Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis (UC)

A Phase 2, Randomized, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Apremilast (CC-10004) for Treatment of Subjects With Active Ulcerative Colitis

The purpose of the study is to evaluate the clinical efficacy, safety and tolerability of apremilast (30 mg twice daily [BID] and 40 mg BID), compared with placebo, in participants with active Ulcerative Colitis (UC).

Study Overview

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

Detailed Description

Approximately 165 participants (55 subjects per arm) will be randomized in a 1:1:1 ratio to receive oral apremilast (30 mg BID or 40 mg BID), or identically appearing placebo BID for up to 12 weeks, followed by 40 weeks of blinded treatment with apremilast (30 mg BID or 40 mg BID).

At the end of the Blinded Active-treatment Phase (Week 52), participants who have a Mayo endoscopy score ≤ 1 will have the opportunity to participate in the Extension Phase. Participants enrolled in the Extension Phase will receive apremilast for an additional 52 weeks (Weeks 52 to 104). With the implementation of Amendment 4, participants entering the Extension Phase will receive apremilast 30 mg BID. Subjects currently in the Extension Phase who are receiving apremilast 40 mg BID will be switched to 30 mg BID at the next scheduled visit.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Adult Hospital
  • Victoria
    • Footscray, Victoria, Australia, 3011
      • Footscray Hospital
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Multiprofile Hospital for Active Treatment Kaspela
  • Sofia, Bulgaria, 1303
    • Medical Center Asklepion - Humane Medicine Research EOOD
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
  • 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, 1784
    • Clinic of Gastroenterology
  • Varna, Bulgaria, 9010
    • Multiprofile Hospital for Active Treatment Sveta Marina EAD
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Winnipeg Regional Health Authority - Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences Corporation, McMaster University Medical Centre
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv Anny v Brne
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Hradec Králové, Czechia, 500 12
    • Hepato-Gastroenterologie HK, s. r. o.
  • Slany, Czechia, 274 01
    • Nemocnice Slany
• France
  • Amiens, France, 80054
    • Amiens University Hospital
  • Clichy, France, 92110
    • Hopital Beaujon
  • Nantes, France, 602 00
    • CHRU Nantes
  • Nice, France, 06202
    • CHU de Nice Archet I
  • Pierre Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Saint Priest en Jarez, France, 42055
    • Centre Hospitalier Universitaire de Saint Etienne
  • Vandoeuvre les Nancy, France, 54511
    • CHRU Nancy
• Germany
  • Berlin, Germany, 14050
    • DRK Kliniken Berlin Westend
  • Frankfurt, Germany, 60594
    • Crohn-Colitis-Centre Rhein-Main
  • Keil, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein
  • Minden, Germany, 32423
    • Gastroenterologische Praxis Minden
• Hungary
  • Budapest, Hungary, 1139
    • ENDOMEDIX Kft.
  • Budapest, Hungary, 1136
    • Pannonia Maganorvosi Centrum Kft.
  • Debrecen, Hungary, 4025
    • Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja
  • Mosonmagyaróvár, Hungary, 9200
    • Karolina Korhaz Rendelointezet
  • Szeged, Hungary, 6720
    • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
  • Szekszárd, Hungary, 7100
    • Tolna Megyei Balassa Janos Korhaz
  • Vác, Hungary, 2600
    • Javorszky Odon Korhaz
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi
  • Milan, Italy, 20089
    • IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
  • Roma, Italy, 00168
    • Complesso Integrato Columbus
  • Roma, Italy, 00133
    • Fondazione PTV Policlinico Tor Vergata
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Rotterdam, Netherlands, 3083 AN
    • Ikazia Ziekenhuis
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Dunedin, New Zealand, 9016
    • Dunedin Hospital
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Bydgoszcz, Poland, 85-794
    • Osrodek Badan Klinicznych CLINSANTE S.C.
  • Czestochowa, Poland, 42 202
    • Centrum Medyczne sw. Lukasza
  • Katowice, Poland, 40 659
    • Economicus - NZOZ ALL-MEDICUS
  • Sopot, Poland, 81-756
    • ENDOSKOPIA Sp. z o.o.
  • Szczecin, Poland, 71-685
    • Sonomed Sp. z o.o.
  • Torun, Poland, 40 659
    • Gastromed Kopon Zmudzinski i Wspolnicy Sp. j. Specjalistyczne Centrum Gastrologii i Endoskopii Spec. Gabinety Lekarskie
  • Warsaw, Poland, 00-632
    • Centrum Zdrowia Matki, Dziecka i Mlodziezy
  • Warszawa, Poland, 03-563
    • Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
  • Wroclaw, Poland, 03-580
    • Lexmedica Drubajlo Hanna
  • Wroclaw, Poland, 53-333
    • ARS Médica
• Russian Federation
  • Kazan, Russian Federation, 420064
    • Republican Clinical Hospital
  • Moscow, Russian Federation, 115088
    • Stolitsa-Medikl, LLC
  • Rostov on Don, Russian Federation, 344022
    • SEIHPE Rostov State Medical University of MoH of RF
  • Saratov, Russian Federation, 410053
    • Regional Clinical Hospital
  • St Petersburg, Russian Federation, 129329
    • Russian Medical Military Academy na SMKirov
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Central City Clinical Hospital
  • Ivano-Frankivsk, Ukraine, 58001
    • Regional Clinical Hospital, Gastroenterology department, State Higher Education Institute Ivano-Frankivsk National Medical University
  • Ivano-Frankivsk, Ukraine, 76008
    • Ivano-Frankivsk Regional Clinical Hospital
  • Kharkiv, Ukraine, 61037
    • Kharkiv City Clinical Hospital 2
  • Kirovograd, Ukraine, 25006
    • Private Enterprise Private Manufacture Company Acinus
  • Kremenchuk, Ukraine, 39617
    • Kremenchuk City Hospital # 1 n.a O.T.Bohaievskyi
  • Lviv, Ukraine, 79059
    • Lviv Emergency Clinical Hospital, Therapeutics Department No. 1
  • Odesa, Ukraine, 65025
    • Municipal Institution Odesa Regional Clinical Hospital
  • Uzhgorod, Ukraine, 88000
    • Central City Clinical Hospital
  • Vinnytsia, Ukraine, 21018
    • Vinnytsia Regional Clinical Hospital n a M I Pyrohov
  • Zaporizhzhia, Ukraine, 69600
    • Municipal Institution Zaporizhzhia
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists of the Southeast
  • California
    • Los Angeles, California, United States, 90045
      • Southern California Research Institute Medical Group, Inc.
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Connecticut Clinical Research Foundation
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Consultants for Clinical Research of South Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Lauderdale Lakes, Florida, United States, 33319
      • Precision Clinical Research, LLC
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic, Inc.
    • Naples, Florida, United States, 34102
      • Gastroenterology Group Of Naples
    • Port Orange, Florida, United States, 32127
      • Advanced Medical Research Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMASS Medical Center
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health Research
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Gastrointestinal Associates PA
  • New York
    • Great Neck, New York, United States, 11021
      • NYU Langone Long Island Clinical Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research
  • Tennessee
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research
  • Texas
    • Live Oak, Texas, United States, 78233
      • Digestive Research Center/ Gastroenterology Consultants of San Antonio
    • Pasadena, Texas, United States, 77505
      • Digestive Health Specialist of Tyler
    • San Antonio, Texas, United States, 78229
      • San Antonio Gastroenterology
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

• Male or female aged 18 and over at the time of signing the informed consent.
• Must understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
• Diagnosis of ulcerative colitis (UC) with a duration of at least 3 months prior to the Screening Visit..
• Total Mayo Score (TMS) ≥ 6 to ≤ 11 (range: 0-12) at baseline, prior to randomization in the study.
• Endoscopic subscore ≥ 2 (range: 0-3) on the Mayo score prior to randomization in the study.
• Subjects must have had a therapeutic failure, been intolerant to, or have a contraindication to, at least one of the following: oral aminosalicylates (ie, 5-aminosalicylic acid [5-ASA] compounds or sulfasalazine [SSZ]), budesonide, systemic corticosteroids, or immunosuppressants (eg, 6-mercaptopurine [6-MP], azathioprine [AZA], or methotrexate [MTX]).

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

• Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.
• Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis).
• Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study.
• Clinical signs suggestive of fulminant colitis or toxic megacolon.
• Prior use of any tumor necrosing factor (TNF) inhibitor (or any biologic agent).
• Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide.
• Use of intravenous (IV) corticosteroids within 2 weeks of the Screening Visit.
• Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks of the Screening Visit.
• Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit.
• History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would preclude participation in the study.

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: Apremilast 30 mg PO BID; Apremilast 30 mg by mouth (PO) twice a day (BID) for 12 weeks After 12 weeks: Participants who achieve at least a 20% decrease from baseline in the total Mayo score (TMS) will continue to receive apremilast 30 mg BID for an additional 40 weeks. (Wk 52); Participants who do not achieve at least a 20% decrease from baseline in the TMS will receive apremilast 40 mg BID for an additional 40 weeks (Wk 52) After 52 weeks, participants who are eligible for the Extension Phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)	Drug: Apremilast; Other Names: CC-10004; Otezla
Experimental: Apremilast 40 mg PO BID; Apremilast 40 mg by mouth (PO) twice a day (BID) for 12 weeks After 12 weeks, participants assigned to the 40 mg BID dose of apremilast at baseline will continue to receive apremilast 40 mg BID for an additional 40 weeks (Wk 52) After 52 weeks, participants who are eligible for the extension Phase will continue to receive apremilast 40 mg BID for an additional 52 weeks (Wk 104)	Drug: Apremilast; Other Names: CC-10004; Otezla
Placebo Comparator: Placebo BID; Identically matching placebo by mouth (PO) twice a day (BID) for 12 weeks. After 12 weeks all participants randomized to placebo at baseline will be re-randomized to receive apremilast 30 mg or 40 mg BID for an additional 40 weeks (Wk 52) After Wk 52, participants who are eligible for the extension phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)	Drug: Placebo; Drug: Apremilast; Other Names: CC-10004; Otezla

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12	Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease.; Stool Frequency Subscore (SFS); Rectal Bleeding Subscore (RBS); Endoscopy Subscore; Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12	Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease.; Stool Frequency Subscore (SFS); Rectal Bleeding Subscore; Endoscopy Subscore; Physician's Global Assessment (PGA) Rectal bleeding (subscore 0-3) was defined as: 0 = No blood seen; = Streaks of blood with stool less than half the time; = Obvious blood with stool; = Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.	Week 12
Percentage of Participants Who Achieved an Endoscopic Remission at Week 12	An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12. The MES subscore findings were defined as: 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) The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.	Week 12
Percentage of Participants Who Achieved an Endoscopic Response at Week 12	An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as: 0 = Normal or inactive disease; = Mild Disease (erythema, decreased vascular pattern, mild friability); = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration). The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.	Week 12
Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12	The RBS was measured as: 0 = No blood seen; = Streaks of blood with stool less than half the time; = Obvious blood with stool most of the time; = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method.	Week 12
Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12	Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore > 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.	Week 12
Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12	Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was measured as: 0 = No blood seen; = Streaks of blood with stool less than half the time; = Obvious blood with stool most of the time; = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.	Week 12
Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8	Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore >1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.	Week 8
Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8	Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.	Week 8
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase	A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred 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 = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain	From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks
The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period	A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred 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 = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.	From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52	A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred 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 = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain	From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase)	A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred 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 = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain	From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Danese S, Neurath MF, Kopon A, Zakko SF, Simmons TC, Fogel R, Siegel CA, Panaccione R, Zhan X, Usiskin K, Chitkara D. Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2526-2534.e9. doi: 10.1016/j.cgh.2019.12.032. Epub 2020 Jan 8.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2015
• Primary Completion (Actual): September 25, 2017
• Study Completion (Actual): June 3, 2019

Study Registration Dates

• First Submitted: November 10, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 13, 2014

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Inflammatory Bowel Disease
• 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; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: CC-10004-UC-001; 2014-002981-64 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)