Efficacy and Safety of Vedolizumab Subcutaneous (SC) as Maintenance Therapy in Crohn's Disease (CD)

NCT ID: NCT02611817

Last Updated: 2022-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 644 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-04
• Study Completion Date: 2019-08-06

Brief Summary

The purpose of this study is to assess the effect of vedolizumab subcutaneous (vedolizumab SC) as maintenance treatment in participants with moderately to severely active CD who achieved clinical response following administration of vedolizumab intravenous (vedolizumab IV) induction therapy.

Detailed Description

The drug being tested in this study is called vedolizumab SC. Vedolizumab SC is being tested to treat people who have moderate to severely active CD. This study will look at clinical remission, as well as enhanced clinical response and corticosteroid-free remission in participants with CD who receive vedolizumab SC maintenance therapy after having achieved a clinical response to vedolizumab IV induction therapy.

The study will enroll approximately 824 participants. All participants will enter a 6 week Induction Phase where they will be administered open-label vedolizumab IV 300 mg via IV infusion at Week 0 (Day 1) and Week 2 (Day 15), and will then be assessed for a clinical response at Week 6. Participants who achieve a clinical response at Week 6 will be randomly assigned to one of the two treatment groups:

• Vedolizumab SC 108 mg Maintenance Arm
• Placebo SC Maintenance Arm

Participants who do not achieve a clinical response will not be randomized into the Maintenance Period, and instead will receive a third infusion of vedolizumab IV 300 mg at Week 6.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 71 weeks. Participants will make multiple visits to the clinic, plus a final visit 18 weeks after last dose of study drug for a follow-up assessment. Participants will also participate in a long-term safety follow-up, by phone, at 6 months after the last dose of study drug.

Conditions

Crohn's Disease

Study Design

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

Study Groups

Vedolizumab SC 108 mg Maintenance Arm

Open-label Induction: vedolizumab IV 300 milligram (mg), infusion at Week 0 (Day 1) and Week 2 (Day 15)

Double-blind Maintenance: vedolizumab SC 108 mg injection once every 2 weeks (Q2W) starting at Week 6 up to Week 50

Group Type: EXPERIMENTAL

Vedolizumab SC 108 mg

Intervention Type: DRUG

Vedolizumab SC Injection.

Vedolizumab IV 300 mg

Intervention Type: DRUG

Vedolizumab IV Injection.

Placebo SC Maintenance Arm

Open-label Induction: vedolizumab IV 300 mg, infusion at Week 0 (Day 1) and Week 2 (Day 15)

Double-blind Maintenance: matching placebo to vedolizumab SC injection Q2W starting at Week 6 up to Week 50

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Vedolizumab placebo-matching SC injection.

Vedolizumab IV 300 mg

Intervention Type: DRUG

Vedolizumab IV Injection.

Interventions

Vedolizumab SC 108 mg

Vedolizumab SC Injection.

Intervention Type: DRUG

Placebo

Vedolizumab placebo-matching SC injection.

Intervention Type: DRUG

Vedolizumab IV 300 mg

Vedolizumab IV Injection.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of CD established at least 3 months prior to screening by clinical and endoscopic evidence corroborated by a histopathology report.

2. Moderately to severely active CD as determined by a CDAI score of 220 to 450 and 1 of the following:

• C-reactive protein (CRP) level greater than (>) 2.87 milligram per liter (mg/L) OR
• Ileocolonoscopy with photographic documentation of a minimum of 3 nonanastomotic ulcerations (each >0.5 centimeter [cm] in diameter) or 10 aphthous ulcerations (involving a minimum of 10 contiguous cm of intestine) consistent with CD OR
• Fecal calprotectin >250 microgram per gram (mcg/g) stool during the screening period in conjunction with computed tomography enterography (CTE), magnetic resonance enterography (MRE), contrast-enhanced small bowel radiography, or wireless capsule endoscopy revealing CD ulcerations (aphthae not sufficient).

3. CD involvement of the ileum and/or colon, at a minimum.

4. Inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or Tumor necrosis factor-alpha (TNF-α) antagonists.

Exclusion Criteria

1. Evidence of abdominal abscess at Screening.

2. Extensive colonic resection, subtotal or total colectomy.

3. History of >3 small bowel resections or diagnosis of short bowel syndrome.

4. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.

5. Prior exposure to investigational or approved non-biologic therapies (example, cyclosporine, tacrolimus, thalidomide, or tofacitinib) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer).

6. Prior exposure to any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of screening (whichever is longer).

7. Prior exposure to vedolizumab.

8. Surgical intervention for CD required at any time during the study.

9. History or evidence of adenomatous colonic polyps that have not been removed, or of colonic mucosal dysplasia.

10. Suspected or confirmed diagnosis of ulcerative colitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.

11. Active infections.

12. Chronic hepatitis B virus (HBV) or C (HCV) infection, tuberculosis (TB) (active or latent), or congenital or acquired immunodeficiency. HBV immune participants (that is, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included.

13. History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Arizona Arthritis & Rheumatology Research, PLLC

Phoenix, Arizona, United States

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, United States

Middlesex Gastroenterology Associates

Middletown, Connecticut, United States

Nature Coast Clinical Research, LLC

Inverness, Florida, United States

L & L Research Choices, Inc.

Miami, Florida, United States

Gastroenterology Group of Naples

Naples, Florida, United States

Shafran Gastroenterology Center

Winter Park, Florida, United States

Atlanta Gastroenterology Associates

Atlanta, Georgia, United States

Gastroenterology Associates of Central Georgia

Macon, Georgia, United States

Atlanta Gastroenterology Specialists, PC

Suwanee, Georgia, United States

Grand Teton Research Group, PLL

Idaho Falls, Idaho, United States

Rush University Medical Center

Chicago, Illinois, United States

Carle Foundation Hospital

Urbana, Illinois, United States

Cotton-O'Neil Clinical Research Center, Digestive Health

Topeka, Kansas, United States

Tri-State Gastroenterology Associates

Crestview Hills, Kentucky, United States

Gastroenterology Associates, LLC

Baton Rouge, Louisiana, United States

Louisiana Research Center, LLC

Shreveport, Louisiana, United States

Metropolitan Gastroenterology Group, PC, Chevy Chase Clinical Research

Chevy Chase, Maryland, United States

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, United States

Gastroenterology Associates of Western Michigan, P.L.C.

Wyoming, Michigan, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Ehrhardt Clinical Research, LLC

Belton, Missouri, United States

Long Island Clinical Research Associates

Great Neck, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Gastro-Enterology Research of Lima

Lima, Ohio, United States

Options Health Research

Tulsa, Oklahoma, United States

Gastroenterology Center of the MidSouth PC

Germantown, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

San Antonio Gastroenterology

San Antonio, Texas, United States

Allegiance Research Specialists, LLC

Milwaukee, Wisconsin, United States

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Tennyson Centre Day Hospital

Bedford Park, South Australia, Australia

Ballarat Base Hospital

Ballarat, Victoria, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

St John of God Subiaco Hospital

Subiaco, Western Australia, Australia

Imeldaziekenhuis

Bonheiden, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

AZ Groeninge - Kennedylaan

Kortrijk, , Belgium

ZNA Jan Palfijn

Merksem, , Belgium

AZ Delta

Roeselare, , Belgium

University Clinical Centre of the Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

University Clinical Hospital Mostar

Mostar, , Bosnia and Herzegovina

Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda

Goiânia, Goiás, Brazil

HUGG - Hospital Universitario Gaffree e Guinle

Rio de Janeiro, Rio Do Janeiro, Brazil

HUCFF-UFRJ - Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro

Rio de Janeiro, Rio Do Janeiro, Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu

Botucatu, São Paulo, Brazil

Faculdade de Medicina do ABC

Santo André, São Paulo, Brazil

Irmandade da Santa Casa da Misericordia de Santos

Santos, São Paulo, Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil

MHAT "Hadzhi Dimitar", OOD

Sliven, , Bulgaria

"City Clinic UMHAC" EOOD

Sofia, , Bulgaria

UMHAT "Sv. Ivan Rilski", EAD

Sofia, , Bulgaria

UMHAT 'Tsaritsa Yoanna - ISUL', EAD

Sofia, , Bulgaria

Fourth MHAT - Sofia EAD

Sofia, , Bulgaria

Zeidler Ledcor Centre - University of Alberta

Edmonton, Alberta, Canada

PerCuro Clinical Research Ltd.

Victoria, British Columbia, Canada

LHSC - University Hospital

London, Ontario, Canada

LHSC - Victoria Hospital

London, Ontario, Canada

Toronto Digestive Disease Associates, Inc.

Vaughan, Ontario, Canada

CCBR - Czech Brno, s.r.o..

Brno, , Czechia

Hepato-Gastroenterologie HK s.r.o.

Hradec Králové, , Czechia

A-SHINE s.r.o.

Pilsen, , Czechia

CCBR Czech Prague, s.r.o.

Prague, , Czechia

Axon Clinical s.r.o.

Prague, , Czechia

Odense Universitetshospital

Odense C, , Denmark

Regionshospitalet Silkeborg

Silkeborg, , Denmark

North Estonia Medical Centre Foundation

Tallinn, , Estonia

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Rhineland-Palatinate, Germany

EUGASTRO GmbH

Leipzig, Saxony, Germany

DRK Kliniken Berlin Westend

Berlin, , Germany

Krankenhaus Waldfriede e. V.

Berlin, , Germany

Obudai Egeszsegugyi Centrum Kft.

Budapest, , Hungary

Semmelweis Egyetem

Budapest, , Hungary

Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak

Budapest, , Hungary

Pannonia Maganorvosi Centrum

Budapest, , Hungary

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, , Hungary

Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz

Miskolc, , Hungary

Karolina Korhaz-Rendelointezet

Mosonmagyaróvár, , Hungary

Tolna Megyei Balassa Janos Korhaz

Szekszárd, , Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, , Hungary

HaEmek Medical Center

Afula, , Israel

Soroka University Medical Center

Beersheba, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Kaplan Medical Center

Rehovot, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

I.R.C.C.S Policlinico San Donato

San Donato Milanese (MI), Milano, Italy

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Azienda Ospedaliera Ospedale Cannizzaro

Catania, , Italy

Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)

Milan, , Italy

A.O.U. Policlinico di Modena

Modena, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Azienda Ospedaliera Vincenzo Cervello

Palermo, , Italy

Azienda Ospedaliera San Camillo Forlanini

Roma, , Italy

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Toho University Sakura Medical Center

Sakura-shi, Chiba, Japan

Fukuoka University Chikushi Hospital

Chikushino-shi, Fukuoka, Japan

Tokushukai Sapporo Tokushukai Hospital

Sapporo, Hokkaido, Japan

Sapporo-Kosei General Hospital

Sapporo, Hokkaido, Japan

Tokushukai Sapporo Higashi Tokushukai Hospital

Sapporo, Hokkaido, Japan

Hyogo College of Medicine Hospital

Nishinomiya-shi, Hyōgo, Japan

Iwate Medical University Hospital

Morioka, Iwate, Japan

Gokeikai Ofuna Chuo Hospital

Kamakura-shi, Kanagawa, Japan

Kinshukai Infusion Clinic

Osaka, Osaka, Japan

Saga University Hospital

Saga, Saga-ken, Japan

Hamamatsu South Hospital

Hamamatsu, Shizuoka, Japan

Kitasato University Kitasato Institute Hospital

Minatoku, Tokyo-To, Japan

JCHO Tokyo Yamate Medical Center

Shinjuku-ku, Tokyo-To, Japan

Wakayama Medical University Hospital

Wakayama, Wakayama, Japan

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

Vilnius University Hospital Santariskiu Clinic, Public Institution

Vilnius, , Lithuania

Morales Vargas Centro de Investigacion, S.C.

León, Guanajuato, Mexico

Centro de Investigacion Farmacologica del Bajio, S.C.

León, Guanajuato, Mexico

Instituto de Investigaciones Aplicadas a la Neurociencia A.C.

Durango, , Mexico

Sociedad de Metabolismo y Corazon S.C

Veracruz, , Mexico

Academisch Medisch Centrum

Amsterdam, , Netherlands

Albert Schweitzer Ziekenhuis, Dordwijk

Dordrecht, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

NZOZ Vitamed

Bydgoszcz, , Poland

Gabinet Endoskopii Przewodu Pokarmowego

Krakow, , Poland

SPZOZ Uniwersytecki Szpital Klin. nr 1 im.N.Barlickiego UM

Lodz, , Poland

Santa Familia Centrum Badan, Profilaktyki i Leczenia

Lodz, , Poland

GASTROMED Sp. z o.o.

Lublin, , Poland

Twoja Przychodnia-Szczecinskie Centrum Medyczne

Szczecin, , Poland

Centrum Zdrowia MDM

Warsaw, , Poland

Centralny Szpital Kliniczny MSW w Warszawie

Warsaw, , Poland

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, , Poland

Nzoz Vivamed

Warsaw, , Poland

LexMedica Osrodek Badan Klinicznych

Wroclaw, , Poland

Ars-Medica S.C Rybak Maria, Rybak Zbigniew

Wroclaw, , Poland

Spitalul Clinic Colentina

Bucharest, , Romania

Institutul Clinic Fundeni

Bucharest, , Romania

S.C Centrul de Gastroenterologie Dr. Goldis S.R.L

Timișoara, , Romania

Kazan State Medical University

Kazan', , Russia

TSBIH "Territorial Clinical Hospital"

Krasnoyarsk, , Russia

SBEIHPE Novosibirsk State Medical University

Novosibirsk, , Russia

FSBSI "Scientific and Research Institute of Physiology and Basic Medicine"

Novosibirsk, , Russia

BHI of Omsk region Clinical Oncology Dispensary

Omsk, , Russia

SBEI of HPE "Omsk SMA" SBEI HPE "Omsk State Medical University" of the MoH of the RF

Omsk, , Russia

SBEI HPE "Rostov State Medical University" of the MoH of the RF

Rostov-on-Don, , Russia

SPb SBIH "City Hospital of Saint Martyr Elizaveta"

Saint Petersburg, , Russia

LLC "RIAT SPb"

Saint Petersburg, , Russia

SPb SBIH "City Hospital # 40 of Kurortnyi region"

Sestroretsk, , Russia

SBIH of Yaroslavl region " Regional Clinical Hospital "

Yaroslavl, , Russia

Clinical Helth Centre Zvezdara

Belgrade, , Serbia

Military Medical Academy

Belgrade, , Serbia

Clinical Center Bezanijska kosa

Belgrade, , Serbia

Clinical Center Kragujevac

Kragujevac, , Serbia

Clinical Center of Vojvodina

Novi Sad, , Serbia

Fakultna nemocnica s poliklinikou F.D. Roosevelta

Banská Bystrica, , Slovakia

Univerzitna nemocnica Bratislava, Nemocnica Ruzinov

Bratislava, , Slovakia

Dr CCM Ziady Practice

Pretoria, Gauteng, South Africa

Dr JP Wright Practice

Cape Town, Western Cape, South Africa

Kyungpook National University Hospital

Daegu, , South Korea

Yeungnam University Hospital

Daegu, , South Korea

Kyung Hee University Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Kangbuk Samsung Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Karolinska Universitetssjukhuset - Solna

Stockholm, , Sweden

Mackay Memorial Hospital

Taipei, , Taiwan

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Haydarpasa Numune Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Marmara University Pendik Research and Training Hospital

Istanbul, , Turkey (Türkiye)

Kocaeli Derince Training and Research Hospital

Kocaeli, , Turkey (Türkiye)

Mersin University Medical Faculty

Mersin, , Turkey (Türkiye)

RCI Chernivtsi RCH Dep of Surgery HSEI of Ukr Bukovinian SMU

Chernivtsi, , Ukraine

SI Institute of Gastroenterology of NAMSU Dept of Stomach & Duodenum Diseases, D&ThN SI DMA of MoHU

Dnipro, , Ukraine

CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC

Kharkiv, , Ukraine

CI A.and O. Tropiny City Clinical Hospital

Kherson, , Ukraine

Kyiv CCH #12 Dept of Therapy O.O.Bogomolets NMU

Kyiv, , Ukraine

CI of Kyiv RC Kyiv Regional Clinical Hospital

Kyiv, , Ukraine

MI of Healthcare Kyiv RCH P.L. Shupyk NMA of PGE

Kyiv, , Ukraine

Communal City Clinical Hospital of Ambulance, Dept of Therapy #1 D.Halytskyi Lviv NMU

Lviv, , Ukraine

CI Odesa Regional Clinical Hospital

Odesa, , Ukraine

Ternopil University Hospital

Ternopil, , Ukraine

Private Small Enterprise Medical Center Pulse

Vinnytsia, , Ukraine

Vinnytsia RCH of Veterans of War Dept of Therapy#1 Vinnytsia M.I.Pyrogov NMU

Vinnytsia, , Ukraine

MCIC MC LLC Health Clinic

Vinnytsia, , Ukraine

CI City Hospital #1

Zaporizhzhia, , Ukraine

Royal Devon and Exeter Hospital (Wonford)

Exeter, Devon, United Kingdom

St George's Hospital

London, Greater London, United Kingdom

Whipps Cross University Hospital

London, Greater London, United Kingdom

Royal Shrewsbury Hospital

Shrewsbury, Shropshire, United Kingdom

University Hospital Coventry

Coventry, West Midlands, United Kingdom

Countries

United States; Australia; Belgium; Bosnia and Herzegovina; Brazil; Bulgaria; Canada; Czechia; Denmark; Estonia; Germany; Hungary; Israel; Italy; Japan; Lithuania; Mexico; Netherlands; Poland; Romania; Russia; Serbia; Slovakia; South Africa; South Korea; Sweden; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

D'Haens G, Baert F, Danese S, Kobayashi T, Loftus EV Jr, Sandborn WJ, Dornic Q, Lindner D, Kisfalvi K, Marins EG, Vermeire S. Efficacy of vedolizumab during intravenous induction therapy in ulcerative colitis and Crohn's disease: post hoc analysis of patient-reported outcomes from the VISIBLE 1 and 2 studies. Eur J Gastroenterol Hepatol. 2024 Apr 1;36(4):404-415. doi: 10.1097/MEG.0000000000002728. Epub 2024 Feb 21.

Reference Type: DERIVED

PMID: 38417060 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1168-0845

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015-000481-58

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL55774.056.16

Identifier Type: REGISTRY

Identifier Source: secondary_id

16/LO/0090

Identifier Type: REGISTRY

Identifier Source: secondary_id

MLN0002SC-3031CTID

Identifier Type: REGISTRY

Identifier Source: secondary_id

163300410A0045

Identifier Type: REGISTRY

Identifier Source: secondary_id

189748

Identifier Type: REGISTRY

Identifier Source: secondary_id

MOH_2017-01-05_000039

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-163386

Identifier Type: REGISTRY

Identifier Source: secondary_id

MLN0002SC-3031

Identifier Type: -

Identifier Source: org_study_id