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

Crohn's Disease Clinical Trial

Official title:

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Crohn's Disease Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02611817
• Other study ID #: MLN0002SC-3031
• Secondary ID: U1111-1168-08452
• Status: Completed
• Phase: Phase 3
• Start date: January 4, 2016
• Est. completion date: August 6, 2019

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) as maintenance treatment in participants with moderately to severely active CD who achieved clinical response following administration of vedolizumab intravenous (vedolizumab IV) induction therapy.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 644
• Est. completion date: August 6, 2019
• Est. primary completion date: May 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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-a) 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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Vedolizumab SC 108 mg
Vedolizumab SC Injection.
• Placebo
Vedolizumab placebo-matching SC injection.
• Vedolizumab IV 300 mg
Vedolizumab IV Injection.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Ballarat Base Hospital	Ballarat	Victoria
Australia	Tennyson Centre Day Hospital	Bedford Park	South Australia
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Nepean Hospital	Kingswood	New South Wales
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
Belgium	Imeldaziekenhuis	Bonheiden
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Groeninge - Kennedylaan	Kortrijk
Belgium	ZNA Jan Palfijn	Merksem
Belgium	AZ Delta	Roeselare
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	University Clinical Hospital Mostar	Mostar
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	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	HUCFF-UFRJ - Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro	Rio de Janeiro	Rio Do Janeiro
Brazil	HUGG - Hospital Universitario Gaffree e Guinle	Rio de Janeiro	Rio Do Janeiro
Brazil	Faculdade de Medicina do ABC	Santo Andre	Sao Paulo
Brazil	Irmandade da Santa Casa da Misericordia de Santos	Santos	Sao Paulo
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto	Sao Jose do Rio Preto	Sao Paulo
Bulgaria	MHAT "Hadzhi Dimitar", OOD	Sliven
Bulgaria	"City Clinic UMHAC" EOOD	Sofia
Bulgaria	Fourth MHAT - Sofia EAD	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", EAD	Sofia
Bulgaria	UMHAT 'Tsaritsa Yoanna - ISUL', EAD	Sofia
Canada	Zeidler Ledcor Centre - University of Alberta	Edmonton	Alberta
Canada	LHSC - University Hospital	London	Ontario
Canada	LHSC - Victoria Hospital	London	Ontario
Canada	Toronto Digestive Disease Associates, Inc.	Vaughan	Ontario
Canada	PerCuro Clinical Research Ltd.	Victoria	British Columbia
Czechia	CCBR - Czech Brno, s.r.o..	Brno
Czechia	Hepato-Gastroenterologie HK s.r.o.	Hradec Kralove
Czechia	A-SHINE s.r.o.	Plzen
Czechia	CCBR Czech Prague, s.r.o.	Praha 3
Czechia	Axon Clinical s.r.o.	Praha 5
Denmark	Odense Universitetshospital	Odense C
Denmark	Regionshospitalet Silkeborg	Silkeborg
Estonia	North Estonia Medical Centre Foundation	Tallinn
Germany	DRK Kliniken Berlin Westend	Berlin
Germany	Krankenhaus Waldfriede e. V.	Berlin
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	EUGASTRO GmbH	Leipzig	Sachsen
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz	Rheinland Pfalz
Hungary	Obudai Egeszsegugyi Centrum Kft.	Budapest
Hungary	Pannonia Maganorvosi Centrum	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak	Budapest
Hungary	Pest Megyei Flor Ferenc Korhaz	Kistarcsa
Hungary	Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz	Miskolc
Hungary	Karolina Korhaz-Rendelointezet	Mosonmagyarovar
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszard
Israel	HaEmek Medical Center	Afula
Israel	Soroka University Medical Center	Beer Sheva
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rechovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna
Italy	Azienda Ospedaliera Ospedale Cannizzaro	Catania
Italy	Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)	Milano
Italy	A.O.U. Policlinico di Modena	Modena
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Azienda Ospedaliera Vincenzo Cervello	Palermo
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	I.R.C.C.S Policlinico San Donato	San Donato Milanese (MI)	Milano
Italy	IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Japan	Fukuoka University Chikushi Hospital	Chikushino-shi	Fukuoka-Ken
Japan	Hamamatsu South Hospital	Hamamatsu-shi	Shizuoka-Ken
Japan	Gokeikai Ofuna Chuo Hospital	Kamakura-shi	Kanagawa-Ken
Japan	Kitasato University Kitasato Institute Hospital	Minato-ku	Tokyo-To
Japan	Iwate Medical University Hospital	Morioka-shi	Iwate-Ken
Japan	Hyogo College of Medicine Hospital	Nishinomiya-shi	Hyogo-Ken
Japan	Kinshukai Infusion Clinic	Osaka-shi	Osaka-Fu
Japan	Saga University Hospital	Saga-shi	Saga-Ken
Japan	Toho University Sakura Medical Center	Sakura-shi	Chiba-Ken
Japan	Sapporo-Kosei General Hospital	Sapporo-shi	Hokkaido
Japan	Tokushukai Sapporo Higashi Tokushukai Hospital	Sapporo-shi	Hokkaido
Japan	Tokushukai Sapporo Tokushukai Hospital	Sapporo-shi	Hokkaido
Japan	JCHO Tokyo Yamate Medical Center	Shinjuku-ku	Tokyo-To
Japan	Wakayama Medical University Hospital	Wakayama-shi	Wakayama-Ken
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam University Hospital	Daegu
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Vilnius University Hospital Santariskiu Clinic, Public Institution	Vilnius
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango
Mexico	Centro de Investigacion Farmacologica del Bajio, S.C.	Leon	Guanajuato
Mexico	Morales Vargas Centro de Investigacion, S.C.	Leon	Guanajuato
Mexico	Sociedad de Metabolismo y Corazon S.C	Veracruz
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Albert Schweitzer Ziekenhuis, Dordwijk	Dordrecht
Netherlands	Erasmus Medisch Centrum	Rotterdam
Poland	NZOZ Vitamed	Bydgoszcz
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 MDM	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	Kazan State Medical University	Kazan
Russian Federation	TSBIH "Territorial Clinical Hospital"	Krasnoyarsk
Russian Federation	FSBSI "Scientific and Research Institute of Physiology and Basic Medicine"	Novosibirsk
Russian Federation	SBEIHPE Novosibirsk State Medical University	Novosibirsk
Russian Federation	BHI of Omsk region Clinical Oncology Dispensary	Omsk
Russian Federation	SBEI of HPE "Omsk SMA" SBEI HPE "Omsk State Medical University" of the MoH of the RF	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 # 40 of Kurortnyi region"	Sestroretsk
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 Helth Centre Zvezdara	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center of Vojvodina	Novi Sad
Slovakia	Fakultna nemocnica s poliklinikou F.D. Roosevelta	Banska Bystrica
Slovakia	Univerzitna nemocnica Bratislava, Nemocnica Ruzinov	Bratislava
South Africa	Dr JP Wright Practice	Cape Town	Western Cape
South Africa	Dr CCM Ziady Practice	Pretoria	Gauteng
Sweden	Karolinska Universitetssjukhuset - Solna	Stockholm
Taiwan	Mackay Memorial Hospital	Taipei
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Haydarpasa Numune Training and Research Hospital	Istanbul
Turkey	Marmara University Pendik Research and Training Hospital	Istanbul
Turkey	Kocaeli Derince Training and Research Hospital	Kocaeli
Turkey	Mersin University Medical Faculty	Mersin
Ukraine	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	CI of Kyiv RC Kyiv Regional Clinical Hospital	Kyiv
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	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	MCIC MC LLC Health Clinic	Vinnytsia
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	CI City Hospital #1	Zaporizhzhia
United Kingdom	University Hospital Coventry	Coventry	West Midlands
United Kingdom	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 States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Gastroenterology Associates, LLC	Baton Rouge	Louisiana
United States	Ehrhardt Clinical Research, LLC	Belton	Missouri
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
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	Rush University Medical Center	Chicago	Illinois
United States	Tri-State Gastroenterology Associates	Crestview Hills	Kentucky
United States	Gastroenterology Center of the MidSouth PC	Germantown	Tennessee
United States	Long Island Clinical Research Associates	Great Neck	New York
United States	Medical Research Center of Connecticut, LLC	Hamden	Connecticut
United States	Grand Teton Research Group, PLL	Idaho Falls	Idaho
United States	Nature Coast Clinical Research, LLC	Inverness	Florida
United States	Gastro-Enterology Research of Lima	Lima	Ohio
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	Allegiance Research Specialists, LLC	Milwaukee	Wisconsin
United States	Gastroenterology Group of Naples	Naples	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Arizona Arthritis & Rheumatology Research, PLLC	Phoenix	Arizona
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	San Antonio Gastroenterology	San Antonio	Texas
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
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	Carle Foundation Hospital	Urbana	Illinois
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,  Australia,  Belgium,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Czechia,  Denmark,  Estonia,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Lithuania,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Sweden,  Taiwan,  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 Crohn's Disease Activity Index (CDAI) score less than or equal to (<=) 150 at Week 52. A CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days includes participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI score is equal to (=) sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.	Week 52
Secondary	Percentage of Participants Achieving Enhanced Clinical Response at Week 52	Enhanced clinical response is defined as a decrease from Baseline of greater than or equal to (>=) 100 points in the CDAI score at Week 52. A CDAI is a multi-item instrument which measures severity of active CD monitored over 7 days includes participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.	Week 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 CDAI score <=150 at Week 52. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.	Week 52
Secondary	Percentage of TNF-alpha Antagonist Naive Participants Achieving Clinical Remission at Week 52	Clinical remission is defined as CDAI score <=150 at Week 52. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.	Week 52