Efficacy and Safety of Vedolizumab Subcutaneously (SC) as Maintenance Therapy in Ulcerative Colitis

NCT ID: NCT02611830

Last Updated: 2022-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 383 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-18
• Study Completion Date: 2018-08-21

Brief Summary

The purpose of this study is to assess the effect of vedolizumab subcutaneous (vedolizumab SC) maintenance treatment on clinical remission at Week 52 in participants with moderately to severely active ulcerative colitis (UC) 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 subcutaneous (vedolizumab SC). Vedolizumab SC is being tested to treat people who have moderate to severely active ulcerative colitis. This study will look at clinical remission as well as mucosal healing, durable clinical response, durable clinical remission, and corticosteroid free remission in participants with UC who receive vedolizumab SC maintenance therapy after having achieved a clinical response to vedolizumab IV induction therapy.

The study enrolled 383 patients. All participants will enter into a 6-week Induction Phase where they will be administered open-label vedolizumab IV 300 mg via intravenous infusion (IV) 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 three treatment groups:

Vedolizumab SC 108 mg Q2W and Placebo IV Q8W Vedolizumab IV 300 mg Q8W and Placebo SC Q2W Placebo SC Q2W and Placebo IV Q8W

Participants who do not achieve a clinical response at Week 6 will not be randomized in to the Maintenance Period, and 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 (up to 4 weeks of screening, 52 weeks of treatment and 18 weeks of safety follow-up). 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.

After the Week 52 assessments, participants meeting protocol-defined criteria were eligible to enroll in Study MLN0002SC-3030 (NCT02620046; Long-term Safety) to receive open-label vedolizumab treatment. Participants who withdrew early (prior to Week 52) due to sustained nonresponse, disease worsening, or the need for rescue medications may also have been eligible for Study MLN0002SC-3030. Participants who did not enroll into Study MLN0002SC-3030 were to complete a final on-study safety assessment at Week 68 (or final safety visit 18 weeks after the last dose) in the Maintenance Phase of Study MLN0002SC-3027.

Conditions

Colitis, Ulcerative

Study Design

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

Study Groups

Maintenance Phase: Induction IV + Vedolizumab 108 mg SC

Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab SC in maintenance phase. Vedolizumab SC, 108 mg, injection, Q2W and placebo-matching IV infusions, Q8W, starting at Week 6 up to approximately Week 50.

Group Type: EXPERIMENTAL

Vedolizumab 300 mg IV

Intervention Type: DRUG

Vedolizumab intravenous infusion

Placebo IV

Intervention Type: DRUG

Vedolizumab intravenous infusion placebo

Vedolizumab 108 mg SC

Intervention Type: DRUG

Vedolizumab subcutaneous injection

Maintenance Phase: Induction IV + Vedolizumab 300 mg IV

Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab IV in maintenance phase. Vedolizumab 300 mg, IV infusion, Q8W and placebo-matching SC injection, Q2W starting at Week 6 up to approximately Week 50.

Group Type: EXPERIMENTAL

Vedolizumab 300 mg IV

Intervention Type: DRUG

Vedolizumab intravenous infusion

Placebo SC

Intervention Type: DRUG

Vedolizumab subcutaneous injection placebo

Maintenance Phase: Induction IV + Placebo

Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase. Placebo-matching subcutaneous (SC) injections, once every 2 weeks (Q2W) and placebo-matching IV infusions, once every 8 weeks (Q8W) starting at Week 6 up to approximately Week 50.

Group Type: EXPERIMENTAL

Vedolizumab 300 mg IV

Intervention Type: DRUG

Vedolizumab intravenous infusion

Placebo IV

Intervention Type: DRUG

Vedolizumab intravenous infusion placebo

Placebo SC

Intervention Type: DRUG

Vedolizumab subcutaneous injection placebo

Interventions

Vedolizumab 300 mg IV

Vedolizumab intravenous infusion

Intervention Type: DRUG

Placebo IV

Vedolizumab intravenous infusion placebo

Intervention Type: DRUG

Vedolizumab 108 mg SC

Vedolizumab subcutaneous injection

Intervention Type: DRUG

Placebo SC

Vedolizumab subcutaneous injection placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of ulcerative colitis (UC) established at least 6 months prior to screening, by clinical and endoscopic evidence and corroborated by a histopathology report.

2. Moderately to severely active UC as determined by a complete Mayo score of 6-12 (with an endoscopic subscore ≥2)

3. Evidence of UC extending proximal to the rectum (≥15 cm of involved colon).

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 or toxic megacolon at the initial Screening Visit.

2. Extensive colonic resection, subtotal or total colectomy.

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

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

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

6. Prior exposure to vedolizumab

7. Surgical intervention for UC required at any time during the study.

8. History or evidence of adenomatous colonic polyps that have not been removed or has a history or evidence of colonic mucosal dysplasia.

9. Suspected or confirmed diagnosis of Crohn's entercolitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.

10. Active infections

11. Chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection, HIV or tuberculosis (active or latent), identified congenital or acquired immunodeficiency. HBV immune participants (ie, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included.

12. History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating 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

Arkansas Primary Care Clinic, PA

Little Rock, Arkansas, United States

Rocky Mountain Clinical Research, LLC

Wheat Ridge, Colorado, United States

Middlesex Gastroenterology Associates

Middletown, Connecticut, United States

Nature Coast Clinical Research, LLC

Inverness, Florida, United States

Florida Center for Gastroenterology

Largo, 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

Cotton-O'Neil Clinical Research Center, Digestive Health

Topeka, Kansas, United States

Tri-State Gastroenterology Associates

Crestview Hills, Kentucky, United States

Research Concierge, LLC

Owensboro, Kentucky, United States

Gastroenterology Associates, LLC

Baton Rouge, 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

Ehrhardt Clinical Research, LLC

Belton, Missouri, United States

Long Island Clinical Research Associates

Great Neck, New York, United States

Premier Medical Group of the Hudson Valley, PC

Poughkeepsie, New York, United States

Dayton Gastroenterology, Inc

Dayton, Ohio, United States

Options Health Research

Tulsa, Oklahoma, United States

Gastro One

Germantown, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Tyler Research Institute, LLC

Tyler, Texas, United States

Gastroenterology Associates of Tidewater

Chesapeake, Virginia, United States

Virginia Mason Seattle Main Clinic

Seattle, Washington, United States

Expertia S.A- Mautalen Salud e Investigacion

Ciudad Autonoma Buenos Aires, , Argentina

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Clinique Saint-Pierre

Ottignies, , Belgium

AZ Delta

Roeselare, , Belgium

University Clinical Centre of the Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda

Goiânia, Goiás, Brazil

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

Rio de Janeiro, Rio Do Janeiro, 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

MHAT 'Avis Medica' OOD

Pleven, , Bulgaria

MHAT - Silistra AD

Silistra, , Bulgaria

MHAT "Hadzhi Dimitar", OOD

Sliven, , Bulgaria

Second MHAT - Sofia AD

Sofia, , Bulgaria

"City Clinic UMHAC" EOOD

Sofia, , Bulgaria

UMHAT "Sv. Ivan Rilski", EAD

Sofia, , Bulgaria

UMHAT 'Tsaritsa Yoanna - ISUL', EAD

Sofia, , Bulgaria

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD

Stara Zagora, , Bulgaria

London Health Science Centre

London, Ontario, Canada

LHSC - Victoria Hospital

London, Ontario, Canada

Toronto Digestive Disease Associates, Inc.

Vaughan, Ontario, Canada

Clinical Hospital Centre Osijek

Osijek, , Croatia

Clinical Hospital Centre Rijeka

Rijeka, , Croatia

Clinical Hospital Centre Zagreb

Zagreb, , Croatia

Clinical Hospital Dubrava

Zagreb, , Croatia

Ccbr-Synarc A/S

Brno, , Czechia

Hepato-Gastroenterologie HK, s.r.o.

Hradec Králové, , Czechia

A-SHINE s.r.o.

Pilsen, , Czechia

Ccbr-Synarc A/S

Prague, , Czechia

Axon Clinical, s.r.o.

Prague, , Czechia

Odense Universitetshospital

Odense C, , Denmark

West Tallinn Central Hospital

Tallinn, , Estonia

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

EUGASTRO GmbH

Leipzig, Saxony, Germany

Krankenhaus Waldfriede e. V.

Berlin, , Germany

Obudai Egeszsegugyi Centrum Kft.

Budapest, , Hungary

Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak

Budapest, , Hungary

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, , Hungary

Karolina Korhaz-Rendelointezet

Mosonmagyaróvár, , Hungary

Tolna Megyei Balassa Janos Korhaz

Szekszárd, , Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, , Hungary

Wolfson Medical Center

Holon, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Istituto Clinico Humanitas

Rozzano, Milano, Italy

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

San Donato Milanese, Milano, Italy

Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)

Milan, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Azienda Ospedaliera San Camillo Forlanini

Roma, , Italy

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Nagoya, Aichi-ken, Japan

Sakura-shi, Chiba, Japan

Matsuyama, Ehime, Japan

Chikushino-shi, Fukuoka, Japan

Hiroshima, Hiroshima, Japan

Sapporo, Hokkaido, Japan

Nishinomiya-shi, Hyōgo, Japan

Takamatsu, Kagawa-ken, Japan

Kamakura-shi, Kanagawa, Japan

Okayama, Okayama-ken, Japan

Osaka, Osaka, Japan

Saga, Saga-ken, Japan

Ōtsu, Shiga, Japan

Hamamatsu, Shizuoka, Japan

Bunkyō City, Tokyo-To, Japan

Minatoku, Tokyo-To, Japan

Mitaka-shi, Tokyo-To, Japan

Shinjuku-ku, Tokyo-To, Japan

Wakayama, Wakayama, Japan

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

Klaipeda Republican Hospital, Public Institution

Klaipėda, , Lithuania

Vilnius University Hospital Santariskiu Clinic, Public Institution

Vilnius, , Lithuania

Morales Vargas Centro de Investigacion, S.C.

León, Guanajuato, Mexico

iBiomed Guadalajara

Zapopan, Jalisco, Mexico

Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, Nuevo León, Mexico

Christus Muguerza Sur S.A. de C.V.

Monterrey, Nuevo León, 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

Maastricht University Medical Center

Maastricht, , Netherlands

SP ZOZ Wojewodzki Szpital Zespolony im. J. Sniadeckiego

Bialystok, , Poland

NZOZ Vitamed

Bydgoszcz, , Poland

SP CSK im. prof. K. Gibinskiego SUM

Katowice, , 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 Matki, Dziecka i Mlodziezy

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

TSBIH "Territorial Clinical Hospital"

Krasnoyarsk, , Russia

FSBIH "Central Clinical Hospital of Russian Academy of Sciences"

Moscow, , Russia

SBEIHPE Novosibirsk State Medical University

Novosibirsk, , Russia

FSBI "Scientific Research Institute of Physyology and Basic Medicine" under the SB of RAMS

Novosibirsk, , Russia

BHI of Omsk region Clinical Oncology Dispensary

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

SBIH of Yaroslavl region " Regional Clinical Hospital "

Yaroslavl, , Russia

Clinical Center Zvezdara

Belgrade, , Serbia

Clinical Center Bezanijska kosa

Belgrade, , Serbia

Clinical Center Zemun

Belgrade, , Serbia

Clinical Center Kragujevac

Kragujevac, , Serbia

Clinical Center of Vojvodina

Novi Sad, , Serbia

Univerzitna nemocnica Bratislava, Nemocnica Ruzinov

Bratislava, , Slovakia

KM Management spol. s r.o.

Nitra, , Slovakia

Gastro I, s.r.o.

Prešov, , Slovakia

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

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Complejo Hospitalario de Pontevedra

Pontevedra, , Spain

Karolinska Universitetssjukhuset - Solna

Stockholm, , Sweden

Danderyds Sjukhus AB

Stockholm, , Sweden

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Acibadem Fulya Hospital

Istanbul, , Turkey (Türkiye)

Marmara University Pendik Research and Training Hospital

Istanbul, , Turkey (Türkiye)

RCI Chernivtsi RCH Dep of Surgery Bukovinian SMU

Chernivtsi, , Ukraine

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

Dnipro, , Ukraine

Regional CH Dep of Gastroenterology SHEI Ivano-Frankivsk NMU

Ivano-Frankivsk, , Ukraine

CHI Prof.O.O.Shalimov Kharkiv City Clinical Hospital #2

Kharkiv, , Ukraine

GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine

Kharkiv, , Ukraine

CI A.and O. Tropiny City Clinical Hospital

Kherson, , Ukraine

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

Kyiv, , Ukraine

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

Kyiv, , Ukraine

CI Odesa Regional Clinical Hospital

Odesa, , Ukraine

SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU

Uzhhorod, , Ukraine

Private Small Enterprise Medical Center Pulse

Vinnytsia, , Ukraine

MCIC MC LLC Health Clinic

Vinnytsia, , Ukraine

SI Branch CH of Zaporizhzhia Station-2 of SE Prydniprovska Railway Dept of Surgery Zaporizhzhia SMU

Zaporizhzhia, , Ukraine

Royal Devon and Exeter Hospital (Wonford)

Exeter, Devon, United Kingdom

Whipps Cross University Hospital

London, Greater London, United Kingdom

Royal Free Hospital

London, Greater London, United Kingdom

Countries

United States; Argentina; Australia; Belgium; Bosnia and Herzegovina; Brazil; Bulgaria; Canada; Croatia; Czechia; Denmark; Estonia; Germany; Hungary; Israel; Italy; Japan; Lithuania; Mexico; Netherlands; Poland; Romania; Russia; Serbia; Slovakia; South Korea; Spain; Sweden; 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)

Kobayashi T, Ito H, Ashida T, Yokoyama T, Nagahori M, Inaba T, Shikamura M, Yamaguchi T, Hori T, Pinton P, Watanabe M, Hibi T. Efficacy and safety of a new vedolizumab subcutaneous formulation in Japanese patients with moderately to severely active ulcerative colitis. Intest Res. 2021 Oct;19(4):448-460. doi: 10.5217/ir.2020.00026. Epub 2020 Aug 18.

Reference Type: DERIVED

PMID: 32806876 (View on PubMed)

Sandborn WJ, Baert F, Danese S, Krznaric Z, Kobayashi T, Yao X, Chen J, Rosario M, Bhatia S, Kisfalvi K, D'Haens G, Vermeire S. Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis. Gastroenterology. 2020 Feb;158(3):562-572.e12. doi: 10.1053/j.gastro.2019.08.027. Epub 2019 Aug 28.

Reference Type: DERIVED

PMID: 31470005 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-000480-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1168-0813

Identifier Type: REGISTRY

Identifier Source: secondary_id

16/LO/0089

Identifier Type: REGISTRY

Identifier Source: secondary_id

NL55501.056.15

Identifier Type: REGISTRY

Identifier Source: secondary_id

JapicCTI-163222

Identifier Type: REGISTRY

Identifier Source: secondary_id

189732

Identifier Type: REGISTRY

Identifier Source: secondary_id

163300410A0046

Identifier Type: REGISTRY

Identifier Source: secondary_id

MLN0002SC-3027

Identifier Type: -

Identifier Source: org_study_id