Clinical trial NCT02289417: Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
Inflammatory Bowel Disease
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-11-13
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved an Endoscopic Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved an Endoscopic Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8
timeFrame: Week 8
measure: Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8
timeFrame: Week 8
measure: The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase
timeFrame: 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
measure: The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period
timeFrame: 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
measure: The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52
timeFrame: 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
measure: The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase)
timeFrame: 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.
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists of The Southeast
state: Alabama
city: Los Angeles
country: United States
facility: Southern California Research Institute Medical Group, Inc.
state: California
city: Bristol
country: United States
facility: Connecticut Clinical Research Foundation
state: Connecticut
city: Boynton Beach
country: United States
facility: Consultants for Clinical Research of South Florida
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Lauderdale Lakes
country: United States
facility: Precision Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic, Inc.
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group of Naples
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Worcester
country: United States
facility: UMass Medical Center
state: Massachusetts
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Troy
country: United States
facility: Center for Digestive Health Research
state: Michigan
city: Flowood
country: United States
facility: Gastrointestinal Associates PA
state: Mississippi
city: Great Neck
country: United States
facility: NYU Langone Long Island Clinical Research Associates
state: New York
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Nashville
country: United States
facility: Quality Medical Research
state: Tennessee
city: Live Oak
country: United States
facility: Digestive Research Center/ Gastroenterology Consultants of San Antonio
state: Texas
city: Pasadena
country: United States
facility: Digestive Health Specialist of Tyler
state: Texas
city: San Antonio
country: United States
facility: San Antonio Gastroenterology
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Footscray
country: Australia
facility: Footscray Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Kaspela
city: Sofia
country: Bulgaria
facility: Medical Center Asklepion - Humane Medicine Research EOOD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna ISUL EAD
city: Sofia
country: Bulgaria
facility: Clinic of Gastroenterology
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Sveta Marina EAD
city: Winnipeg
country: Canada
facility: Winnipeg Regional Health Authority - Health Sciences Centre
state: Manitoba
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation, McMaster University Medical Centre
state: Ontario
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv Anny v Brne
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Hradec Králové
country: Czechia
facility: Hepato-Gastroenterologie HK, s. r. o.
city: Slany
country: Czechia
facility: Nemocnice Slany
city: Amiens
country: France
facility: Amiens University Hospital
city: Clichy
country: France
facility: Hopital Beaujon
city: Nantes
country: France
facility: CHRU Nantes
city: Nice
country: France
facility: CHU de Nice Archet I
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Saint Priest en Jarez
country: France
facility: Centre Hospitalier Universitaire de Saint Etienne
city: Vandoeuvre les Nancy
country: France
facility: CHRU Nancy
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Westend
city: Frankfurt
country: Germany
facility: Crohn-Colitis-Centre Rhein-Main
city: Keil
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Minden
country: Germany
facility: Gastroenterologische Praxis Minden
city: Budapest
country: Hungary
facility: Pannónia Magánorvosi Centrum Kft.
city: Budapest
country: Hungary
facility: ENDOMEDIX Kft.
city: Debrecen
country: Hungary
facility: Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja
city: Mosonmagyaróvár
country: Hungary
facility: Karolina Korhaz Rendelointezet
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Szekszárd
country: Hungary
facility: Tolna Megyei Balassa Janos Korhaz
city: Vác
country: Hungary
facility: Javorszky Odon Korhaz
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi
city: Milan
country: Italy
facility: IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
city: Roma
country: Italy
facility: Complesso Integrato Columbus
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato hospital
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Bydgoszcz
country: Poland
facility: Osrodek Badan Klinicznych CLINSANTE S.C.
city: Czestochowa
country: Poland
facility: Centrum Medyczne sw. Lukasza
city: Katowice
country: Poland
facility: Economicus - NZOZ ALL-MEDICUS
city: Sopot
country: Poland
facility: Endoskopia Sp. z o.o.
city: Szczecin
country: Poland
facility: Sonomed Sp. z o.o.
city: Torun
country: Poland
facility: Gastromed Kopon Zmudzinski i Wspolnicy Sp. j. Specjalistyczne Centrum Gastrologii i Endoskopii Spec. Gabinety Lekarskie
city: Warsaw
country: Poland
facility: Centrum Zdrowia Matki, Dziecka i Mlodziezy
city: Warszawa
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
city: Wroclaw
country: Poland
facility: Lexmedica Drubajlo Hanna
city: Wroclaw
country: Poland
facility: Ars Medica
city: Kazan
country: Russian Federation
facility: Republican Clinical Hospital
city: Moscow
country: Russian Federation
facility: Stolitsa-Medikl, LLC
city: Rostov on Don
country: Russian Federation
facility: SEIHPE Rostov State Medical University of MoH of RF
city: Saratov
country: Russian Federation
facility: Regional Clinical Hospital
city: St Petersburg
country: Russian Federation
facility: Russian Medical Military Academy na SMKirov
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Clinical Hospital, Gastroenterology department, State Higher Education Institute Ivano-Frankivsk National Medical University
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Central City Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Kharkiv City Clinical Hospital 2
city: Kirovograd
country: Ukraine
facility: Private Enterprise Private Manufacture Company Acinus
city: Kremenchuk
country: Ukraine
facility: Kremenchuk City Hospital # 1 n.a O.T.Bohaievskyi
city: Lviv
country: Ukraine
facility: Lviv Emergency Clinical Hospital, Therapeutics Department No. 1
city: Odesa
country: Ukraine
facility: Municipal Institution Odesa Regional Clinical Hospital
city: Uzhgorod
country: Ukraine
facility: Central City Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Hospital n a M I Pyrohov
city: Zaporizhzhia
country: Ukraine
facility: Municipal Institution Zaporizhzhia
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.