Efficacy and Safety Study of Ontamalimab as Induction Therapy in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 305)

Crohn's Disease Clinical Trial

— CARMEN CD 305  

Official title:

A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 305)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03559517
• Other study ID #: SHP647-305
• Status: Terminated
• Phase: Phase 3
• Start date: August 29, 2018
• Est. completion date: October 8, 2020

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of ontamalimab in inducing clinical remission and endoscopic response in participants with moderate to severe Crohn's Disease.

Description:

27Mar2020: Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: October 8, 2020
• Est. primary completion date: July 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 80 Years

Eligibility

Inclusion Criteria:

• Participants must be between greater than or equal to (> =) 16 and less than or equal to (<=) 80 years of age; participants less than (<) 18 years of age must weigh >=40 kg and must have body mass index >=16.5 kilogram per meter square (kg/m^2)
• Participants must have active moderate to severe ileal (terminal ileum), ileocolic, or

colonic CD at baseline (Visit 2) as defined by:

1. CDAI score between 220 and 450 (inclusive) AND

2. Meeting the following subscores in the 2 item PRO:

i. Abdominal pain subscore >= 5 (average worst daily pain on the 11 point NRS) and abdominal pain subscore >= 2 (average daily pain on the 4-point abdominal pain variable of CDAI) over the 7 most recent days out of the 10 days before colonoscopy preparation (may or may not be contiguous) AND/OR ii. Average of the daily stool frequency subscore >=4 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days out of the 10 days before colonoscopy preparation (may or may not be contiguous) c. Presence of ulcerations that are characteristic to CD, as determined by a colonoscopy performed during screening, and as defined by the SES-CD >6 (SES CD >=4 for isolated ileitis) Note that the participant must be confirmed as meeting the CDAI score and PRO subscore requirements before a colonoscopy is done

• Participants must have a documented diagnosis (endoscopic with histology) of CD for

>=3 months before screening. Documented diagnosis is defined as:

1. A biopsy report in which the description of the histological findings is consistent with the CD diagnosis AND

2. A report documenting disease duration based upon prior colonoscopy Note: If a biopsy report is not available in the source document at the time of screening, a biopsy must be performed during the screening colonoscopy and the histology report should be consistent with the CD diagnosis. If the histology description does not support the CD diagnosis at this time point, the participant should not be randomized

• Participants must be willing and able to undergo a colonoscopy during screening after all other inclusion criteria have been met
• Participants must have had an inadequate response to, or lost response to, or had an intolerance to at least 1 conventional treatment such as sulfasalazine or mesalamine (5-aminosalicylic acid [5-ASA]), glucocorticoids, or immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP] or methotrexate [MTX]) or anti-tumor necrosis factor (anti-TNF). Participants who have had an inadequate response to sulfasalazine or mesalamine should have also failed at least 1 other conventional treatment such as glucocorticoids
• Participants receiving any treatment(s) for CD are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time
• Participants are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential. Males and females of reproductive potential who are sexually active must agree to use appropriate contraception (ie, highly effective methods for female and medically appropriate methods for male study participants, for the duration of the study

Exclusion criteria:

• Participants with indeterminate colitis, microscopic colitis, nonsteroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of UC
• Participants with colonic dysplasia or neoplasia. (Participants with prior history of adenomatous polyps will be eligible if the polyps have been completely removed)
• Participants with past medical history or presence of toxic megacolon
• Participants with presence of enterovesical (ie, between the bowel and urinary bladder) or enterovaginal fistulae
• Participants with current symptomatic diverticulitis or diverticulosis
• Participants with clinically significant obstructive colonic stricture, or who have a history of bowel surgery within 6 months before screening, or who are likely to require surgery for CD during the treatment period. Participants who have undergone previous colonic resection or ileocolectomy more than 6 months before screening must have at least 25 cm of colon remaining
• Participants with past medical history of multiple small bowel resections resulting in clinically significant short bowel syndrome
• Participants requiring total parenteral nutrition
• Participants with past medical history of bowel surgery resulting in an existing or current stoma. Participants who had a j-pouch are excluded as a j-pouch could result in a stoma
• Participants have had prior treatment with ontamalimab (formerly PF-00547659; SHP647)
• Participants with known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients
• Participants have received any nonbiologic treatment with immunomodulatory properties (other than AZA, 6-MP, or MTX) or continuous antibiotics (>2 weeks) for the treatment of CD within 30 days before baseline (Visit 2)
• Participants have received anti-TNF treatment within 60 days before baseline (Visit 2)
• Participants have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline (Visit 2)
• Participants have ever received anti-integrin/adhesion molecule treatment (eg, natalizumab,vedolizumab, efalizumab, etrolizumab, or any other investigational anti-integrin/adhesion molecule)
• Participants have received lymphocytes apheresis or selective monocyte granulocytes apheresis within 60 days before baseline (Visit 2)
• Participants have received enteral nutrition treatment within 30 days before baseline (Visit 2)
• Participants have received parenteral or rectal glucocorticoids or rectal 5-ASA within 14 days before screening colonoscopy
• Participants have taken >20 milligram per day(mg/day) of prednisone, >9 mg/day of budesonide, or equivalent oral systemic corticosteroid dose within 14 days before baseline (Visit 2) or have taken >=40 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 6 weeks before baseline (Visit 2)
• Participants have participated in other investigational studies within either 30 days or 5 half-lives of investigational product used in the study (whichever is longer) before screening (Visit 1)
• Participants have received a live (attenuated) vaccine within 30 days before the baseline visit (Visit 2)
• Participants with active enteric infections (positive stool culture and sensitivity), Clostridium difficile infection or pseudomembranous colitis (subjects with C. difficile infection at screening may be allowed retest after treatment), evidence of active cytomegalovirus infection or Listeria monocytogenes, known active invasive fungal infections such as histoplasmosis or parasitic infections, clinically significant underlying disease that could predispose the subjects to infections, or a history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before the baseline visit (Visit 2)
• Participants with abnormal chest x-ray or other imaging findings at screening (Visit 1), such as presence of active tuberculosis (TB), general infections, heart failure, or malignancy (A chest x-ray, computed tomography scan, etc, performed up to 12 weeks before study entry [screening, Visit 1] may be used if available; documentation of the official reading must be located and available in the source documentation)
• Participants with evidence of active or latent infection with Mycobacterium tuberculosis (TB) or participants with this history who have not completed a generally accepted full course of treatment before baseline (Visit 2) are excluded All other participants must have either the Mantoux (purified protein derivative [PPD]) tuberculin skin test or interferon-gamma release assay (IGRA) performed
• Participants who have no history of previously diagnosed active or latent TB are excluded if they have a positive Mantoux (PPD) tuberculin skin test (ie >= 5 millimeter [mm] induration) or a positive IGRA (the latter to be tested at the site's local laboratory) during screening or within 12 weeks before screening If the IGRA cannot be performed locally, a central laboratory may be used, with prior agreement

from the sponsor:

1. An IGRA is strongly recommended for participants with a prior Bacillus Calmette-Guérin vaccination but may be used for any participant Documentation of IGRA product used and the test result must be in the participant's source documentation if performed locally Acceptable IGRA products include QuantiFERON-TB Gold Plus In-Tube Test

2. If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result is obtained, enrollment may proceed In participants with no history of treated active or latent TB, a positive test on repeat will exclude the participantParticipants with a history of active or latent TB infection must follow instructions for "Participants with a prior diagnosis of active or latent TB are excluded unless both of the following criteria are met" in this criterion

3. Participants with repeat indeterminate IGRA results, with no prior TB history, may be enrolled after consultation with a pulmonary or infectious disease specialist who determines low risk of infection (ie, participant would be acceptable for immunosuppressant [eg, anti-TNF] treatment without additional action) This consultation must be included in source documentation Results from a chest x-ray, taken within the 12 weeks before or during screening (Visit 1)must show no abnormalities suggestive of active TB infection as determined by a qualified medical specialist

• Participants with a pre-existing demyelinating disorder such as multiple sclerosis or new onset seizures, unexplained sensory motor, or cognitive behavioral, neurological deficits, or significant abnormalities noted during screening
• Participants with any unexplained symptoms suggestive of PML based on the targeted neurological assessment during the screening period
• Participants with a transplanted organ. Skin grafts to treat pyoderma gangrenosum are allowed
• Participants with a significant concurrent medical condition at the time of screening

(Visit 1) or baseline (Visit 2), including, but not limited to, the following:

1. Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, GI [except disease under study], endocrine, cardiovascular, pulmonary, immunologic [eg, Felty's syndrome], or local active infection/infectious illness) that, in the investigator's judgment will substantially increase the risk to the subject if he or she participates in the study

2. Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence)

3. Presence of acute coronary syndrome (eg, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening (Visit 1)

4. History of significant cerebrovascular disease within 24 weeks before screening (Visit 1)

• Participants who have had significant trauma or major surgery within 4 weeks before the screening (Visit 1), or with any major elective surgery scheduled to occur during the study.
• Participant with evidence of cirrhosis with or without decompensation (ie, esophageal varices, hepatic encephalopathy, portal hypertension, ascites)
• Participant with primary sclerosing cholangitis
• Participant with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) Note: if a subject tests negative for HBsAg, but positive for HBcAb, the subject would be considered eligible if no presence of hepatitis B virus (HBV) DNA is confirmed by HBV DNA polymerase chain reaction (PCR) reflex testing performed in the central laboratory
• Participant with chronic hepatitis C virus (HCV) (positive HCV antibody [HCVAb] and HCV RNA) Note: Participant who are HCVAb positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCV RNA at least 12 weeks prior to baseline])
• Participant with any of the following abnormalities in hematology and/or serum chemistry profiles during screening (Visit 1) Note: Screening laboratory tests, if the results are considered by the investigator to be transient and inconsistent with the subject's clinical condition, may be repeated once during the screening period for confirmation results must be reviewed for eligibility prior to the screening colonoscopy procedure

1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels >=3.0 × the upper limit of normal (ULN)

2. Total bilirubin level >=1.5 × ULN or >2.0 × ULN if the subject has a known documented history of Gilbert's syndrome

3. Hemoglobin level less than or equal to(<=80) gram per liter(g/L) (8.0 g/deciliter[dL])

4. Platelet count <=100× 10^9/L (100,000 cells/mm^3) or >=1000 × 10^9/L (1,000,000 cells/mm^3)*

5. White blood cell count <=3.5 × 10^9/L (3500 cells/mm^3)

6. Absolute neutrophil count <2 × 10^9/L (2000 cells/mm^3)

7. Serum creatinine level >1.5 × ULN or estimated glomerular filtration rate <30 millilter per minute (mL/min)/173 meter square (m^2) based on the abbreviated Modification of Diet in RenalDisease Study Equation Note: if platelet count is <150,000 cells/mm3, a further evaluation should be performed to rule out cirrhosis, unless another etiology has already been identified

• Participant with known human immunodeficiency virus (HIV) infection based on documented history with positive serological test, or positive HIV serologic test at screening, tested at the site's local laboratory in accordance with country requirements or tested at the central laboratory Note: A documented negative HIV test within 6 months of screening is acceptable and does not need to be repeated
• With known human immunodeficiency virus (HIV) infection based on documented history with positive serological test, or positive HIV serologic test at screening, tested at the site's local laboratory in accordance with country requirements or tested at the central laboratory.
• Participants who have, or who have a history of (within 2 years before screening), serious psychiatric disease, alcohol dependency, or substance/drug abuse or dependency of any kind including abuse of medicinal marijuana (cannabis) NOTE: The above Inclusion/Exclusion criteria are NOT exhaustive and other Inclusion/ Exclusion criteria as defined in the protocol may apply.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Biological:
• Ontamalimab
Subcutaneous injection of ontamalimab will be administered using a prefilled syringe.

Other:
• Placebo
Subcutaneous injection of placebo matched with ontamalimab will be administered using a prefilled syringe.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	St Vincents Hospital Melbourne - PPDS	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Mater Hospital Brisbane	South Brisbane	Queensland
Austria	LKH-Universitätsklinikum Klinikum Graz	Graz	Steiermark
Austria	Salzburger Landeskliniken	Salzburg
Austria	Klinikum Wels-Grieskirchen GmbH	Vienna	Wien
Austria	Medizinische Universitat Wien (Medical University of Vienna)	Wien
Croatia	Opca bolnica Bjelovar	Bjelovar
Croatia	Clinical Hospital Centre Osijek	Osijek
Croatia	General Hospital Virovitica	Virovitica
Croatia	University Hospital Center Zagreb	Zagreb	Grad Zagreb
Germany	Universitätsklinikum der RWTH Aachen	Aachen	Nordrhein-Westfalen
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Gastroenterologische Facharztpraxis am Mexikoplatz	Berlin-Zehlendorf
Germany	Sana Klinikum Biberach	Biberach an der Riss
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitatsklinikum Jena	Jena	Thüringen
Germany	Universitatsklinikum Schleswig-Holstein	Kiel	Schleswig-Holstein
Germany	Uniklinik Köln	Köln	Nordrhein-Westfalen
Germany	Klinikum rechts der Isa der Technischen Universitaet Muenchen	Munich
Germany	Gastro Campus Research GbR	Münster	Nordrhein-Westfalen
Israel	Hadassah Medical Center - PPDS	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Galilee Medical Center	Nahariya
Israel	Baruch Padeh Poriya Medical Center	Tiberias
Italy	Azienda Ospedaliera Mater Domini Di Catanzaro	Catanzaro	Calabria
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze	Toscana
Italy	Azienda Ospedaliero Universitaria Di Modena Policlinico	Modena	Emilia-Romagna
Italy	Ospedale Sacro Cuore Don Calabria	Negrar	Veneto
Italy	A.O.U. Maggiore della Carità	Novara
Italy	Fondazione IRCCS Policlinico San Matteo di Pavia	Pavia
Italy	La Sapienza-Università di Roma-Policlinico Umberto I	Roma
Italy	Istituto Clinico Humanitas	Rozzano (MI)
Italy	Ospedale Casa Sollievo Della Sofferenza IRCCS	San Giovanni Rotondo
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino
Japan	Hidaka Coloproctology Clinic	Kurume-shi
Japan	Jikei University Hospital	Minato-ku	Tokyo
Japan	Aichi Medical University Hospital	Nagakute
Japan	Nishinomiya Municipal Central Hospital	Nishinomiya
Japan	Ome Municipal General Hospital	Ome	Tokyo
Japan	Onomichi General Hospital	Onomichi
Japan	Shiga University of Medical Science Hospital	Otsu-Shi
Japan	Sapporo Higashi Tokushukai Hospital	Sapporo
Japan	Sapporo Tokushukai Hospital	Sapporo-shi	Hokkaidô
Japan	Colo-Proctology Center Matsushima Clinic	Yokohama
Lithuania	Vilnius City Clinical Hospital	Vilnius
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Netherlands	Academisch Medisch Centrum Amsterdam	Amsterdam
Netherlands	NWZ, location Alkmaar	Den Helder	Noord-Holland
Netherlands	ETZ-Elisabeth	Tilburg	Noord-Brabant
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok	Podlaskie
Poland	Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Vitamed Galaj i Cichomski sp.j.	Bydgoszcz	Kujawsko-pomorskie
Poland	Centrum Medyczne Czestochowa - PRATIA - PPDS	Czestochowa
Poland	Centrum Medyczne Gdynia - PRATIA - PPDS	Gdynia
Poland	BioVirtus Centrum Medyczne	Józefów
Poland	NZOZ All Medicus	Katowice
Poland	Szpital Specjalistyczny sw Lukasza - Oddzial Gastroenterologii	Konskie	Swietokrzyskie
Poland	Instytut Centrum Zdrowia Matki Polki	Lodz
Poland	Med Gastr Sp.z.o.o Sp.k	Lodz
Poland	Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Sp. J.	Lódz	Lódzkie
Poland	Niepubliczny Zaklad Opieki Zdrowotnej CENTRUM MEDYCZNE Szpital Swietej Rodziny	Lódz	Lódzkie
Poland	Twoja Przychodnia - Centrum Medyczne Nowa Sol	Nowa Sól
Poland	Clinical Research Center Spólka z Ograniczona Odpowiedzialnoscia, Medic-R Spólka Komandytowa	Poznan
Poland	Korczowski Bartosz, Gabinet Lekarski	Rzeszow
Poland	Endoskopia Sp. z o.o.	Sopot	Pomorskie
Poland	Sonomed Sp. z o.o.	Szczecin
Poland	Twoja Przychodnia - Szczecinskie Centrum Medyczne	Szczecin	Zachodniopomorskie
Poland	Gastromed Kopon Zmudzinski i Wspolnicy Sp.j.Specjalistyczne Centrum Gastrologii i Endoskopii Specj	Torun	Kujawsko-pomorskie
Poland	Centralny Szpital Kliniczny MSW	Warszawa
Poland	Centrum Medyczne Warszawa - PRATIA - PPDS	Warszawa	Mazowieckie
Poland	Centrum Zdrowia M D M	Warszawa
Poland	Miedzyleski Szpital Specjalistyczny w Warszawie	Warszawa	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa	Mazowieckie
Poland	Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED	Warszawa	Mazowieckie
Poland	Centrum Diagnostyczno - Lecznicze Barska sp. z o.o.	Wloclawek	Kujawsko-pomorskie
Poland	Lexmedica	Wroclaw	Dolnoslaskie
Poland	Melita Medical	Wroclaw	Dolnoslaskie
Poland	Samodzielny Publiczny Szpital Wojewodzki im. Papieza Jana Pawla II	Zamosc
Romania	Colentina Clinical Hospital	Bucharest
Romania	Dr.Carol Davila Emergency University Central Military Hospital	Bucharest
Romania	Emergency University Hospital	Bucharest
Romania	Fundeni Clinical Institute	Bucharest
Romania	Prof. Dr. Matei Bals Institute of Infectious Diseases	Bucharest
Romania	Sana Monitoring SRL	Bucharest	Bucuresti
Romania	Centrul Medical Hifu Terramed Conformal S.R.L.	Bucuresti
Romania	Cluj-Napoca Emergency Clinical County Hospital	Cluj-Napoca	Cluj
Romania	Affidea Romania SRL	Constanta
Romania	Gastromedica SRL	Iasi
Romania	Dr. Tirnaveanu Amelita Private Practice	Oradea
Romania	Dr. Goldis Gastroenterology Center SRL	Timisoara
Russian Federation	Rostov State Medical University	Rostov-on-Don
Russian Federation	Russian Medical Military Academy n.a. S.M. Kirov	Saint Petersburg
Russian Federation	Medical University Reaviz	Samara
Russian Federation	Private Healthcare Institution Clinical Hospital RZD-Medicina of Samara city	Samara
Russian Federation	SHI Regional Clinical Hospital	Saratov
Russian Federation	St. Elizabeth Municipal Clinical Hospital	St. Petersburg
Serbia	Clinical Hospital Center ''Bezanijska Kosa''	Belgrade
Serbia	University Clinical Center Kragujevac	Kragujevac	Šumadijski Okrug
Serbia	University Clinical Center Nis	Nis
Serbia	General Hospital Vrsac	Vrsac
Serbia	Clinical Hospital Center Zemun	Zemun
South Africa	Dr JP Wright	Claremont	Western Cape
South Africa	CLINRESCO, ARWYP Medical Suites	Johannesburg	Gauteng
South Africa	Dr. J Breedt	Pretoria	Gauteng
South Africa	Emmed Research	Pretoria	Gauteng
United Kingdom	Aberdeen Royal Infirmary - PPDS	Aberdeen
United Kingdom	Royal Gwent Hospital - PPDS	Newport
United Kingdom	North Tyneside General Hospital	North Shields	Northumberland
United Kingdom	New Cross Hospital	Wolverhampton
United States	Inquest Clinical Research/Coastal Gastroenterology Associates, PA - TDDC - PPDS	Baytown	Texas
United States	HP Clinical Research	Bountiful	Utah
United States	New York Total Medical Care PC	Brooklyn	New York
United States	Consultants For Clinical Research Inc	Cincinnati	Ohio
United States	Consultants For Clinical Research Inc	Cincinnati	Ohio
United States	Asthma and Allergy Associates PC - CRN - PPDS	Colorado Springs	Colorado
United States	Peak Gastroenterology Associates	Colorado Springs	Colorado
United States	Northside Gastroenterology	Cypress	Texas
United States	Consultants For Clinical Research Inc	Fairfield	Ohio
United States	Gastro One	Germantown	Tennessee
United States	Clinical Trials of SWLA LLC	Lake Charles	Louisiana
United States	OM Research LLC - Lancaster - ClinEdge - PPDS	Lancaster	California
United States	Atria Clinical Research - Clinedge - PPDS	Little Rock	Arkansas
United States	Advanced Clinical Research Network	Miami	Florida
United States	Laporte County Institute For Clinical Research	Michigan City	Indiana
United States	Gastroenterology Group of Naples	Naples	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Omega Research Consultants LLC - Clinedge - PPDS	Orlando	Florida
United States	Inland Empire Liver Foundation	Rialto	California
United States	East Coast Institute for Research, LLC	Saint Augustine	Florida
United States	Louisiana Research Center LLC	Shreveport	Louisiana
United States	Piedmont Healthcare	Statesville	North Carolina
United States	CATS Research Center - University of Arizona	Tucson	Arizona
United States	Advanced Gastroenterology-Union City	Union City	Tennessee
United States	Digestive Disease Associates	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Croatia,  Germany,  Israel,  Italy,  Japan,  Lithuania,  Netherlands,  Poland,  Romania,  Russian Federation,  Serbia,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinical Remission Based on 2-item Patient-reported Outcome (PRO) at Week 16	Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain less than or equal to (<=) 3 (based on 11 point numerical rating scale [NRS] ranging from 0 [no pain] to 10 [worst imaginable pain]); and average daily stool frequency <=2 of type 6/7 (very soft stools/liquid stools) as per the Bristol Stool Form Scale (BSFS) over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Participants with missing data at Week 16 or discontinuation before Week 16 were considered failures. Number of participants with clinical remission were reported.	At Week 16
Primary	Number of Participants With Endoscopic Response at Week 16	Endoscopic response was defined as a decrease in Simple Endoscopic Score for Crohn's disease (SES-CD) of at least 25 percent (%) from baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Participants with missing data at Week 16 or who discontinued before Week 16 were considered failures. Number of participants with endoscopic response were reported.	At Week 16
Secondary	Number of Participants With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 16	Clinical remission was defined as a CDAI score of <150. CDAI assessed CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass,. physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity. Number of participants with clinical remission as measured by CDAI were reported.	At Week 16
Secondary	Number of Participants With Enhanced Endoscopic Response at Week 16	Enhanced endoscopic response was defined as a decrease in SES-CD by matching segments of at least 50% from baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Participants with missing data at Week 16 or who discontinued before Week 16 were considered non-responders. Number of participants with enhanced endoscopic response were reported.	At Week 16
Secondary	Number of Participants With Clinical Remission Based on 2-item PRO With 4-point Scale for Abdominal Pain at Week 16	Clinical remission was defined by 2-item PRO subs-cores of average daily abdominal pain <=1 (based on the 4 point scale, with scores ranging from 0 [none] to 3 [severe]) over the 7 most recent days and average daily stool frequency <=3 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Participants with missing data at Week 16 or who discontinued before Week 16 were considered failures. Number of participants with enhanced endoscopic response were reported.	At Week 16
Secondary	Number of Participants With Clinical Response Based on 2-item PRO With 2 Criteria at Week 16	Clinical response was measured by 2-item PRO and defined as meeting at least 1 of the following 2 criteria: 1)A decrease of greater than or equal to (>=) 30% and at least 2 points from baseline in the average daily worst abdominal pain over the 7 most recent days, with the average daily stool frequency of type 6/7 (very soft stools/liquid stools) either a) not worsening from baseline and/or b) average daily stool frequency <=2 of type 6/7 as per the BSFS over the 7 most recent days; 2)A decrease of >=30% from baseline in the average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days, with the average daily worst abdominal pain either a) not worsening from baseline and/or b) worst daily abdominal pain <=3 (based on 11-point NRS) over the 7 most recent days. Participants with missing data at Week16 or who discontinued before Week 16 were considered failures. Number of participants with clinical response were reported.	At Week 16
Secondary	Number of Participants With Clinical Remission Based on 2-Item PRO With Endoscopic Response at Week 16	Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain <=3 (based on 11 point NRS ranging from 0 [no pain] to 10 [worst imaginable pain]) over the 7 most recent days and average daily stool frequency <=2 of type 6/7 (very soft stools/liquid stools) as per BSFS ranging from type 1 (separate hard lumps-like stools) to type 7 (entirely liquid stools) over the 7 most recent days. Endoscopic response was defined as a decrease in SES CD of at least 25% from baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Participants with missing data at Week 16 or who discontinued before Week 16 were considered failures. Number of participants with clinical remission and endoscopic response were reported.	At Week 16
Secondary	Number of Participants With Complete Endoscopic Healing at Week 16	Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain <=3 (based on 11 point NRS ranging from 0 [no pain] to 10 [worst imaginable pain]) over the 7 most recent days and average daily stool frequency <=2 of type 6/7 (very soft stools/liquid stools) as per BSFS ranging from type 1 (separate hard lumps-like stools) to type 7 (entirely liquid stools) over the 7 most recent days. Endoscopic response was defined as a decrease in SES CD of at least 25% from baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Participants with missing data at Week 16 or who discontinued before Week 16 were considered failures. Number of participants with complete endoscopic healing were reported.	At Week 16
Secondary	Number of Participants With Clinical Response as Measured by CDAI-100 at Week 16	Clinical response is measured by at least a 100-point reduction in the CDAI from baseline (CDAI-100 response). CDAI assesses CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity.	At Week 16
Secondary	Number of Participants With Clinical Response as Measured by CDAI-70 at Week 16	Clinical response is measured by at least a 70-point reduction in the CDAI from baseline (CDAI-70 response). CDAI assesses CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity.	At Week 16
Secondary	Number of Participants With Clinical Remission Over Time	Clinical remission is defined by 2-item PRO subs-cores of average worst daily abdominal pain (based on 11 point NRS ranging from 0 [no pain] to 10 [worst imaginable pain]); and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid).	Baseline up to Week 16
Secondary	Change From Baseline in Individual and Total Sign/Symptom Score Based on Participant Daily Electronic Diary (E-diary) Entries at Week 16	CD clinical signs and symptoms includes total stool frequency, rectal bleeding frequency, rectal urgency frequency, nausea severity, vomiting frequency, and rectal incontinence frequency.	Baseline and at Week 16
Secondary	Number of Participants With Endoscopic Healing at Week 16	Endoscopic healing is measured by SES-CD <=4 and at least 2-point reduction versus baseline and no sub-score >1 in any individual variable. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease.	At Week 16
Secondary	Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total (Absolute) Score at Weeks 8, 12 and 16	The IBDQ is a psychometrically validated PRO instrument for measuring the disease-specific health-related quality of life (HRQL) in participants with IBD, including CD. The IBDQ consists of 32 items, which are grouped into 4 domains and scored as: bowel function (10 to 70), systemic symptoms (5 to 35), emotional status (12 to 84), and social function (5 to 35). The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points is considered to indicate a clinically meaningful improvement.	Baseline, Weeks 8, 12 and 16
Secondary	Change From Baseline in Short Form-36 Health Survey (SF-36) Scores at Week 16	The SF-36, version 2 is a generic quality-of-life instrument that has been widely used to assess HRQL of participants. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.	Baseline, Week 16
Secondary	Number of Participants Based on Incidence of All-cause Hospitalizations	Incidence of all cause hospitalizations was planned to be assessed.	Baseline up to Week 32
Secondary	Number of Participants Based on Total Inpatient Days	Total inpatient days were planned to be assessed.	Baseline up to Week 32
Secondary	Number of Participants Based on Incidence of CD-related Surgeries and Other Surgical Procedures	Incidence of CD-related surgeries and other surgical procedures were planned to be recorded.	Baseline up to Week 32

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