during the course of the trial by the Sponsor or CRO on behalf of the Sponsor.  In addition, 
inspections may be conducted by regulatory bodies at their discretion. 

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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
15.1. 
Study Monitor and Source Data Verification 
According to the Guidelines of Good Clinical Practice (CPMP/ICH/135/95), the Sponsor is 
responsible for implementing and maintaining quality assurance and quality control systems with 
written Standard Operating Procedures (SOPs).   
Quality control will be applied to each stage of data handling.   
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data: 
 Investigator meeting(s)  
 Central laboratories for clinical laboratory parameters and ECGs  
 Center Initiation visit  
 Early center visits post-enrollment  
 Routine center monitoring  
 Ongoing center communication and training  
 Data management quality control checks  
 Continuous data acquisition and cleaning  
 Internal review of data 
 Quality control check of the final clinical study report 
In addition, Sponsor and/or CRO Clinical Quality Assurance Department may conduct periodic 
audits of the trial processes, including, but not limited to trial center, center visits, central 
laboratories, vendors, clinical database, and final clinical study report.  When audits are 
conducted, access must be authorized for all trial-related documents including medical history 
and concomitant medication documentation to authorized Sponsor’s representatives and 
regulatory authorities. 
15.2. 
Product Quality Complaint 
A Product Quality Complaint (PQC) is any written, electronic, or oral communication that 
alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, 
purity, or performance of any drug product manufactured by or on behalf of Celgene after it is 
released for distribution.  PQCs may reduce the usability of the product for its intended function 
or affect performance of the product and therefore pose a significant risk to the patient. Examples 
of PQCs include (but are not limited to): mixed product, mislabeling, lack of effect, 
seal/packaging breach, product missing/short/overage, contamination, suspected falsified, 
tampered, diverted or stolen material, and general product/packaging damage.  If you become 
aware of a suspected PQC, you are obligated to report the issue immediately.  You can do so by 

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emailing customercomplaints@celgene.com or by contacting the Celgene Customer Care Center 
(1-888-423-5436). 

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16. 
ETHICS 
16.1. 
Institutional Review Board or Independent Ethics Committee 
An Independent Ethics Committee should approve the final protocol, including the final version 
of the ICF and any other written information and/or materials to be provided to the patients.  The 
Investigator will provide the Sponsor or CRO with documentation of IRB/IEC approval of the 
protocol and informed consent before the trial may begin at the trial center(s).  The Investigator 
should submit the written approval to the Sponsor or representative before enrollment of any 
patient into the trial. 
The Sponsor or representative should approve any modifications to the ICF that are needed to 
meet local requirements. 
The Investigator will supply documentation to the Sponsor or CRO of required IRB/IEC’s 
annual renewal of the protocol, and any approvals of revisions to the informed consent document 
or amendments to the protocol. 
The Investigator will report promptly to the IRB/IEC, any new information that may adversely 
affect the safety of patients or the conduct of the trial.  Similarly, the Investigator will submit 
written summaries of the trial status to the IRB/IEC annually, or more frequently if requested by 
the IRB/IEC.  Upon completion of the trial, the Investigator will provide the Ethics Committee 
with a brief report of the outcome of the trial, if required. 
16.2. 
Ethical Conduct of the Trial 
This trial will be conducted and the informed consent will be obtained according to the ethical 
principles stated in the Declaration of Helsinki (48th General Assembly, Somerset West, 
Republic of South Africa, October 2008 [or current version]), the applicable guidelines for Good 
Clinical Practice (GCP; CPMP/ICH/135/95), or the applicable drug and data protection laws and 
regulations of the countries where the trial will be conducted. 
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording and reporting trials that involve the participation of human patients.  The 
trial will be conducted in compliance with GCP and the applicable national regulations so as to 
assure that the rights, safety and well-being of the participating trial patients are protected 
consistent with the ethical principles that have their origin in the Declaration of Helsinki. 
16.3. 
Patient Information and Consent 
The Investigator will explain the benefits and risks of participation in the trial to each patient, the 
impartial witness and obtain written informed consent.  Written informed consent must be 
obtained prior to the patient entering the trial and before initiation of any trial related procedure.  
The final, version dated form must be agreed to by the IRB/IEC and must be provided in 
language readily understood by the patient.  In case the patient is unable to read or write, an 
impartial witness should be present during the entire informed consent discussion.  After the 
patient has orally consented to participation in the trial, the witness’ signature on the form will 
attest that the information in the consent form was accurately explained and understood.  The 
Investigator will retain an original consent form for each patient, signed and dated by the patient 
or witness, and by the person who conducted the informed consent discussion.  The Investigator 

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will supply all enrolled patients with either a copy of their signed informed consent or, 
depending upon local requirements, a second original informed consent, signed by both parties. 
The consent form may need to be revised during the trial due to a protocol amendment or should 
important new information become available that may be relevant to the safety of the patient.  In 
this instance, approval should always be given by the IRB/IEC and existing patients informed of 
the changes and re-consented, as directed by the IRB/IEC and in accordance with its policies and 
procedures; however, in some instances where an immediate change is necessary to eliminate an 
apparent hazard to patients, then it would not be necessary for a protocol amendment to receive 
IRB/IEC review and approval before being implemented.  Those patients who are presently 
enrolled and actively participating in the trial should be informed of the change if it might relate 
to the patients’ willingness to continue their participation in the trial.  
With the consent of the patient, the Investigator should inform the patient’s primary physician 
about participation in the clinical trial. 
16.4. 
Patient Data Protection 
The ICF will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy legislation. 
16.5. 
Investigator Obligations 
This trial will be conducted in accordance with the ICH Harmonized Tripartite Guideline for 
GCP (GCP, 1997); the US Code of Federal Regulations (CFR) Title 21 parts 50, 56, and 312; 
and European Legislation; and the ethical principles that have their origin in the Declaration of 
Helsinki.   
The Investigator agrees to conduct the clinical trial in compliance with this protocol after the 
approval of the protocol by the IEC/IRB in compliance with local regulatory requirements.  
The Investigator and the Sponsor will sign the protocol to confirm this agreement. 
16.6. 
Protocol Signatures 
After reading the protocol, each Investigator will sign the protocol signature page and send a 
copy of the signed page to the Sponsor or representative (Appendix 1).  By signing the protocol, 
the Investigator confirms in writing that he/she has read, understands and will strictly adhere to 
the trial protocol and will conduct the trial in accordance with ICH Tripartite Guidelines for 
Good Clinical Practice and applicable regulatory requirements.  The trial will not be able to start 
at any center where the Investigator has not signed the protocol. 
 

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17. 
DATA HANDLING AND RECORD KEEPING 
17.1. 
Inspection of Records 
The Investigator will prepare and maintain adequate and accurate source documents to record 
all observations and other pertinent data for each patient enrolled in the trial. 
The Investigator will allow the Sponsor, CRO, and authorized regulatory authorities to have 
direct access to all documents pertaining to the trial, including individual patient medical 
records, as appropriate. 
17.2. 
Retention of Records 
It is the Investigator’s responsibility to maintain essential trial documents (protocol and protocol 
amendments, completed eCRFs, signed ICFs, relevant correspondence, and all other supporting 
documentation).  The trial site should plan on retaining such documents for approximately 
15 years after trial completion.  The trial site should retain such documents until at least 2 years 
after the last approval of a marketing application in an International Conference on 
Harmonisation (ICH) region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years after the formal discontinuation of clinical 
development of the investigational product.  These documents should be retained for a longer 
period if required by the applicable regulatory requirements or the hospital, institution, or private 
practice in which the trial is being conducted.  Patient identification codes (patient names and 
corresponding trial numbers) will be retained for this same period of time.  These documents 
may be transferred to another responsible party, acceptable to Sponsor, who agrees to abide by 
the retention policies.  Written notification of transfer must be submitted to Sponsor.  The 
Investigator must contact Sponsor prior to disposing of any trial records.   
No records should be disposed of without the written approval of the Sponsor. 

Sponsor: Celgene International II Sàrl 
 
 
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18. 
PUBLICATION POLICY, FINANCING, AND INSURANCE  
The data generated by this trial are confidential information of the Sponsor.  The Sponsor will 
make the results of the trial publicly available.  The publication policy, finance, and insurance 
information with respect to the Investigator and trial center will be set forth in the Clinical Trial 
Agreement. 

Sponsor: Celgene International II Sàrl 
 
 
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20. 
APPENDIX: INVESTIGATOR SIGNATURE 
PROTOCOL TITLE: 
A Phase 2, Multi-Center, Open-Label Induction Trial with 
Extension Period to Assess Endoscopic Improvement and Changes in Intestinal and Serum 
Biomarkers in Patients with Moderately to Severely Active Crohn's Disease Receiving Oral 
RPC1063 as Induction Therapy 
PROTOCOL NO: 
RPC01-2201 
This protocol is a confidential communication of Celgene International II Sàrl.  I confirm that I 
have read this protocol, I understand it, and I will work according to this protocol.  I will also 
work consistently with the ethical principles that have their origin in the Declaration of Helsinki 
and that are consistent with good clinical practices and the applicable laws and regulations.  
Acceptance of this document constitutes my agreement that no unpublished information 
contained herein will be published or disclosed without prior written approval from Celgene 
International II Sàrl. 
Instructions to the Investigator:  Please SIGN and DATE this signature page.  PRINT your name, 
title, and the name of the site in which the study will be conducted.   
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator: 
______________________________ 
Date: ________ 
Printed Name:  
 
______________________________ 
Investigator Title:  
 
______________________________ 
 
Name/Address of Site: 
______________________________ 
 
 
 
 
______________________________ 
 
 
 
 
______________________________ 
 
 
 
 
 
 
 
 
 
 

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This document summarizes the changes to Protocol RPC01-2201 from Version 4.0 (dated 29 
May 2018) to Version 5.0 (dated 24 May 2019).  
21. 
OVERVIEW OF KEY CHANGES 
The following bulleted list identifies the key changes to the protocol and provides the rationale 
for each change: 
 New contact information 
 Change to safety follow up from 75 days to 90-day (±10 days) Safety Follow-up Visit 
to ensure adequate collection of adverse events that could be associated with 
investigational drug.  The timing of the visit is based on the estimated time needed to 
clear the major active metabolites of RPC1063 in the vast majority of patients (ie, 5 
half-lives of CC112273 and CC1084037 and accounting for variation of half-life 
duration in a human population). 
 Extended requirements for contraception in females after treatment discontinuation 
from the 75-day Safety Follow-up Visit to the 90-day Safety Follow-up Visit. 
 Updated description of RPC1063 to include major active metabolite 
CC1084037compound background 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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22. 
DETAILS OF CHANGES FROM THE PRIOR PROTOCOL 
VERSION 
For each change to the protocol text, Table 9 provides the location of the change, the original 
text, the revised text, and the rationale for the change. Minor editorial changes are not identified. 
Table 9: 
Specific Changes to Protocol RPC01-2201 from Version 4.0 (29 May 2018) to 
Version 5.0 (24 May 2019) 
Protocol 
Section(s) 
Original Text 
Revised Text or New Text 
Rationale 
Protocol 
Synopsis, 
Section 7, 
Table 2, 
Section 8, 
Section 9, 
Section 12,  
75-day Safety Follow-up Visit 
90-day Safety Follow-up Visit 
Title Page  
 
 
  
 
 
 
 
  
 
 
 
Signature 
Page 
 
 
  
 
 
 
 

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Protocol 
Section(s) 
Original Text 
Revised Text or New Text 
Rationale 
Section 5.2 
RPC1063 
RPC1063 is a small molecule 
compound that selectively and 
potently activates the sphingosine 1-
phosphate 1 receptor (S1P1) and S1P5 
receptor (S1P5), although it is more 
selective towards S1P1 over S1P5.  In 
vitro, RPC1063 has little activity on 
the other S1P receptors, showing half 
maximal effective concentration 
(EC50) > 10,000 nM for S1P2, > 5000 
nM for S1P3, and > 2000 nM for S1P4.  
RPC1063 is extensively metabolized 
in humans with up to 13 metabolites 
identified in plasma, urine, and feces, 
including 1 major active metabolite 
(CC112273) in plasma. The RPC1063 
metabolites, CC112273, RP101988, 
RP101075, and RP101442, show a 
similar potency and selectivity profile 
to RPC1063. 
RPC1063( ozanimod) is a sphingosine 
1-phosphate receptor modulator, 
which binds with high affinity 
selectively to sphingosine 1-phosphate 
receptor subtypes 1 and 5. RPC1063 
causes lymphocyte retention in 
lymphoid tissues. The mechanism by 
which RPC1063 exerts therapeutic 
effects in CD (Crohn’s disease) is 
unknown but may involve the 
reduction of lymphocyte migration 
into the central nervous system. 
 
RPC1063 is 10-fold more selective for 
S1P1 relative to S1P5 and has little 
activity on other S1P receptors (S1P2, 
S1P3, and S1P4). RPC1063 is 
extensively metabolized in humans to 
form a number of circulating active 
metabolites. In vitro, RPC1063 and its 
active metabolites demonstrated 
similar activity and selectivity for 
S1P1 and S1P5. In humans, 
approximately 94% of circulating total 
active drug exposure is represented by 
RPC1063 (6%), CC112273 (73%), 
and CC1084037 (15%). 
 
 
 
 
 
 
 
Protocol 
Synopsis, 
Table 2, 
Section 8.1 
 
Counseling about pregnancy 
precautions and the potential risks of 
fetal exposure must be conducted for 
female subjects of childbearing 
potential. The Investigator will 
educate all FCBP about the different 
options of contraceptive methods or 
abstinence as appropriate. The subject 
will be re-educated every time her 
contraceptive measures/methods or 
ability to become pregnant changes. 
The female subject’s chosen form of 
contraception must be effective by the 
time the female subject is randomized 
into the study (for example, hormonal 
contraception should be initiated at 
least 28 days before randomization). 
 
 
 
 
 

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Protocol 
Section(s) 
Original Text 
Revised Text or New Text 
Rationale 
Protocol 
Synopsis, 
Section 8.1 
Male patients: 
Must agree to use a latex condom 
during sexual contact with women of 
childbearing potential while 
participating in the study until 
completion of the 75-day Safety 
Follow-up Visit. 
Removed text 
 
 
 
  
Protocol 
Synopsis, 
Section 8.1 
Acceptable methods of birth control in 
the trial are the following: 
•combined hormonal (oestrogen and 
progestogen containing) contraception, 
which may be oral, intravaginal, or 
transdermal  
•progestogen-only hormonal 
contraception associated with 
inhibition of ovulation, which may be 
oral, injectable, or implantable 
•placement of an intrauterine device 
(IUD) 
•placement of an intrauterine 
hormone-releasing system (IUS) 
•bilateral tubal occlusion 
•vasectomised partner 
•sexual abstinence 
Acceptable methods of birth control in 
the trial are the following: 
•combined hormonal (oestrogen and 
progestogen containing) contraception, 
which may be oral, intravaginal, or 
transdermal  
•progestogen-only hormonal 
contraception associated with 
inhibition of ovulation, which may be 
oral, injectable, or implantable 
•placement of an intrauterine device 
(IUD) 
•placement of an intrauterine 
hormone-releasing system (IUS) 
•bilateral tubal occlusion 
•vasectomised partner 
•complete sexual abstinence