Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— UC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02289417
• Other study ID #: CC-10004-UC-001
• Secondary ID: 2014-002981-64
• Status: Completed
• Phase: Phase 2
• Start date: January 8, 2015
• Est. completion date: June 3, 2019

Study information

• Verified date: April 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: June 3, 2019
• Est. primary completion date: September 25, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Apremilast

• Placebo

Locations

Country	Name	City	State
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Footscray Hospital	Footscray	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Mater Adult Hospital	South Brisbane	Queensland
Bulgaria	Multiprofile Hospital for Active Treatment Kaspela	Plovdiv
Bulgaria	Clinic of Gastroenterology	Sofia
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	Multiprofile Hospital for Active Treatment Sveta Marina EAD	Varna
Canada	Hamilton Health Sciences Corporation, McMaster University Medical Centre	Hamilton	Ontario
Canada	Winnipeg Regional Health Authority - Health Sciences Centre	Winnipeg	Manitoba
Czechia	Fakultni nemocnice u sv Anny v Brne	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Hepato-Gastroenterologie HK, s. r. o.	Hradec Králové
Czechia	Nemocnice Slany	Slany
France	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	Vandoeuvre les Nancy
Germany	DRK Kliniken Berlin Westend	Berlin
Germany	Crohn-Colitis-Centre Rhein-Main	Frankfurt
Germany	Universitatsklinikum Schleswig-Holstein	Keil
Germany	Gastroenterologische Praxis Minden	Minden
Hungary	ENDOMEDIX Kft.	Budapest
Hungary	Pannónia Magánorvosi Centrum 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
Italy	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	Complesso Integrato Columbus	Roma
Italy	Fondazione PTV Policlinico Tor Vergata	Roma
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Ikazia Ziekenhuis	Rotterdam
New Zealand	Auckland City Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Waikato hospital	Hamilton
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok
Poland	Osrodek Badan Klinicznych CLINSANTE S.C.	Bydgoszcz
Poland	Centrum Medyczne sw. Lukasza	Czestochowa
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	Warszawa
Poland	Ars Medica	Wroclaw
Poland	Lexmedica Drubajlo Hanna	Wroclaw
Russian Federation	Republican Clinical Hospital	Kazan
Russian Federation	Stolitsa-Medikl, LLC	Moscow
Russian Federation	SEIHPE Rostov State Medical University of MoH of RF	Rostov on Don
Russian Federation	Regional Clinical Hospital	Saratov
Russian Federation	Russian Medical Military Academy na SMKirov	St Petersburg
Ukraine	Ivano-Frankivsk Central City Clinical Hospital	Ivano-Frankivsk
Ukraine	Ivano-Frankivsk Regional Clinical Hospital	Ivano-Frankivsk
Ukraine	Regional Clinical Hospital, Gastroenterology department, State Higher Education Institute Ivano-Frankivsk National Medical University	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	Uzhgorod
Ukraine	Vinnytsia Regional Clinical Hospital n a M I Pyrohov	Vinnytsia
Ukraine	Municipal Institution Zaporizhzhia	Zaporizhzhia
United States	Consultants for Clinical Research of South Florida	Boynton Beach	Florida
United States	Connecticut Clinical Research Foundation	Bristol	Connecticut
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Digestive Health Specialists of The Southeast	Dothan	Alabama
United States	Gastrointestinal Associates PA	Flowood	Mississippi
United States	NYU Langone Long Island Clinical Research Associates	Great Neck	New York
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Precision Clinical Research, LLC	Lauderdale Lakes	Florida
United States	Digestive Research Center/ Gastroenterology Consultants of San Antonio	Live Oak	Texas
United States	Southern California Research Institute Medical Group, Inc.	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Pharmax Research Clinic, Inc.	Miami	Florida
United States	Gastroenterology Group of Naples	Naples	Florida
United States	Quality Medical Research	Nashville	Tennessee
United States	Digestive Health Specialist of Tyler	Pasadena	Texas
United States	Advanced Medical Research Center	Port Orange	Florida
United States	University of Utah	Salt Lake City	Utah
United States	San Antonio Gastroenterology	San Antonio	Texas
United States	Harborview Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Center for Digestive Health Research	Troy	Michigan
United States	UMass Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Netherlands,  New Zealand,  Poland,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.