Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis

NCT02289417 | Completed Phase 2 Results DMC

• 2 other identifiers: CC-10004-UC-0012014-002981-64
• Study Type: interventional
• Target: 170
• Locations: 14 countries
• Sites: 99

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).

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; Inflammatory Bowel Disease

Outcome Measures

Primary Outcomes (1)

• 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 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

  Week 12

• Percentage of Participants Who Achieved an Endoscopic Remission at Week 12

  Week 12

• Percentage of Participants Who Achieved an Endoscopic Response at Week 12

  Week 12

• Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12

  Week 12

• Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12

  Week 12

Study Arms (3)

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)

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)

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)

Drug: Apremilast; Drug: Placebo

Interventions

Apremilast DRUG

Also known as: CC-10004; Otezla

Apremilast 30 mg PO BID; Apremilast 40 mg PO BID; Placebo BID

Placebo DRUG

Placebo BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[MTX\]).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (99)

Digestive Health Specialists of The Southeast

Dothan, Alabama, 36305, United States

Location

Southern California Research Institute Medical Group, Inc.

Los Angeles, California, 90045, United States

Location

Connecticut Clinical Research Foundation

Bristol, Connecticut, 06010, United States

Location

Consultants for Clinical Research of South Florida

Boynton Beach, Florida, 33426, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

Precision Clinical Research, LLC

Lauderdale Lakes, Florida, 33319, United States

Location

Pharmax Research Clinic, Inc.

Miami, Florida, 33126, United States

Location

Gastroenterology Group of Naples

Naples, Florida, 34102, United States

Location

Advanced Medical Research Center

Port Orange, Florida, 32127, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

UMass Medical Center

Worcester, Massachusetts, 01655, United States

Location

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, 48047, United States

Location

Center for Digestive Health Research

Troy, Michigan, 48098, United States

Location

Gastrointestinal Associates PA

Flowood, Mississippi, 39232, United States

Location

NYU Langone Long Island Clinical Research Associates

Great Neck, New York, 11021, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45219, United States

Location

Quality Medical Research

Nashville, Tennessee, 37211, United States

Location

Digestive Research Center/ Gastroenterology Consultants of San Antonio

Live Oak, Texas, 78233, United States

Location

Digestive Health Specialist of Tyler

Pasadena, Texas, 77505, United States

Location

San Antonio Gastroenterology

San Antonio, Texas, 78229, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Mater Adult Hospital

South Brisbane, Queensland, 4101, Australia

Location

Footscray Hospital

Footscray, Victoria, 3011, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Multiprofile Hospital for Active Treatment Kaspela

Plovdiv, 4002, Bulgaria

Location

Medical Center Asklepion - Humane Medicine Research EOOD

Sofia, 1303, Bulgaria

Location

University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia

Sofia, 1407, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD

Sofia, 1431, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna ISUL EAD

Sofia, 1527, Bulgaria

Location

Clinic of Gastroenterology

Sofia, 1784, Bulgaria

Location

Multiprofile Hospital for Active Treatment Sveta Marina EAD

Varna, 9010, Bulgaria

Location

Winnipeg Regional Health Authority - Health Sciences Centre

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Hamilton Health Sciences Corporation, McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Fakultni nemocnice u sv Anny v Brne

Brno, 656 91, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Hepato-Gastroenterologie HK, s. r. o.

Hradec Králové, 500 12, Czechia

Location

Nemocnice Slany

Slaný, 274 01, Czechia

Location

Amiens University Hospital

Amiens, 80054, France

Location

Hopital Beaujon

Clichy, 92110, France

Location

CHRU Nantes

Nantes, 602 00, France

Location

CHU de Nice Archet I

Nice, 06202, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Universitaire de Saint Etienne

Saint-Priest-en-Jarez, 42055, France

Location

CHRU Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

DRK Kliniken Berlin Westend

Berlin, 14050, Germany

Location

Crohn-Colitis-Centre Rhein-Main

Frankfurt, 60594, Germany

Location

Universitatsklinikum Schleswig-Holstein

Keil, 24105, Germany

Location

Gastroenterologische Praxis Minden

Minden, 32423, Germany

Location

Pannónia Magánorvosi Centrum Kft.

Budapest, 1136, Hungary

Location

ENDOMEDIX Kft.

Budapest, 1139, Hungary

Location

Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja

Debrecen, 4025, Hungary

Location

Karolina Korhaz Rendelointezet

Mosonmagyaróvár, 9200, Hungary

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, 6720, Hungary

Location

Tolna Megyei Balassa Janos Korhaz

Szekszárd, 7100, Hungary

Location

Javorszky Odon Korhaz

Vác, 2600, Hungary

Location

Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi

Bologna, 40138, Italy

Location

IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center

Milan, 20089, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello

Palermo, 90146, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Roma, 00133, Italy

Location

Complesso Integrato Columbus

Roma, 00168, Italy

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Ikazia Ziekenhuis

Rotterdam, 3083 AN, Netherlands

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Dunedin Hospital

Dunedin, 9016, New Zealand

Location

Waikato hospital

Hamilton, 3204, New Zealand

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, 15-276, Poland

Location

Osrodek Badan Klinicznych CLINSANTE S.C.

Bydgoszcz, 85-794, Poland

Location

Centrum Medyczne sw. Lukasza

Częstochowa, 42 202, Poland

Location

Economicus - NZOZ ALL-MEDICUS

Katowice, 40 659, Poland

Location

Endoskopia Sp. z o.o.

Sopot, 81-756, Poland

Location

Sonomed Sp. z o.o.

Szczecin, 71-685, Poland

Location

Gastromed Kopon Zmudzinski i Wspolnicy Sp. j. Specjalistyczne Centrum Gastrologii i Endoskopii Spec. Gabinety Lekarskie

Torun, 40 659, Poland

Location

Centrum Zdrowia Matki, Dziecka i Mlodziezy

Warsaw, 00-632, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED

Warsaw, 03-563, Poland

Location

Lexmedica Drubajlo Hanna

Wroclaw, 03-580, Poland

Location

Ars Medica

Wroclaw, 53-333, Poland

Location

Republican Clinical Hospital

Kazan', 420064, Russia

Location

Stolitsa-Medikl, LLC

Moscow, 115088, Russia

Location

SEIHPE Rostov State Medical University of MoH of RF

Rostov-on-Don, 344022, Russia

Location

Russian Medical Military Academy na SMKirov

Saint Petersburg, 129329, Russia

Location

Regional Clinical Hospital

Saratov, 410053, Russia

Location

Regional Clinical Hospital, Gastroenterology department, State Higher Education Institute Ivano-Frankivsk National Medical University

Ivano-Frankivsk, 58001, Ukraine

Location

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, 76008, Ukraine

Location

Ivano-Frankivsk Central City Clinical Hospital

Ivano-Frankivsk, 76018, Ukraine

Location

Kharkiv City Clinical Hospital 2

Kharkiv, 61037, Ukraine

Location

Private Enterprise Private Manufacture Company Acinus

Kirovograd, 25006, Ukraine

Location

Kremenchuk City Hospital # 1 n.a O.T.Bohaievskyi

Kremenchuk, 39617, Ukraine

Location

Lviv Emergency Clinical Hospital, Therapeutics Department No. 1

Lviv, 79059, Ukraine

Location

Municipal Institution Odesa Regional Clinical Hospital

Odesa, 65025, Ukraine

Location

Central City Clinical Hospital

Uzhhorod, 88000, Ukraine

Location

Vinnytsia Regional Clinical Hospital n a M I Pyrohov

Vinnytsia, 21018, Ukraine

Location

Municipal Institution Zaporizhzhia

Zaporizhzhia, 69600, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 31926340 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

apremilast

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: November 13, 2014
• Study Start: January 8, 2015
• Primary Completion: September 25, 2017
• Study Completion: June 3, 2019
• Last Updated: May 7, 2020
• Results First Posted: October 29, 2018

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

CZ (4); UA (11); FR (7); IT (5); BU (7); CA (2); DE (4); NL (2); PL (11); RU (5); AU (5); US (25); HU (7); NZ (4)