Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis

NCT ID: NCT02289417

Last Updated: 2020-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-08
• Study Completion Date: 2019-06-03

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.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: EXPERIMENTAL

Apremilast

Intervention Type: DRUG

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)

Group Type: EXPERIMENTAL

Apremilast

Intervention Type: DRUG

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)

Group Type: PLACEBO_COMPARATOR

Apremilast

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Interventions

Apremilast

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

CC-10004; Otezla

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Digestive Health Specialists of The Southeast

Dothan, Alabama, United States

Southern California Research Institute Medical Group, Inc.

Los Angeles, California, United States

Connecticut Clinical Research Foundation

Bristol, Connecticut, United States

Consultants for Clinical Research of South Florida

Boynton Beach, Florida, United States

Avail Clinical Research, LLC

DeLand, Florida, United States

Precision Clinical Research, LLC

Lauderdale Lakes, Florida, United States

Pharmax Research Clinic, Inc.

Miami, Florida, United States

Gastroenterology Group of Naples

Naples, Florida, United States

Advanced Medical Research Center

Port Orange, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Louisville

Louisville, Kentucky, United States

UMass Medical Center

Worcester, Massachusetts, United States

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, United States

Center for Digestive Health Research

Troy, Michigan, United States

Gastrointestinal Associates PA

Flowood, Mississippi, United States

NYU Langone Long Island Clinical Research Associates

Great Neck, New York, United States

Consultants for Clinical Research

Cincinnati, Ohio, United States

Quality Medical Research

Nashville, Tennessee, United States

Digestive Research Center/ Gastroenterology Consultants of San Antonio

Live Oak, Texas, United States

Digestive Health Specialist of Tyler

Pasadena, Texas, United States

San Antonio Gastroenterology

San Antonio, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Harborview Medical Center

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

Mater Adult Hospital

South Brisbane, Queensland, Australia

Footscray Hospital

Footscray, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Multiprofile Hospital for Active Treatment Kaspela

Plovdiv, , Bulgaria

Medical Center Asklepion - Humane Medicine Research EOOD

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna ISUL EAD

Sofia, , Bulgaria

Clinic of Gastroenterology

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment Sveta Marina EAD

Varna, , Bulgaria

Winnipeg Regional Health Authority - Health Sciences Centre

Winnipeg, Manitoba, Canada

Hamilton Health Sciences Corporation, McMaster University Medical Centre

Hamilton, Ontario, Canada

Fakultni nemocnice u sv Anny v Brne

Brno, , Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Hepato-Gastroenterologie HK, s. r. o.

Hradec Králové, , Czechia

Nemocnice Slany

Slaný, , Czechia

Amiens University Hospital

Amiens, , France

Hopital Beaujon

Clichy, , France

CHRU Nantes

Nantes, , France

CHU de Nice Archet I

Nice, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Centre Hospitalier Universitaire de Saint Etienne

Saint-Priest-en-Jarez, , France

CHRU Nancy

Vandœuvre-lès-Nancy, , France

DRK Kliniken Berlin Westend

Berlin, , Germany

Crohn-Colitis-Centre Rhein-Main

Frankfurt, , Germany

Universitatsklinikum Schleswig-Holstein

Keil, , Germany

Gastroenterologische Praxis Minden

Minden, , Germany

Pannónia Magánorvosi Centrum Kft.

Budapest, , Hungary

ENDOMEDIX Kft.

Budapest, , Hungary

Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja

Debrecen, , Hungary

Karolina Korhaz Rendelointezet

Mosonmagyaróvár, , Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, , Hungary

Tolna Megyei Balassa Janos Korhaz

Szekszárd, , Hungary

Javorszky Odon Korhaz

Vác, , Hungary

Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi

Bologna, , Italy

IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center

Milan, , Italy

Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello

Palermo, , Italy

Fondazione PTV Policlinico Tor Vergata

Roma, , Italy

Complesso Integrato Columbus

Roma, , Italy

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Ikazia Ziekenhuis

Rotterdam, , Netherlands

Auckland City Hospital

Auckland, , New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Dunedin Hospital

Dunedin, , New Zealand

Waikato hospital

Hamilton, , New Zealand

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, , Poland

Osrodek Badan Klinicznych CLINSANTE S.C.

Bydgoszcz, , Poland

Centrum Medyczne sw. Lukasza

Częstochowa, , Poland

Economicus - NZOZ ALL-MEDICUS

Katowice, , Poland

Endoskopia Sp. z o.o.

Sopot, , Poland

Sonomed Sp. z o.o.

Szczecin, , Poland

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

Torun, , Poland

Centrum Zdrowia Matki, Dziecka i Mlodziezy

Warsaw, , Poland

Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED

Warsaw, , Poland

Lexmedica Drubajlo Hanna

Wroclaw, , Poland

Ars Medica

Wroclaw, , Poland

Republican Clinical Hospital

Kazan', , Russia

Stolitsa-Medikl, LLC

Moscow, , Russia

SEIHPE Rostov State Medical University of MoH of RF

Rostov-on-Don, , Russia

Russian Medical Military Academy na SMKirov

Saint Petersburg, , Russia

Regional Clinical Hospital

Saratov, , Russia

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

Ivano-Frankivsk, , Ukraine

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, , Ukraine

Ivano-Frankivsk Central City Clinical Hospital

Ivano-Frankivsk, , Ukraine

Kharkiv City Clinical Hospital 2

Kharkiv, , Ukraine

Private Enterprise Private Manufacture Company Acinus

Kirovograd, , Ukraine

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

Kremenchuk, , Ukraine

Lviv Emergency Clinical Hospital, Therapeutics Department No. 1

Lviv, , Ukraine

Municipal Institution Odesa Regional Clinical Hospital

Odesa, , Ukraine

Central City Clinical Hospital

Uzhhorod, , Ukraine

Vinnytsia Regional Clinical Hospital n a M I Pyrohov

Vinnytsia, , Ukraine

Municipal Institution Zaporizhzhia

Zaporizhzhia, , Ukraine

Countries

United States; Australia; Bulgaria; Canada; Czechia; France; Germany; Hungary; Italy; Netherlands; New Zealand; Poland; Russia; Ukraine

References

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.

Reference Type: DERIVED

PMID: 31926340 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2014-002981-64

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-10004-UC-001

Identifier Type: -

Identifier Source: org_study_id