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

Colitis, Ulcerative Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02611830
• Other study ID #: MLN0002SC-3027
• Secondary ID: 2015-000480-14U1
• Status: Completed
• Phase: Phase 3
• Start date: December 18, 2015
• Est. completion date: August 21, 2018

Study information

• Verified date: May 2022
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 383
• Est. completion date: August 21, 2018
• Est. primary completion date: May 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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-a) 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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Vedolizumab 300 mg IV
Vedolizumab intravenous infusion
• Placebo IV
Vedolizumab intravenous infusion placebo
• Vedolizumab 108 mg SC
Vedolizumab subcutaneous injection
• Placebo SC
Vedolizumab subcutaneous injection placebo

Locations

Country	Name	City	State
Argentina	Expertia S.A- Mautalen Salud e Investigacion	Ciudad Autonoma Buenos Aires
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Clinique Saint-Pierre	Ottignies
Belgium	AZ Delta	Roeselare
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska	Banja Luka
Brazil	UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu	Botucatu	Sao Paulo
Brazil	Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda	Goiania	Goias
Brazil	HUCFF-UFRJ - Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro	Rio de Janeiro	Rio Do Janeiro
Brazil	Faculdade de Medicina do ABC	Santo Andre	Sao Paulo
Bulgaria	MHAT 'Avis Medica' OOD	Pleven
Bulgaria	MHAT - Silistra AD	Silistra
Bulgaria	MHAT "Hadzhi Dimitar", OOD	Sliven
Bulgaria	"City Clinic UMHAC" EOOD	Sofia
Bulgaria	Second MHAT - Sofia AD	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", EAD	Sofia
Bulgaria	UMHAT 'Tsaritsa Yoanna - ISUL', EAD	Sofia
Bulgaria	Medical Center "Nov Rehabilitatsionen Tsentar", EOOD	Stara Zagora
Canada	LHSC - Victoria Hospital	London	Ontario
Canada	London Health Science Centre	London	Ontario
Canada	Toronto Digestive Disease Associates, Inc.	Vaughan	Ontario
Croatia	Clinical Hospital Centre Osijek	Osijek
Croatia	Clinical Hospital Centre Rijeka	Rijeka
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Croatia	Clinical Hospital Dubrava	Zagreb
Czechia	Ccbr-Synarc A/S	Brno
Czechia	Hepato-Gastroenterologie HK, s.r.o.	Hradec Kralove
Czechia	A-SHINE s.r.o.	Plzen
Czechia	Ccbr-Synarc A/S	Praha 3
Czechia	Axon Clinical, s.r.o.	Praha 8
Denmark	Odense Universitetshospital	Odense C
Estonia	West Tallinn Central Hospital	Tallinn
Germany	Krankenhaus Waldfriede e. V.	Berlin
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	EUGASTRO GmbH	Leipzig	Sachsen
Hungary	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	Mosonmagyarovar
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszard
Israel	Wolfson Medical Center	Holon
Israel	Chaim Sheba Medical Center	Ramat Gan
Italy	Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)	Milano
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Italy	I.R.C.C.S Policlinico San Donato	San Donato Milanese	Milano
Italy	IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam University Hospital	Daegu
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Klaipeda Republican Hospital, Public Institution	Klaipeda
Lithuania	Vilnius University Hospital Santariskiu Clinic, Public Institution	Vilnius
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango
Mexico	Morales Vargas Centro de Investigacion, S.C.	Leon	Guanajuato
Mexico	Christus Muguerza Sur S.A. de C.V.	Monterrey	Nuevo Leon
Mexico	Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo Leon
Mexico	Sociedad de Metabolismo y Corazon S.C	Veracruz
Mexico	iBiomed Guadalajara	Zapopan	Jalisco
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Albert Schweitzer Ziekenhuis, Dordwijk	Dordrecht
Netherlands	Maastricht University Medical Center	Maastricht
Poland	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	Santa Familia Centrum Badan, Profilaktyki i Leczenia	Lodz
Poland	SPZOZ Uniwersytecki Szpital Klin. nr 1 im.N.Barlickiego UM	Lodz
Poland	GASTROMED Sp. z o.o.	Lublin
Poland	Twoja Przychodnia-Szczecinskie Centrum Medyczne	Szczecin
Poland	Centralny Szpital Kliniczny MSW w Warszawie	Warszawa
Poland	Centrum Onkologii-Instytut im. M. Sklodowskiej Curie	Warszawa
Poland	Centrum Zdrowia Matki, Dziecka i Mlodziezy	Warszawa
Poland	Nzoz Vivamed	Warszawa
Poland	Ars-Medica S.C Rybak Maria, Rybak Zbigniew	Wroclaw
Poland	LexMedica Osrodek Badan Klinicznych	Wroclaw
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	Spitalul Clinic Colentina	Bucuresti
Romania	S.C Centrul de Gastroenterologie Dr. Goldis S.R.L	Timisoara
Russian Federation	TSBIH "Territorial Clinical Hospital"	Krasnoyarsk
Russian Federation	FSBIH "Central Clinical Hospital of Russian Academy of Sciences"	Moscow
Russian Federation	FSBI "Scientific Research Institute of Physyology and Basic Medicine" under the SB of RAMS	Novosibirsk
Russian Federation	SBEIHPE Novosibirsk State Medical University	Novosibirsk
Russian Federation	BHI of Omsk region Clinical Oncology Dispensary	Omsk
Russian Federation	SBEI HPE "Rostov State Medical University" of the MoH of the RF	Rostov-on-Don
Russian Federation	LLC "RIAT SPb"	Saint-Petersburg
Russian Federation	SPb SBIH "City Hospital of Saint Martyr Elizaveta"	St. Petersburg
Russian Federation	SBIH of Yaroslavl region " Regional Clinical Hospital "	Yaroslavl
Serbia	Clinical Center Bezanijska kosa	Belgrade
Serbia	Clinical Center Zemun	Belgrade
Serbia	Clinical Center Zvezdara	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center of Vojvodina	Novi Sad
Slovakia	Univerzitna nemocnica Bratislava, Nemocnica Ruzinov	Bratislava
Slovakia	KM Management spol. s r.o.	Nitra
Slovakia	Gastro I, s.r.o.	Presov
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Complejo Hospitalario de Pontevedra	Pontevedra
Sweden	Danderyds Sjukhus AB	Stockholm
Sweden	Karolinska Universitetssjukhuset - Solna	Stockholm
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Acibadem Fulya Hospital	Istanbul
Turkey	Marmara University Pendik Research and Training Hospital	Istanbul
Ukraine	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	Uzhgorod
Ukraine	MCIC MC LLC Health Clinic	Vinnytsia
Ukraine	Private Small Enterprise Medical Center Pulse	Vinnytsia
Ukraine	SI Branch CH of Zaporizhzhia Station-2 of SE Prydniprovska Railway Dept of Surgery Zaporizhzhia SMU	Zaporizhzhia
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter	Devon
United Kingdom	Royal Free Hospital	London	Greater London
United Kingdom	Whipps Cross University Hospital	London	Greater London
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Gastroenterology Associates, LLC	Baton Rouge	Louisiana
United States	Ehrhardt Clinical Research, LLC	Belton	Missouri
United States	Gastroenterology Associates of Tidewater	Chesapeake	Virginia
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	Metropolitan Gastroenterology Group, PC, Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	Tri-State Gastroenterology Associates	Crestview Hills	Kentucky
United States	Dayton Gastroenterology, Inc	Dayton	Ohio
United States	Gastro One	Germantown	Tennessee
United States	Long Island Clinical Research Associates	Great Neck	New York
United States	Nature Coast Clinical Research, LLC	Inverness	Florida
United States	Florida Center for Gastroenterology	Largo	Florida
United States	Arkansas Primary Care Clinic, PA	Little Rock	Arkansas
United States	Gastroenterology Associates of Central Georgia	Macon	Georgia
United States	L & L Research Choices, Inc.	Miami	Florida
United States	Middlesex Gastroenterology Associates	Middletown	Connecticut
United States	Gastroenterology Group of Naples	Naples	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Research Concierge, LLC	Owensboro	Kentucky
United States	Premier Medical Group of the Hudson Valley, PC	Poughkeepsie	New York
United States	Virginia Mason Seattle Main Clinic	Seattle	Washington
United States	Atlanta Gastroenterology Specialists, PC	Suwanee	Georgia
United States	Cotton-O'Neil Clinical Research Center, Digestive Health	Topeka	Kansas
United States	Options Health Research	Tulsa	Oklahoma
United States	Tyler Research Institute, LLC	Tyler	Texas
United States	Rocky Mountain Clinical Research, LLC	Wheat Ridge	Colorado
United States	Shafran Gastroenterology Center	Winter Park	Florida
United States	Gastroenterology Associates of Western Michigan, P.L.C.	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Croatia,  Czechia,  Denmark,  Estonia,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Lithuania,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Clinical Remission at Week 52	Clinical remission is defined as a complete Mayo score = 2 points and no individual subscore > 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).	Week 52
Secondary	Percentage of Participants Achieving Mucosal Healing at Week 52	Mucosal healing is defined as Mayo endoscopic subscore =1 point. The findings on endoscopy scale ranges from 0 to 3, where 0=normal or inactive disease 1=mild disease (erythema, decreased vascular pattern, mild friability) 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 3=severe disease (spontaneous bleeding, ulceration).	Week 52
Secondary	Percentage of Participants Achieving Durable Clinical Response at Week 6 and Week 52	Durable clinical response is defined as clinical response at both Weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of =3 points and =30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of =1 point or absolute rectal bleeding subscore of =1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).	Baseline, Weeks 6 and 52
Secondary	Percentage of Participants Achieving Durable Clinical Remission at Week 6 and Week 52	Durable clinical remission is defined as clinical remission at both Weeks 6 and 52. Clinical remission is defined as a complete Mayo score of less than or equal to (=) 2 points and no individual subscore greater than (>) 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).	Weeks 6 and 52
Secondary	Percentage of Participants Achieving Corticosteroid-free Remission at Week 52	Corticosteroid-free remission is defined as participants using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. Clinical remission is defined as a complete Mayo score of = 2 points and no individual subscore > 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).	Week 52