Efficacy and Safety Study of Ontamalimab as Induction Therapy in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 306)

NCT03566823 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: SHP647-306
• Study Type: interventional
• Target: 34
• Locations: 19 countries
• Sites: 143

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: SHP647, PF-00547659

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 (145)

Arizona Digestive Health Mesa - East

Mesa, Arizona, 85206, United States

Location

Elite Clinical Studies - Phoenix - Clinedge - PPDS

Phoenix, Arizona, 85018, United States

Location

Advanced Research Center

Anaheim, California, 92805, United States

Location

Kindred Medical Institute for Clinical Trials, LLC

Corona, California, 92879, United States

Location

Alliance Clinical Research-(Vestavia Hills)

Poway, California, 92064, United States

Location

Care Access Research, San Pablo

San Pablo, California, 94806, United States

Location

Renaissance Research Medical Group, INC

Cape Coral, Florida, 33991, United States

Location

Gastro Florida

Clearwater, Florida, 33756, United States

Location

Alliance Medical Research LLC

Coral Springs, Florida, 33071, United States

Location

SIH Research

Kissimmee, Florida, 34741, United States

Location

Hi Tech and Global Research, LLc

Miami, Florida, 33135, United States

Location

Sanchez Clinical Research, Inc

Miami, Florida, 33157, United States

Location

Crystal Biomedical Research

Miami Lakes, Florida, 33065, United States

Location

Pharma Research International Inc

Naples, Florida, 34110, United States

Location

Bayside Clinical Research - New Port Richey

New Port Richey, Florida, 34655, United States

Location

Accel Research Sites - St. Petersburg - ERN - PPDS

Pinellas Park, Florida, 33781, United States

Location

DBC Research

Tamarac, Florida, 33321, United States

Location

Infinite Clinical Trials

Atlanta, Georgia, 30349, United States

Location

Atlanta Center For Gastroenterology PC

Decatur, Georgia, 30033, United States

Location

Atlanta Gastroenterology Specialists, PC

Suwanee, Georgia, 30024, United States

Location

Loretto Hospital

Chicago, Illinois, 60644, United States

Location

IL Gastroenterology Group

Gurnee, Illinois, 60031, United States

Location

Cotton O'Neil Clinical Research Center

Topeka, Kansas, 66606, United States

Location

Gastroenterology Associates of Hazard

Hazard, Kentucky, 41701, United States

Location

CroNOLA, LLC.

Houma, Louisiana, 70360, United States

Location

DelRicht Clinical Research, LLC - ClinEdge - PPDS

New Orleans, Louisiana, 70115, United States

Location

Commonwealth Clinical Studies LLC

Brockton, Massachusetts, 02302, United States

Location

Winchester Gastroenterology Associates

Winchester, Massachusetts, 22601, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Clinical Research Institute of Michigan

Chesterfield, Michigan, 48047, United States

Location

National Clinical, LLC

Hamtramck, Michigan, 48212, United States

Location

Gastroenterology Associates of Western Michigan, PLC

Wyoming, Michigan, 49519, United States

Location

Mayo Clinic Health System - PPDS

Duluth, Minnesota, 55805, United States

Location

Minnesota Gastroenterology PA

Plymouth, Minnesota, 55446, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Advanced Biomedical Research of America

Las Vegas, Nevada, 89123, United States

Location

Encompass Care

North Las Vegas, Nevada, 89086, United States

Location

NYU Langone Long Island Clinical Research Associates

Great Neck, New York, 11021, United States

Location

Southtowns Gastroenterology, PLLC

Orchard Park, New York, 14127, United States

Location

Penn State Hershey Medical Group

State College, Pennsylvania, 16803, United States

Location

Digestive Health Associates of Texas, P.A.dba DHAT Research Institute

Garland, Texas, 75044, United States

Location

Precision Research Institute, LLC

Houston, Texas, 77039, United States

Location

Biopharma Informatic Inc.

Houston, Texas, 77043, United States

Location

Southwest Clinical Trials

Houston, Texas, 77074, United States

Location

BI Research Center

Houston, Texas, 77084, United States

Location

Southern Star Research Institute LLC

San Antonio, Texas, 78229, United States

Location

Mid Atlantic Health Specialists

Galax, Virginia, 24333, United States

Location

Fundación Favaloro

Buenos Aires, C1093AAS, Argentina

Location

Hospital Privado Centro Médico de Córdoba

Córdoba, Argentina

Location

UZ Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

AZ Groeninge

Kortrijk, West-Vlaanderen, 8500, Belgium

Location

CHU Mouscron

Mouscron, 7700, Belgium

Location

Clinical Center Banja Luka

Banja Luka, 78000, Bosnia and Herzegovina

Location

Acibadem City Clinic University Multiprofile Hospital for Active Treatment EOOD

Sofia, Sofia-Grad, 1784, Bulgaria

Location

Multiprofile Hospital for Active Treatment Eurohospital

Plovdiv, 4000, Bulgaria

Location

Second Multiprofile Hospital for Active Treatment Sofia

Sofia, 1202, Bulgaria

Location

Diagnostic and Consulting Center Aleksandrovska EOOD

Sofia, 1431, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD

Sofia, 1431, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD

Sofia, 1527, Bulgaria

Location

Medical Center Excelsior OOD - PPDS

Sofia, 1632, Bulgaria

Location

Medical Center Convex EOOD

Sofia, 1680, Bulgaria

Location

Diagnostic Consultative Centre Mladost - M OOD

Varna, 9000, Bulgaria

Location

Fundación Valle Del Lili

Cali, Valle del Cauca Department, 760026, Colombia

Location

IPS Centro Médico Julián Coronel S.A.S. - PPDS

Cali, Valle del Cauca Department, 760035, Colombia

Location

OÜ LV Venter

Pärnu, 80010, Estonia

Location

West Tallinn Central Hospital

Tallinn, 10617, Estonia

Location

Ippokrateio General Hospital of Athens

Athens, Attica, 11527, Greece

Location

University General Hospital of Heraklion

Heraklion, 71110, Greece

Location

Iatriko Palaiou Falirou

Paliao Faliro, 17562, Greece

Location

University General Hospital of Patras

Pátrai, 26504, Greece

Location

Euromedica - PPDS

Thessaloniki, 54645, Greece

Location

Bekes Megyei Kozponti Korhaz

Békéscsaba, 5600, Hungary

Location

Magyar Honvédség Egészségügyi Központ

Budapest, 1062, Hungary

Location

Pannónia Magánorvosi Centrum Kft

Budapest, 1135, Hungary

Location

ENDOMEDIX Kft.

Budapest, 1139, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Mohacsi Korhaz

Mohács, 7700, Hungary

Location

Tolna Megyei Balassa János Kórház

Szekszárd, 7100, Hungary

Location

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, 8000, Hungary

Location

St Vincent's University Hospital

Dublin, 4, Ireland

Location

Sapporo Medical University Hospital

Sapporo, Hokkaidô, 060-8543, Japan

Location

Medical Corporation Aoyama Clinic

Kobe, Hyôgo, 650-0015, Japan

Location

Hyogo College of Medicine

Nishinomiya-shi, Hyôgo, 663-8501, Japan

Location

Kunimoto Hospital

Asahikawa, 070-0061, Japan

Location

Chiinkai Dojima General & Gastroenterology Clinic

Osaka, 530-0003, Japan

Location

Kinshukai Infusion Clinic

Osaka, 530-0011, Japan

Location

Yodogawa Christian Hospital

Osaka, 533-0024, Japan

Location

Toho University Sakura Medical Center

Sakura, 285-8741, Japan

Location

Dokkyo Medical University Hospital

Shimotsuga-gun, 321-0293, Japan

Location

Nihonbashi Egawa Clinic

Tokyo, 103-0028, Japan

Location

Ishida Clinic of IBD and Gastroenterology

Ōita, Ôita, 870-0823, Japan

Location

Al Zahraa University Hospital

Beirut, Lebanon

Location

Hammoud Hospital University Medical Center

Saida, Lebanon

Location

Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.

Zapopan, Jalisco, 45030, Mexico

Location

Health Pharma Professional Research S.A de C.V.

Mexico City, Mexico City, 03810, Mexico

Location

Clinica de Higado y Gastroenterologia Integral, S.C.

Cuernavaca, Morelos, 62170, Mexico

Location

JM Research S.C

Cuernavaca, Morelos, 62290, Mexico

Location

Accelerium, S. de R.L. de C.V.

Monterrey, Nuevo León, 64000, Mexico

Location

Unidad de Atencion Medica e Investigacion en Salud

Mérida, Yucatán, 97000, Mexico

Location

Centro de Investigacion Clinica Acelerada, S.C.

Distrito Federal, 07020, Mexico

Location

Instituto de Investigaciones Aplicadas a la Neurociencia A.C.

Durango, 34000, Mexico

Location

Dunedin Hospital

Dunedin, South Island, 9016, New Zealand

Location

Wellington Hospital

Newtown, Wellington Region, 6021, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Hospital da Luz

Lisbon, Lisbon District, 1500-650, Portugal

Location

Hospital Senhora da Oliveira - Guimaraes, E.P.E

Guimarães, 4835-044, Portugal

Location

Centro Hospitalar do Algarve - Hospital de Portimao

Portimão, 8500-338, Portugal

Location

KM Management, spol. s r.o.

Nitra, 949 01, Slovakia

Location

Gastro LM, s.r.o.

Prešov, 080 01, Slovakia

Location

CHA Bundang Medical Center, CHA University

Seongnam, Gyeonggido, 13496, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggido, 16247, South Korea

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Kyungpook National University Chilgok Hospital

Daegu, 702-210, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Inje University Seoul Paik Hospital

Seoul, 04551, South Korea

Location

Yonsei University Wonju Severance Christian Hospital

Wonju-si, Gangwon-do, 26426, South Korea

Location

C.H. Regional Reina Sofia - PPDS

Córdoba, Córdoba, 14004, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, 28942, Spain

Location

Hospital Universitario La Paz - PPDS

Madrid, Madrid, Communidad Delaware, 28046, Spain

Location

CHUVI - H.U. Alvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Centro Medico Teknon - Grupo Quironsalud

Barcelona, 8022, Spain

Location

Hospital Universitario Juan Ramon Jimenez

Huelva, 21005, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi

Istanbul, 34098, Turkey (Türkiye)

Location

Mersin University Medical Faculty

Mersin, 33169, Turkey (Türkiye)

Location

Regional Municipal Non-profit Enterprise "Chernivtsi Regional Clinical Hospital"

Chernivtsi, Chernivtsi Oblast, 58001, Ukraine

Location

Municipal Nonprofit Enterprise CCH #2 n.a. prof. O.O. Shalimov of Kharkiv City Council

Kharkiv, Kharkivs’ka Oblast’, 61037, Ukraine

Location

Municipal Non-profit Enterprise of Kyiv Regional Council Kyiv Regional Clinical Hospital

Kyiv, Kyïv, 04107, Ukraine

Location

LLC Medical Center Family Medicine Clinic

Dnipro, 49038, Ukraine

Location

Municipal Nonprofit Enterprise of Kharkiv Regional Council Regional Clinical Hospital

Kharkiv, 61058, Ukraine

Location

Municipal Non-profit Enterprise Kherson City Clinical Hospital named after Ye.Ye. Karabelesh

Kherson, 73000, Ukraine

Location

Medical Center of LLC Medical Clinic Blagomed

Kyiv, 01023, Ukraine

Location

Medical Center OK!Clinic+LLC International Institute of Clinical Research

Kyiv, 02091, Ukraine

Location

Medical Center of LLC Medical Center Dopomoga-Plus

Kyiv, 02132, Ukraine

Location

Communal Non-profit Enterprise of Kyiv Regional Council Kyiv Regional Hospital

Kyiv, 04073, Ukraine

Location

Municipal Nonprofit Enterprise Lviv Clinical Emergency Care Hospital

Lviv, 79059, Ukraine

Location

Communal Non-Commercial Enterprise "Vinnytsia City Clinical Hospital No1"

Vinnytsia, 21029, Ukraine

Location

MNPE City Hospital No. 6 of Zaporizhzhia City Council

Zaporizhzhia, 69035, Ukraine

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 25, 2018
• Study Start: July 17, 2018
• Primary Completion: August 18, 2020
• Study Completion: August 18, 2020
• Last Updated: May 11, 2021
• Results First Posted: May 11, 2021

Record last verified: 2021-04

Locations

ME (8); BU (9); AR (2); GR (5); BO (1); IE (1); SL (2); TU (2); LE (2); HU (8); JP (11); CO (2); KR (11); UA (13); ES (9); NZ (3); PT (3); US (48); BE (3)