Efficacy and Safety Study of Ozanimod in Ulcerative Colitis (Touchstone)

A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo Controlled Parallel-Group Study to Evaluate the Clinical Efficacy and Safety of Induction Therapy With RPC1063 in Patients With Moderately to Severely Active Ulcerative Colitis

The purpose of this study is to determine whether RPC1063 is effective in the treatment of ulcerative colitis (UC).

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Drug: Ozanimod

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven, campus Gasthuisberg
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Multiprofile Hospital for Active Treatment Kaspela
  • Sofia, Bulgaria, 1606
    • Military Medical Academy
  • Sofia, Bulgaria, 1407
    • University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia
  • Sofia, Bulgaria, 1527
    • University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna ISUL EAD
  • Sofia, Bulgaria, 1431
    • UMHAT Sv Ivan Rilski EAD
  • Sofia, Bulgaria, 1632
    • Multiprofile Hospital for Active Treatment Doverie AD
  • Sofia, Bulgaria, 1712
    • Multiprofile Hospital for Active Treatment Sveti Panteleimon - Sofia AD
  • Sofia, Bulgaria, 1797
    • Multiprofile Hospital for Active Treatment Sofiamed
  • Varna, Bulgaria, 9010
    • Multiprofile Hospital for Active Treatment Sveta Marina EAD
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre, University Hospital
• Greece
  • Athens, Greece, 106 76
    • Evaggelismos General Hospital
  • Ioannina, Greece, 45110
    • University Hospital of Ioannina
  • Larissa, Greece, 41110
    • University Hospital Of Larissa
• Hungary
  • Budapest, Hungary, 1062
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Budapest, Hungary, 1136
    • Pannónia Magánorvosi Centrum
  • Budapest, Hungary, 1145
    • Uzsoki Utcai Kórház
  • Debrecen, Hungary, 4025
    • Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center
  • Haifa, Israel, 34362
    • Carmel Medical Center
  • Holon, Israel, 5822012
    • Wolfson Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
• Korea, Republic of
  • Daegu, Korea, Republic of, 705717
    • Yeungnam University Medical Center
  • Daejon, Korea, Republic of, 302718
    • Konyang University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 158-710
    • Ewha Womans University Mokdong Hospital
  • Seoul, Korea, Republic of, 110746
    • Kangbuk Samsung Medical Center
  • Seoul, Korea, Republic of, 130702
    • Kyunghee University Medical Center
  • Suwon, Korea, Republic of, 442723
    • The Catholic University of Korea, St.Vicent's Hospital
  • Wonju, Korea, Republic of, 220701
    • Wonju Christian Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Dordrecht, Netherlands, 3318 AT
    • Albert Schweitzer Ziekenhuis
  • Rotterdam, Netherlands, 3083 AN
    • Ikazia Ziekenhuis
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Dunedin, New Zealand, 9016
    • Dunedin Hospital
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
  • Lower Hutt, New Zealand, 5010
    • Hutt Valley District Health Board
  • Milford, New Zealand, 0620
    • North Shore Hospital
• Poland
  • Bialystok, Poland
    • SPZOZ Wojewodzki Szpital Zespolony im. J.Sniadeckiego
  • Czestochowa, Poland, 42-217
    • Niepubliczny Zaklad Opieki Zdrowotnej Intermed
  • Elblag, Poland, 82-300
    • Elblaski Szpital Specjalistyczny z Przychodnia
  • Gdansk, Poland, 80-807
    • Przychodnia Lekarska Nowy Chelm
  • Katowice, Poland, 40-660
    • Economicus - NZOZ ALL-MEDICUS
  • Ksawerow, Poland, 95-054
    • Centrum Opieki Zdrowotnej Orkan Med
  • Lodz, Poland, 90-302
    • Niepubliczny Zaklad Opieki Zdrowotnej CENTRUM MEDYCZNE Szpital Swietej Rodziny
  • Lublin, Poland, 20-090
    • Instytut Medycyny Wsi
  • Rzeszow, Poland, 35-068
    • MEDICOR Centrum Medyczne
  • Warsaw, Poland, 03-580
    • Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
  • Warszawa, Poland, 02-797
    • Niepubliczny Zaklad Opieki Zdrowotnej Triclinium
  • Wroclaw, Poland, 53-114
    • LexMedica Osrodek Badan Klinicznych
• Russian Federation
  • Krasnoyarsk, Russian Federation, 660022
    • Regional Clinical Hospital
  • Moscow, Russian Federation, 119991
    • SBEI HPE First Moscow State Medical University n.a. I.M. Sechenov of the MoH of the RF
  • Nizhniy Novgorod, Russian Federation, 603126
    • Nizhegorodskaya Regional Clinical Hospital n.a. N.A. Semashko
  • Novosibirsk, Russian Federation, 630084
    • Novosibirsk State Medical University
  • Omsk, Russian Federation, 644043
    • SBEI of HPE Omsk State Medical Academy Ministry of healthcare of RF
  • Rostov on Don, Russian Federation, 344022
    • SEIHPE Rostov State Medical University of MoH of RF
  • Saint Petersburg, Russian Federation, 191163
    • Russian Medical Military Academy na SMKirov
  • Saint Petersburg, Russian Federation, 196247
    • City Hospital 26
  • Samara, Russian Federation, 443000
    • Medical Company Hepatolog
• Slovakia
  • Ilava, Slovakia, 01901
    • Slovak Research Center
  • Nitra, Slovakia, 94901
    • Specializovana Nemocnica Svorada Zobor
  • Presov, Slovakia, 080 01
    • GASTRO I., s.r.o.
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76008
    • Ivano-Frankivsk Regional Clinical Hospital
  • Ivano-Frankivsk, Ukraine, 76014
    • Ivano-Frankivsk City Clinical Hospital #1 Dep of Surgery SHEI Ivano-Frankivsk NMU
  • Kharkiv, Ukraine, 61039
    • Institute of Therapy n.a. L.T. Maloy of NAMS of Ukraine
  • Kyiv, Ukraine, 04201
    • Kyiv CCH #8 Dept of Gastroenterology P.L. Shupyk NMA of PGE
  • Kyiv, Ukraine, 1133
    • Order of the Red Star MMMCC MMCH Clinic of Gastroenterology
  • Kyiv, Ukraine, 2232
    • CNI Consultative and Diagnostic Center of Desnianskyi District of Kyiv
  • Lviv, Ukraine, 79059
    • Communal City Clinical Hospital of Ambulance, Dept of Therapy #1 D.Halytskyi Lviv NMU
  • Lviv, Ukraine, 79010
    • Lviv Regional Clinical Hospital
  • Vinnytsia, Ukraine, 21018
    • Vinnytsia Regional Clinical
  • Vinnytsya, Ukraine, 21029
    • Medical Clinical Research Center "Health Clinic"
  • Zaporizhzhia, Ukraine, 69600
    • Municipal Institution Zaporizhzhia
  • Zaporizhzhya, Ukraine, 69065
    • Zaporizhzhya city multidisciplinary clinical hospital #9
• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • La Jolla, California, United States, 92037
      • University Of California San Diego
    • Oceanside, California, United States, 92056
      • Alliance Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastroenterology Associates, LLC
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Chevy Chase Clinical Research
    • Towson, Maryland, United States, 21204
      • Endoscopic Microsurgery Associates
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
  • New York
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ulcerative colitis (UC) confirmed on endoscopy
• Moderately to severely active UC (Mayo score 6-12)

Exclusion Criteria:

• Current use of anti-TNF agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ozanimod 0.5 mg; Participants received 0.5 mg capsules of ozanimod hydrochloride daily during the induction period weeks 0-9 (an initial 8-day dose escalation regimen in the induction period that consisted of 4 days of ozanimod HCl 0.25 mg (equivalent to ozanimod 0.23 mg), followed by 3 days of ozanimod HCl 0.5 mg, (equivalent to ozanimod 0.46 mg) followed by the assigned treatment level for at least 8 weeks. Participants who completed the induction period and were responders at week 8, continued to receive the same dose of ozanimod during the maintenance period up to week 32. Participants who received ozanimod 0.5 mg capsules and completed the induction period and were non-responders at Week 8 and who completed the maintenance period or experienced a disease relapse, were given the option to enter the OLP and receive 1 mg ozaninod capsules daily up to 6 years. Participants who had not shown clinical improvement 8 weeks after initiation of the OLP were discontinued from the study.	Drug: Ozanimod; Ozanimod capsules by mouth daily.; Other Names: Zeposia, RPC 1063
Experimental: Ozanimod 1 mg; Participants received 1 mg capsules of ozanimod hydrochloride daily during the induction period weeks 0-9 (an initial 8-day dose escalation regimen in the induction period that consisted of 4 days of ozanimod HCl 0.25 mg (equivalent to ozanimod 0.23 mg), followed by 3 days of ozanimod HCl 0.5 mg, (equivalent to ozanimod 0.46 mg) followed by the assigned treatment level for at least 8 weeks. Participants who completed the induction period and were responders at week 8, continued to receive the same dose of ozanimod during the maintenance period up to week 32. Participants who received ozanimod 1 mg capsules and completed the induction period and were non-responders at Week 8 and who completed the maintenance period or experienced a disease relapse, were given the option to enter the OLP and receive 1 mg ozaninod capsules daily up to 6 years. Participants who had not shown clinical improvement 8 weeks after initiation of the OLP were discontinued from the study.	Drug: Ozanimod; Ozanimod capsules by mouth daily.; Other Names: Zeposia, RPC 1063
Placebo Comparator: Placebo; Identically matching placebo capsules daily for 32 weeks followed by an optional open label treatment period.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Clinical Remission Based on the Central Read of the Mayo Score (MS), at Week 8	Clinical Remission was defined as: Mayo score of <2 points and with no individual subscore of > 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease.; Stool Frequency Subscore (SFS); Rectal bleeding Subscore (RBS); Endoscopy Subscore; Physician's Global Assessment (PGA) Clinical Remission was based on the 4-component Mayo definition.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Clinical Response in the Mayo Score (MS) at Week 8	Clinical response was defined as a reduction from baseline in Mayo score ≥3 points and ≥30%, and a decrease from baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. Clinical Respone was based on the 4-component Mayo definition.	Week 8
Change From Baseline in Mayo Score at Week 8	The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease.; Stool Frequency Subscore (SFS); Rectal bleeding Subscore (RBS); Endoscopy Subscore; Physician's Global Assessment (PGA)	Baseline to Week 8
Percentage of Participants With Mucosal Healing at Week 8	Mucosal healing is defined as an endoscopy subscore ≤ 1 point. Endoscopy subscores were calculated based on central endoscopy reading. The endoscopy scale: 0 = Normal or inactive disease; = Mild disease (erythema, decreased vascular pattern, mild friability); = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); = Severe disease (spontaneous bleeding, ulceration)	Week 8
Percentage of Participants Who Achieved Clinical Remission in the Mayo Score at Week 32	Clinical Remission was defined as: Mayo score of <2 points and with no individual subscore of > 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a score of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease.; Stool Frequency Subscore (SFS); Rectal bleeding Subscore (RBS); Endoscopy Subscore; Physician's Global Assessment (PGA)	Week 32
Percentage of Participants Who Achieved Clinical Response at Week 32	Clinical response was defined as a reduction from baseline in Mayo score ≥3 points and ≥30%, and a decrease from baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease.; Stool Frequency Subscore (SFS); Rectal bleeding Subscore (RBS); Endoscopy Subscore; Physician's Global Assessment (PGA)	Week 32
Percentage of Participants With Mucosal Healing at Week 32	Mucosal healing is defined as an endoscopy subscore ≤ 1 point. Endoscopy subscores were calculated based on central endoscopy reading. The endoscopy scale: 0 = Normal or inactive disease; = Mild disease (erythema, decreased vascular pattern, mild friability); = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); = Severe disease (spontaneous bleeding, ulceration)	Week 32
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction Period	A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities.	From the first dose of investigational product (IP) up to 90 days after the last dose of IP or at follow-up visit; the mean total duration of IP exposure was 52.8 days, 56.1 days and 50.8 days respectively for 0.5 mg, 1 mg ozanimod and placebo
Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Maintenance Period	A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities.	From the first dose of IP up to 90 days after the last dose of IP or at follow-up visit; the mean total duration of IP exposure was 156.3 days, 171.1 days and 154.5 days respectively for 0.5 mg, 1 mg ozanimod and placebo.
Number of Participants With TEAE During the Open-Label Treatment Period (OLP)	A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities.	From the first dose of IP until 90 days after the last dose of IP or at follow-up visit; the mean total duration of study drug exposure in the OLP was 2.42 years

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: AnnKatrin Petersen, MD, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Sandborn WJ, Feagan BG, Wolf DC, D'Haens G, Vermeire S, Hanauer SB, Ghosh S, Smith H, Cravets M, Frohna PA, Aranda R, Gujrathi S, Olson A; TOUCHSTONE Study Group. Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis. N Engl J Med. 2016 May 5;374(18):1754-62. doi: 10.1056/NEJMoa1513248.

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2012
• Primary Completion (Actual): March 10, 2015
• Study Completion (Actual): August 30, 2019

Study Registration Dates

• First Submitted: July 19, 2012
• First Submitted That Met QC Criteria: July 19, 2012
• First Posted (Estimate): July 23, 2012

Study Record Updates

• Last Update Posted (Actual): May 19, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Ozanimod
• Other Study ID Numbers: RPC01-202