Clinical trial NCT02611830: Efficacy and Safety of Vedolizumab Subcutaneously (SC) as Maintenance Therapy in Ulcerative Colitis
Official title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study, With a Vedolizumab IV Reference Arm, to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colitis, Ulcerative
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-11-23
Enrollment: 383
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants Achieving Clinical Remission at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Percentage of Participants Achieving Mucosal Healing at Week 52
timeFrame: Week 52
measure: Percentage of Participants Achieving Durable Clinical Response at Week 6 and Week 52
timeFrame: Baseline, Weeks 6 and 52
measure: Percentage of Participants Achieving Durable Clinical Remission at Week 6 and Week 52
timeFrame: Weeks 6 and 52
measure: Percentage of Participants Achieving Corticosteroid-free Remission at Week 52
timeFrame: Week 52
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic, PA
state: Arkansas
city: Wheat Ridge
country: United States
facility: Rocky Mountain Clinical Research, LLC
state: Colorado
city: Middletown
country: United States
facility: Middlesex Gastroenterology Associates
state: Connecticut
city: Inverness
country: United States
facility: Nature Coast Clinical Research, LLC
state: Florida
city: Largo
country: United States
facility: Florida Center for Gastroenterology
state: Florida
city: Miami
country: United States
facility: L & L Research Choices, Inc.
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group of Naples
state: Florida
city: Winter Park
country: United States
facility: Shafran Gastroenterology Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Macon
country: United States
facility: Gastroenterology Associates of Central Georgia
state: Georgia
city: Suwanee
country: United States
facility: Atlanta Gastroenterology Specialists, PC
state: Georgia
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center, Digestive Health
state: Kansas
city: Crestview Hills
country: United States
facility: Tri-State Gastroenterology Associates
state: Kentucky
city: Owensboro
country: United States
facility: Research Concierge, LLC
state: Kentucky
city: Baton Rouge
country: United States
facility: Gastroenterology Associates, LLC
state: Louisiana
city: Chevy Chase
country: United States
facility: Metropolitan Gastroenterology Group, PC, Chevy Chase Clinical Research
state: Maryland
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, P.L.C.
state: Michigan
city: Belton
country: United States
facility: Ehrhardt Clinical Research, LLC
state: Missouri
city: Great Neck
country: United States
facility: Long Island Clinical Research Associates
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley, PC
state: New York
city: Dayton
country: United States
facility: Dayton Gastroenterology, Inc
state: Ohio
city: Tulsa
country: United States
facility: Options Health Research
state: Oklahoma
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Tyler
country: United States
facility: Tyler Research Institute, LLC
state: Texas
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Seattle Main Clinic
state: Washington
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Expertia S.A- Mautalen Salud e Investigacion
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Roeselare
country: Belgium
facility: AZ Delta
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska
city: Goiania
country: Brazil
facility: Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda
state: Goias
city: Rio de Janeiro
country: Brazil
facility: HUCFF-UFRJ - Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro
state: Rio Do Janeiro
city: Botucatu
country: Brazil
facility: UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC
state: Sao Paulo
city: Pleven
country: Bulgaria
facility: MHAT 'Avis Medica' OOD
city: Silistra
country: Bulgaria
facility: MHAT - Silistra AD
city: Sliven
country: Bulgaria
facility: MHAT "Hadzhi Dimitar", OOD
city: Sofia
country: Bulgaria
facility: Second MHAT - Sofia AD
city: Sofia
country: Bulgaria
facility: "City Clinic UMHAC" EOOD
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski", EAD
city: Sofia
country: Bulgaria
facility: UMHAT 'Tsaritsa Yoanna - ISUL', EAD
city: Stara Zagora
country: Bulgaria
facility: Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
city: London
country: Canada
facility: London Health Science Centre
state: Ontario
city: London
country: Canada
facility: LHSC - Victoria Hospital
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates, Inc.
state: Ontario
city: Osijek
country: Croatia
facility: Clinical Hospital Centre Osijek
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre Rijeka
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava
city: Brno
country: Czechia
facility: Ccbr-Synarc A/S
city: Hradec Kralove
country: Czechia
facility: Hepato-Gastroenterologie HK, s.r.o.
city: Plzen
country: Czechia
facility: A-SHINE s.r.o.
city: Praha 3
country: Czechia
facility: Ccbr-Synarc A/S
city: Praha 8
country: Czechia
facility: Axon Clinical, s.r.o.
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Leipzig
country: Germany
facility: EUGASTRO GmbH
state: Sachsen
city: Berlin
country: Germany
facility: Krankenhaus Waldfriede e. V.
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft.
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Mosonmagyarovar
country: Hungary
facility: Karolina Korhaz-Rendelointezet
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Szekszard
country: Hungary
facility: Tolna Megyei Balassa Janos Korhaz
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
state: Foggia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: San Donato Milanese
country: Italy
facility: I.R.C.C.S Policlinico San Donato
state: Milano
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Nagoya-shi
country: Japan
state: Aichi-Ken
city: Sakura-shi
country: Japan
state: Chiba-Ken
city: Matsuyama-shi
country: Japan
state: Ehime-Ken
city: Chikushino-shi
country: Japan
state: Fukuoka-Ken
city: Hiroshima-shi
country: Japan
state: Hiroshima-Ken
city: Sapporo-shi
country: Japan
state: Hokkaido
city: Nishinomiya-shi
country: Japan
state: Hyogo-Ken
city: Takamatsu-shi
country: Japan
state: Kagawa-Ken
city: Kamakura-shi
country: Japan
state: Kanagawa-Ken
city: Okayama-shi
country: Japan
state: Okayama-Ken
city: Osaka-shi
country: Japan
state: Osaka-Fu
city: Saga-shi
country: Japan
state: Saga-Ken
city: Otsu-shi
country: Japan
state: Shiga-Ken
city: Hamamatsu-shi
country: Japan
state: Shizuoka-Ken
city: Bunkyo-ku
country: Japan
state: Tokyo-To
city: Minato-ku
country: Japan
state: Tokyo-To
city: Mitaka-shi
country: Japan
state: Tokyo-To
city: Shinjuku-ku
country: Japan
state: Tokyo-To
city: Wakayama-shi
country: Japan
state: Wakayama-Ken
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Klaipeda
country: Lithuania
facility: Klaipeda Republican Hospital, Public Institution
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinic, Public Institution
city: Leon
country: Mexico
facility: Morales Vargas Centro de Investigacion, S.C.
state: Guanajuato
city: Zapopan
country: Mexico
facility: iBiomed Guadalajara
state: Jalisco
city: Monterrey
country: Mexico
facility: Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Christus Muguerza Sur S.A. de C.V.
state: Nuevo Leon
city: Durango
country: Mexico
facility: Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
city: Veracruz
country: Mexico
facility: Sociedad de Metabolismo y Corazon S.C
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, Dordwijk
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Bialystok
country: Poland
facility: SP ZOZ Wojewodzki Szpital Zespolony im. J. Sniadeckiego
city: Bydgoszcz
country: Poland
facility: NZOZ Vitamed
city: Katowice
country: Poland
facility: SP CSK im. prof. K. Gibinskiego SUM
city: Krakow
country: Poland
facility: Gabinet Endoskopii Przewodu Pokarmowego
city: Lodz
country: Poland
facility: SPZOZ Uniwersytecki Szpital Klin. nr 1 im.N.Barlickiego UM
city: Lodz
country: Poland
facility: Santa Familia Centrum Badan, Profilaktyki i Leczenia
city: Lublin
country: Poland
facility: GASTROMED Sp. z o.o.
city: Szczecin
country: Poland
facility: Twoja Przychodnia-Szczecinskie Centrum Medyczne
city: Warszawa
country: Poland
facility: Centrum Zdrowia Matki, Dziecka i Mlodziezy
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSW w Warszawie
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
city: Warszawa
country: Poland
facility: Nzoz Vivamed
city: Wroclaw
country: Poland
facility: LexMedica Osrodek Badan Klinicznych
city: Wroclaw
country: Poland
facility: Ars-Medica S.C Rybak Maria, Rybak Zbigniew
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni
city: Timisoara
country: Romania
facility: S.C Centrul de Gastroenterologie Dr. Goldis S.R.L
city: Krasnoyarsk
country: Russian Federation
facility: TSBIH "Territorial Clinical Hospital"
city: Moscow
country: Russian Federation
facility: FSBIH "Central Clinical Hospital of Russian Academy of Sciences"
city: Novosibirsk
country: Russian Federation
facility: SBEIHPE Novosibirsk State Medical University
city: Novosibirsk
country: Russian Federation
facility: FSBI "Scientific Research Institute of Physyology and Basic Medicine" under the SB of RAMS
city: Omsk
country: Russian Federation
facility: BHI of Omsk region Clinical Oncology Dispensary
city: Rostov-on-Don
country: Russian Federation
facility: SBEI HPE "Rostov State Medical University" of the MoH of the RF
city: Saint-Petersburg
country: Russian Federation
facility: LLC "RIAT SPb"
city: St. Petersburg
country: Russian Federation
facility: SPb SBIH "City Hospital of Saint Martyr Elizaveta"
city: Yaroslavl
country: Russian Federation
facility: SBIH of Yaroslavl region " Regional Clinical Hospital "
city: Belgrade
country: Serbia
facility: Clinical Center Zvezdara
city: Belgrade
country: Serbia
facility: Clinical Center Bezanijska kosa
city: Belgrade
country: Serbia
facility: Clinical Center Zemun
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava, Nemocnica Ruzinov
city: Nitra
country: Slovakia
facility: KM Management spol. s r.o.
city: Presov
country: Slovakia
facility: Gastro I, s.r.o.
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset - Solna
city: Stockholm
country: Sweden
facility: Danderyds Sjukhus AB
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Istanbul
country: Turkey
facility: Acibadem Fulya Hospital
city: Istanbul
country: Turkey
facility: Marmara University Pendik Research and Training Hospital
city: Chernivtsi
country: Ukraine
facility: RCI Chernivtsi RCH Dep of Surgery Bukovinian SMU
city: Dnipro
country: Ukraine
facility: SI Institute of Gastroenterology of NAMSU Dept of Stomach & Duodenum Diseases, D&ThN SI DMA of MoHU
city: Ivano-Frankivsk
country: Ukraine
facility: Regional CH Dep of Gastroenterology SHEI Ivano-Frankivsk NMU
city: Kharkiv
country: Ukraine
facility: CHI Prof.O.O.Shalimov Kharkiv City Clinical Hospital #2
city: Kharkiv
country: Ukraine
facility: GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
city: Kherson
country: Ukraine
facility: CI A.and O. Tropiny City Clinical Hospital
city: Kyiv
country: Ukraine
facility: Kyiv CCH #12 Dept of Therapy O.O.Bogomolets NMU
city: Kyiv
country: Ukraine
facility: MI of Healthcare Kyiv RCH P.L. Shupyk NMA of PGE
city: Odesa
country: Ukraine
facility: CI Odesa Regional Clinical Hospital
city: Uzhgorod
country: Ukraine
facility: SI Divisional Clinical Hospital of Uzhgorod Station of ST&BA LZ Dep of Therapy SHEI Uzhgorod NU
city: Vinnytsia
country: Ukraine
facility: Private Small Enterprise Medical Center Pulse
city: Vinnytsia
country: Ukraine
facility: MCIC MC LLC Health Clinic
city: Zaporizhzhia
country: Ukraine
facility: SI Branch CH of Zaporizhzhia Station-2 of SE Prydniprovska Railway Dept of Surgery Zaporizhzhia SMU
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital (Wonford)
state: Devon
city: London
country: United Kingdom
facility: Whipps Cross University Hospital
state: Greater London
city: London
country: United Kingdom
facility: Royal Free Hospital
state: Greater London
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.