Ulcerative ColitisPhase 2UCNCT02289417
Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis
A Phase 2 study testing Apremilast in people with Ulcerative Colitis, run by Amgen at 99 sites in 14 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Apremilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 170 participants
- Where
- 99 sitesin 14 countries
- Study dates
- 8 Jan 2015to 3 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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]).
Who cannot join
- 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).
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- 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.
Trial locations and contacts
99 sites in 14 countries.
99 sites in 14 countries
United States25 sites
Consultants for Clinical Research of South Florida
Boynton Beach, Florida, 33426
Connecticut Clinical Research Foundation
Bristol, Connecticut, 06010
Clinical Research Institute of Michigan, LLC
Chesterfield, Michigan, 48047
University of Chicago Medical Center
Chicago, Illinois, 60637
Consultants for Clinical Research
Cincinnati, Ohio, 45219
Avail Clinical Research, LLC
DeLand, Florida, 32720
Digestive Health Specialists of The Southeast
Dothan, Alabama, 36305
Gastrointestinal Associates PA
Flowood, Mississippi, 39232
NYU Langone Long Island Clinical Research Associates
Great Neck, New York, 11021
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Precision Clinical Research, LLC
Lauderdale Lakes, Florida, 33319
Digestive Research Center/ Gastroenterology Consultants of San Antonio
Live Oak, Texas, 78233
Southern California Research Institute Medical Group, Inc.
Los Angeles, California, 90045
University of Louisville
Louisville, Kentucky, 40202
Pharmax Research Clinic, Inc.
Miami, Florida, 33126
Gastroenterology Group of Naples
Naples, Florida, 34102
Quality Medical Research
Nashville, Tennessee, 37211
Digestive Health Specialist of Tyler
Pasadena, Texas, 77505
Advanced Medical Research Center
Port Orange, Florida, 32127
University of Utah
Salt Lake City, Utah, 84132
San Antonio Gastroenterology
San Antonio, Texas, 78229
Harborview Medical Center
Seattle, Washington, 98104
University of Washington Medical Center
Seattle, Washington, 98195
Center for Digestive Health Research
Troy, Michigan, 48098
UMass Medical Center
Worcester, Massachusetts, 01655
Poland11 sites
Uniwersytecki Szpital Kliniczny w Bialymstoku
Bialystok, 15-276
Osrodek Badan Klinicznych CLINSANTE S.C.
Bydgoszcz, 85-794
Centrum Medyczne sw. Lukasza
Częstochowa, 42 202
Economicus - NZOZ ALL-MEDICUS
Katowice, 40 659
Endoskopia Sp. z o.o.
Sopot, 81-756
Sonomed Sp. z o.o.
Szczecin, 71-685
Gastromed Kopon Zmudzinski i Wspolnicy Sp. j. Specjalistyczne Centrum Gastrologii i Endoskopii Spec. Gabinety Lekarskie
Torun, 40 659
Centrum Zdrowia Matki, Dziecka i Mlodziezy
Warsaw, 00-632
Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
Warsaw, 03-563
Lexmedica Drubajlo Hanna
Wroclaw, 03-580
Ars Medica
Wroclaw, 53-333
Ukraine11 sites
Regional Clinical Hospital, Gastroenterology department, State Higher Education Institute Ivano-Frankivsk National Medical University
Ivano-Frankivsk, 58001
Ivano-Frankivsk Regional Clinical Hospital
Ivano-Frankivsk, 76008
Ivano-Frankivsk Central City Clinical Hospital
Ivano-Frankivsk, 76018
Kharkiv City Clinical Hospital 2
Kharkiv, 61037
Private Enterprise Private Manufacture Company Acinus
Kirovograd, 25006
Kremenchuk City Hospital # 1 n.a O.T.Bohaievskyi
Kremenchuk, 39617
Lviv Emergency Clinical Hospital, Therapeutics Department No. 1
Lviv, 79059
Municipal Institution Odesa Regional Clinical Hospital
Odesa, 65025
Central City Clinical Hospital
Uzhhorod, 88000
Vinnytsia Regional Clinical Hospital n a M I Pyrohov
Vinnytsia, 21018
Municipal Institution Zaporizhzhia
Zaporizhzhya, 69600
Bulgaria7 sites
Multiprofile Hospital for Active Treatment Kaspela
Plovdiv, 4002
Medical Center Asklepion - Humane Medicine Research EOOD
Sofia, 1303
University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia
Sofia, 1407
University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
Sofia, 1431
University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna ISUL EAD
Sofia, 1527
Clinic of Gastroenterology
Sofia, 1784
Multiprofile Hospital for Active Treatment Sveta Marina EAD
Varna, 9010
France7 sites
Amiens University Hospital
Amiens, 80054
Hopital Beaujon
Clichy, 92110
CHRU Nantes
Nantes, 602 00
CHU de Nice Archet I
Nice, 06202
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Centre Hospitalier Universitaire de Saint Etienne
Saint-Priest-en-Jarez, 42055
CHRU Nancy
Vandœuvre-lès-Nancy, 54511
Hungary7 sites
Pannónia Magánorvosi Centrum Kft.
Budapest, 1136
ENDOMEDIX Kft.
Budapest, 1139
Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja
Debrecen, 4025
Karolina Korhaz Rendelointezet
Mosonmagyaróvár, 9200
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, 6720
Tolna Megyei Balassa Janos Korhaz
Szekszárd, 7100
Javorszky Odon Korhaz
Vác, 2600
Australia5 sites
Concord Repatriation General Hospital
Concord, New South Wales, 2139
Footscray Hospital
Footscray, Victoria, 3011
Liverpool Hospital
Liverpool, New South Wales, 2170
Royal Melbourne Hospital
Parkville, Victoria, 3050
Mater Adult Hospital
South Brisbane, Queensland, 4101
Italy5 sites
Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi
Bologna, 40138
IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
Milan, 20089
Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
Palermo, 90146
Fondazione PTV Policlinico Tor Vergata
Roma, 00133
Complesso Integrato Columbus
Roma, 00168
Russia5 sites
Republican Clinical Hospital
Kazan', 420064
Stolitsa-Medikl, LLC
Moscow, 115088
SEIHPE Rostov State Medical University of MoH of RF
Rostov-on-Don, 344022
Russian Medical Military Academy na SMKirov
Saint Petersburg, 129329
Regional Clinical Hospital
Saratov, 410053
Czechia4 sites
Fakultni nemocnice u sv Anny v Brne
Brno, 656 91
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05
Hepato-Gastroenterologie HK, s. r. o.
Hradec Králové, 500 12
Nemocnice Slany
Slaný, 274 01
Germany4 sites
DRK Kliniken Berlin Westend
Berlin, 14050
Crohn-Colitis-Centre Rhein-Main
Frankfurt, 60594
Universitatsklinikum Schleswig-Holstein
Keil, 24105
Gastroenterologische Praxis Minden
Minden, 32423
New Zealand4 sites
Auckland City Hospital
Auckland, 1023
Christchurch Hospital
Christchurch, 8011
Dunedin Hospital
Dunedin, 9016
Waikato hospital
Hamilton, 3204
Canada2 sites
Hamilton Health Sciences Corporation, McMaster University Medical Centre
Hamilton, Ontario, L8N 3Z5
Winnipeg Regional Health Authority - Health Sciences Centre
Winnipeg, Manitoba, R3A 1R9
Netherlands2 sites
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
Ikazia Ziekenhuis
Rotterdam, 3083 AN
About this study
Official title: 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).
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- Apremilast, Placebo
- Keywords
- Ulcerative Colitis, Inflammatory Bowel Disease
- Medical subject headings
- Colitis, Ulcerative, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApremilastDrug
Also called CC-10004; Otezla
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Apremilast 30 mg PO BID | Experimental | 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) Receives: Drug: Apremilast |
| Apremilast 40 mg PO BID | Experimental | 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) Receives: Drug: Apremilast |
| Placebo BID | Placebo comparator | 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) Receives: Drug: Apremilast; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 12
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2014 (estimated)
- Study start8 Jan 2015
- Primary completion25 Sep 2017
- Study completion3 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02289417
- Sponsor's protocol ID
- CC-10004-UC-001
- Other IDs
- 2014-002981-64, 2014
- Acronym
- UC
- Status last verified
- Apr 2020
- First submitted
- 10 Nov 2014
- Last updated
- 7 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
- Expanded access
- Available
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.
PubMed 31926340
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02289417
- Acronym / sponsor ID
- UC / CC-10004-UC-001
- Conditions
- Ulcerative Colitis
- Keywords
- Ulcerative Colitis, Inflammatory Bowel Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 8 Jan 2015 (actual)
- Primary completion
- 25 Sep 2017 (actual)
- Study completion
- 3 Jun 2019 (actual)
- First posted
- 13 Nov 2014 (estimated)
- Results
- Posted 29 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Apremilast 30 mg PO BID | Experimental | Drug: ApremilastApremilast 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) |
| Apremilast 40 mg PO BID | Experimental | Drug: ApremilastApremilast 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) |
| Placebo BID | Placebo comparator | Drug: Apremilast, Drug: PlaceboIdentically 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApremilastAlso: CC-10004; Otezla | Drug | Apremilast 30 mg PO BID, Apremilast 40 mg PO BID, Placebo BID |
| Placebo | Drug | Placebo BID |
Primary outcome
Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12
Time frame: 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.
12 secondary outcomes
Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12
Time frame: Week 12
Percentage of Participants Who Achieved an Endoscopic Remission at Week 12
Time frame: Week 12
Percentage of Participants Who Achieved an Endoscopic Response at Week 12
Time frame: Week 12
Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12
Time frame: Week 12
Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12
Time frame: Week 12
Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12
Time frame: Week 12
Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8
Time frame: Week 8
Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8
Time frame: Week 8
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31926340Danese 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.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
99 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apremilast in people with Ulcerative Colitis, run by Amgen at 99 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 99 sites in United States, Poland, Ukraine, Bulgaria, France and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12 (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02289417, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2020.