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

NCT03559517 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: SHP647-305
• Study Type: interventional
• Target: 30
• Locations: 15 countries
• Sites: 132

Brief 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.

Conditions

Crohn's Disease

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (16)

• Number of Participants With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 16

  At Week 16

• Number of Participants With Enhanced Endoscopic Response at Week 16

  At Week 16

• Number of Participants With Clinical Remission Based on 2-item PRO With 4-point Scale for Abdominal Pain at Week 16

  At Week 16

• Number of Participants With Clinical Response Based on 2-item PRO With 2 Criteria at Week 16

  At Week 16

• Number of Participants With Clinical Remission Based on 2-Item PRO With Endoscopic Response at Week 16

  At Week 16

Study Arms (3)

Ontamalimab 25 mg

EXPERIMENTAL

Participants will receive 25 mg of ontamalimab subcutaneous injection using a prefilled syringe on Week 0/Day 1, Week 4, Week 8, and Week 12.

Biological: Ontamalimab

Ontamalimab 75 mg

EXPERIMENTAL

Participants will receive 75 mg of ontamalimab subcutaneous injection using a prefilled syringe on Week 0/Day 1, Week 4, Week 8, and Week 12.

Biological: Ontamalimab

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching with ontamalimab subcutaneous injection using a prefilled syringe on Week 0/Day 1, Week 4, Week 8, and Week 12.

Other: Placebo

Interventions

Ontamalimab BIOLOGICAL

Subcutaneous injection of ontamalimab will be administered using a prefilled syringe.

Also known as: PF-00547659, SHP647

Ontamalimab 25 mg; Ontamalimab 75 mg

Placebo OTHER

Subcutaneous injection of placebo matched with ontamalimab will be administered using a prefilled syringe.

Placebo

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• CDAI score between 220 and 450 (inclusive) AND
• 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:
• A biopsy report in which the description of the histological findings is consistent with the CD diagnosis AND
• 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 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Shire: lead

Study Sites (138)

CATS Research Center - University of Arizona

Tucson, Arizona, 85724, United States

Location

Atria Clinical Research - Clinedge - PPDS

Little Rock, Arkansas, 72209, United States

Location

OM Research LLC - Lancaster - ClinEdge - PPDS

Lancaster, California, 93534, United States

Location

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

Peak Gastroenterology Associates

Colorado Springs, Colorado, 80903, United States

Location

Asthma and Allergy Associates PC - CRN - PPDS

Colorado Springs, Colorado, 80907, United States

Location

Advanced Clinical Research Network

Miami, Florida, 33176, United States

Location

Gastroenterology Group of Naples

Naples, Florida, 34102, United States

Location

Omega Research Consultants LLC - Clinedge - PPDS

Orlando, Florida, 32810, United States

Location

East Coast Institute for Research, LLC

Saint Augustine, Florida, 32086, United States

Location

Laporte County Institute For Clinical Research

Michigan City, Indiana, 46360, United States

Location

Clinical Trials of SWLA LLC

Lake Charles, Louisiana, 70601, United States

Location

Louisiana Research Center LLC

Shreveport, Louisiana, 71103, United States

Location

New York Total Medical Care PC

Brooklyn, New York, 11215, United States

Location

Piedmont Healthcare

Statesville, North Carolina, 28625, United States

Location

Consultants For Clinical Research Inc

Cincinnati, Ohio, 45219, United States

Location

Consultants For Clinical Research Inc

Cincinnati, Ohio, 45249, United States

Location

Consultants For Clinical Research Inc

Fairfield, Ohio, 45014, United States

Location

Digestive Disease Associates

Wyomissing, Pennsylvania, 19610, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Advanced Gastroenterology-Union City

Union City, Tennessee, 38261, United States

Location

Inquest Clinical Research/Coastal Gastroenterology Associates, PA - TDDC - PPDS

Baytown, Texas, 77521, United States

Location

Northside Gastroenterology

Cypress, Texas, 77429, United States

Location

HP Clinical Research

Bountiful, Utah, 84010, United States

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Mater Hospital Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

St Vincents Hospital Melbourne - PPDS

Melbourne, Victoria, 3065, Australia

Location

LKH-Universitätsklinikum Klinikum Graz

Graz, Styria, 8036, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Vienna, Vienna, A-1090, Austria

Location

Salzburger Landeskliniken

Salzburg, 5020, Austria

Location

Medizinische Universitat Wien (Medical University of Vienna)

Vienna, 1090, Austria

Location

University Hospital Center Zagreb

Zagreb, City of Zagreb, 10000, Croatia

Location

Opca bolnica Bjelovar

Bjelovar, 43000, Croatia

Location

Clinical Hospital Centre Osijek

Osijek, 31000, Croatia

Location

General Hospital Virovitica

Virovitica, 33000, Croatia

Location

Universitätsklinikum der RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Uniklinik Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Gastro Campus Research GbR

Münster, North Rhine-Westphalia, 48159, Germany

Location

Universitatsklinikum Schleswig-Holstein

Kiel, Schleswig-Holstein, 24105, Germany

Location

Universitatsklinikum Jena

Jena, Thuringia, 07747, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Gastroenterologische Facharztpraxis am Mexikoplatz

Berlin-Zehlendorf, 14163, Germany

Location

Sana Klinikum Biberach

Biberach an der Riss, 88400, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60596, Germany

Location

Klinikum rechts der Isa der Technischen Universitaet Muenchen

Munich, 81675, Germany

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Hadassah Medical Center - PPDS

Jerusalem, 91120, Israel

Location

Galilee Medical Center

Nahariya, 22100, Israel

Location

Baruch Padeh Poriya Medical Center

Tiberias, 15208, Israel

Location

Azienda Ospedaliera Mater Domini Di Catanzaro

Catanzaro, Calabria, 88100, Italy

Location

Azienda Ospedaliero Universitaria Di Modena Policlinico

Modena, Emilia-Romagna, 41100, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50134, Italy

Location

Ospedale Sacro Cuore Don Calabria

Negrar, Veneto, 37024, Italy

Location

A.O.U. Maggiore della Carità

Novara, 28100, Italy

Location

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, 27100, Italy

Location

La Sapienza-Università di Roma-Policlinico Umberto I

Roma, 00161, Italy

Location

Istituto Clinico Humanitas

Rozzano (MI), 20089, Italy

Location

Ospedale Casa Sollievo Della Sofferenza IRCCS

San Giovanni Rotondo, 71013, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Sapporo Tokushukai Hospital

Sapporo, Hokkaidô, 004-0041, Japan

Location

Jikei University Hospital

Minato-ku, Tokyo, 105-8471, Japan

Location

Ome Municipal General Hospital

Ōme, Tokyo, 198-0042, Japan

Location

Hidaka Coloproctology Clinic

Kurume-shi, 839-0809, Japan

Location

Aichi Medical University Hospital

Nagakute, 480-1195, Japan

Location

Nishinomiya Municipal Central Hospital

Nishinomiya, 663-8014, Japan

Location

Onomichi General Hospital

Onomichi, Japan

Location

Shiga University of Medical Science Hospital

Ōtsu, 520-2192, Japan

Location

Sapporo Higashi Tokushukai Hospital

Sapporo, 065-0033, Japan

Location

Colo-Proctology Center Matsushima Clinic

Yokohama, 220-0045, Japan

Location

Vilnius University Hospital Santaros Klinikos

Vilnius, LT- 08661, Lithuania

Location

Vilnius City Clinical Hospital

Vilnius, LT-10207, Lithuania

Location

ETZ-Elisabeth

Tilburg, North Brabant, 5022 GC, Netherlands

Location

NWZ, location Alkmaar

Den Helder, North Holland, 1782 GZ, Netherlands

Location

Academisch Medisch Centrum Amsterdam

Amsterdam, 1105 AZ, Netherlands

Location

Vitamed Galaj i Cichomski sp.j.

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-079, Poland

Location

Gastromed Kopon Zmudzinski i Wspolnicy Sp.j.Specjalistyczne Centrum Gastrologii i Endoskopii Specj

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Centrum Diagnostyczno - Lecznicze Barska sp. z o.o.

Włocławek, Kuyavian-Pomeranian Voivodeship, 87-800, Poland

Location

Melita Medical

Wroclaw, Lower Silesian Voivodeship, 50-449, Poland

Location

Lexmedica

Wroclaw, Lower Silesian Voivodeship, 53-114, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej CENTRUM MEDYCZNE Szpital Swietej Rodziny

Lódz, Lódzkie, 90-302, Poland

Location

Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Sp. J.

Lódz, Lódzkie, 90-647, Poland

Location

Centrum Medyczne Warszawa - PRATIA - PPDS

Warsaw, Masovian Voivodeship, 00-660, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED

Warsaw, Masovian Voivodeship, 03-580, Poland

Location

Miedzyleski Szpital Specjalistyczny w Warszawie

Warsaw, Masovian Voivodeship, 04-749, Poland

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, Podlaskie Voivodeship, 15-276, Poland

Location

Endoskopia Sp. z o.o.

Sopot, Pomeranian Voivodeship, 81-756, Poland

Location

Twoja Przychodnia - Szczecińskie Centrum Medyczne

Szczecin, West Pomeranian Voivodeship, 71-434, Poland

Location

Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

Centrum Medyczne Czestochowa - PRATIA - PPDS

Częstochowa, 42-200, Poland

Location

Centrum Medyczne Gdynia - PRATIA - PPDS

Gdynia, 81-338, Poland

Location

BioVirtus Centrum Medyczne

Józefów, 05-410, Poland

Location

NZOZ All Medicus

Katowice, 40-659, Poland

Location

Med Gastr Sp.z.o.o Sp.k

Lodz, 91-034, Poland

Location

Instytut Centrum Zdrowia Matki Polki

Lodz, 93-338, Poland

Location

Twoja Przychodnia - Centrum Medyczne Nowa Sol

Nowa Sól, 67-100, Poland

Location

Clinical Research Center Spółka z Ograniczoną Odpowiedzialnością, Medic-R Spółka Komandytowa

Poznan, 60-856, Poland

Location

Korczowski Bartosz, Gabinet Lekarski

Rzeszów, 35-302, Poland

Location

Sonomed Sp. z o.o.

Szczecin, 70-361, Poland

Location

Centrum Zdrowia M D M

Warsaw, 00-635, Poland

Location

Centralny Szpital Kliniczny MSW

Warsaw, 02-507, Poland

Location

Samodzielny Publiczny Szpital Wojewodzki im. Papieza Jana Pawla II

Zamość, 22-400, Poland

Location

Szpital Specjalistyczny sw Lukasza - Oddzial Gastroenterologii

Gmina Końskie, Świętokrzyskie Voivodeship, 26-200, Poland

Location

Sana Monitoring SRL

Bucharest, București, 011025, Romania

Location

Cluj-Napoca Emergency Clinical County Hospital

Cluj-Napoca, Cluj, 400006, Romania

Location

Dr.Carol Davila Emergency University Central Military Hospital

Bucharest, 010825, Romania

Location

Colentina Clinical Hospital

Bucharest, 020125, Romania

Location

Prof. Dr. Matei Bals Institute of Infectious Diseases

Bucharest, 021105, Romania

Location

Fundeni Clinical Institute

Bucharest, 022328, Romania

Location

Centrul Medical Hifu Terramed Conformal S.R.L.

Bucharest, 031864, Romania

Location

Emergency University Hospital

Bucharest, 050098, Romania

Location

Affidea Romania SRL

Constanța, RO-900591, Romania

Location

Gastromedica SRL

Iași, 700506, Romania

Location

Dr. Tirnaveanu Amelita Private Practice

Oradea, 410066, Romania

Location

Dr. Goldis Gastroenterology Center SRL

Timișoara, 300002, Romania

Location

Rostov State Medical University

Rostov-on-Don, 344091, Russia

Location

St. Elizabeth Municipal Clinical Hospital

Saint Petersburg, 195067, Russia

Location

Russian Medical Military Academy n.a. S.M. Kirov

Saint Petersburg, Russia

Location

Medical University Reaviz

Samara, 443011, Russia

Location

Private Healthcare Institution Clinical Hospital RZD-Medicina of Samara city

Samara, 443029, Russia

Location

SHI Regional Clinical Hospital

Saratov, 410012, Russia

Location

Clinical Hospital Center ''Bezanijska Kosa''

Belgrade, 11080, Serbia

Location

University Clinical Center Nis

Niš, 18000, Serbia

Location

General Hospital Vrsac

Vršac, 26300, Serbia

Location

Clinical Hospital Center Zemun

Zemun, Serbia

Location

University Clinical Center Kragujevac

Kragujevac, Šumadijski Okrug, 34000, Serbia

Location

CLINRESCO, ARWYP Medical Suites

Johannesburg, Gauteng, 1619, South Africa

Location

Dr. J Breedt

Pretoria, Gauteng, 0084, South Africa

Location

Emmed Research

Pretoria, Gauteng, 0084, South Africa

Location

Dr JP Wright

Claremont, Western Cape, 7708, South Africa

Location

North Tyneside General Hospital

North Shields, Northumberland, NE29 8NH, United Kingdom

Location

Aberdeen Royal Infirmary - PPDS

Aberdeen, AB25 2ZN, United Kingdom

Location

Royal Gwent Hospital - PPDS

Newport, NP20 2UB, United Kingdom

Location

New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (1)

• Vermeire S, Danese S, Sandborn WJ, Schreiber S, Hanauer S, D'Haens G, Nagy P, Thakur M, Bliss C, Cataldi F, Goetsch M, Gorelick KJ, Reinisch W. Efficacy and Safety of the Anti-mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn's Disease. J Crohns Colitis. 2024 May 31;18(5):708-719. doi: 10.1093/ecco-jcc/jjad199.

  PMID: 38096402 DERIVED

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Crohn Disease

Interventions

ontamalimab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

The study was terminated as the sponsor discontinued the ontamalimab clinical trial program in ulcerative colitis and CD for reasons unrelated to safety.

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@takeda.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: June 18, 2018
• Study Start: August 29, 2018
• Primary Completion: July 7, 2020
• Study Completion: October 8, 2020
• Last Updated: April 29, 2021
• Results First Posted: April 29, 2021

Record last verified: 2021-04

Locations

JP (10); NL (3); RO (12); LI (2); AU (4); IL (4); RU (6); GB (4); IT (10); US (25); DE (10); SE (5); ZA (4); PL (29); CR (4)