A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors

NCT02171429 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GA289492013-004277-27
• Study Type: interventional
• Target: 358
• Locations: 19 countries
• Sites: 90

Brief Summary

This Phase III, double-blind, placebo and active-comparator controlled, multicenter study will investigate the efficacy and safety of etrolizumab in induction of remission in participants with moderately to severely active ulcerative colitis (UC) who are naIve to tumor necrosis factor (TNF) inhibitors and refractory to or intolerant of prior immunosuppressant and/or corticosteroid treatment. In addition to this study, a second Phase III trial with identical study design (GA28948; NCT02163759) was independently conducted.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants in Remission at Week 10 With Etrolizumab Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28949 Population

  The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the Cochran-Mantel-Haenszel test adjusted the difference in remission rates and associated 95% confidence interval for the stratification factors.

  Week 10

Secondary Outcomes (26)

• Percentage of Participants in Remission at Week 10 With Etrolizumab Compared With Adalimumab, as Determined by the MCS, GA28949 Population

  Week 10

• Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population

  Week 10

• Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28949 Population

  Week 10

• Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population

  Week 10

• Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the Mayo Endoscopy Subscore, GA28949 Population

  Week 10

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to etrolizumab up to Week 12 and placebo matching to adalimumab up to Week 8.

Other: Adalimumab Placebo; Other: Etrolizumab Placebo

Adalimumab

ACTIVE COMPARATOR

Participants will receive adalimumab up to Week 8 and placebo matching to etrolizumab up to Week 12.

Drug: Adalimumab; Other: Etrolizumab Placebo

Etrolizumab

EXPERIMENTAL

Participants will receive etrolizumab up to Week 12 and placebo matching to adalimumab up to Week 8.

Other: Adalimumab Placebo; Drug: Etrolizumab

Interventions

Adalimumab DRUG

Adalimumab 160 milligrams (mg) will be administered subcutaneously (SC) at Week 0; 80 mg SC at Week 2; 40 mg SC at Weeks 4, 6 and 8.

Also known as: Humira

Adalimumab

Adalimumab Placebo OTHER

Placebo matching to adalimumab will be administered SC at Weeks 0, 2, 4, 6, and 8.

Etrolizumab; Placebo

Etrolizumab DRUG

Etrolizumab 105 mg will be administered SC every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).

Also known as: PRO145223, RO5490261, RG7413

Etrolizumab

Etrolizumab Placebo OTHER

Placebo matching to etrolizumab will be administered SC once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).

Adalimumab; Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of ulcerative colitis (UC) established at least 3 months prior to randomization (Day 1)
• Moderately to severely active UC as determined by the MCS
• Naive to treatment with TNF inhibitor therapy
• An inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment
• Background UC therapy may include oral 5-aminosalisylate (5-ASA), budesonide, oral corticosteroids, probiotics, azathioprine (AZA), 6-mercaptopurine (6MP), or methotrexate (MTX) if doses have been stable for:
• AZA, 6-MP, MTX: 8 weeks immediately prior to randomization
• ASA: 4 weeks immediately prior to randomization
• Corticosteroids: 4 weeks immediately prior to randomization; if corticosteroids are being tapered, dose has to be stable for at least 2 weeks prior to randomization
• Use of highly effective contraception method as defined by the protocol
• Have received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening

You may not qualify if:

• Prior extensive colonic resection, subtotal or total colectomy, or planned surgery for UC
• Past or present ileostomy or colostomy
• Diagnosis of indeterminate colitis
• Suspicion of ischemic colitis, radiation colitis, or microscopic colitis
• Diagnosis of toxic megacolon within 12 months of initial screening visit
• Any diagnosis of Crohn's disease
• Past or present fistula or abdominal abscess
• A history or current evidence of colonic mucosal dysplasia
• Patients with any stricture (stenosis) of the colon
• Patients with history or evidence of adenomatous colonic polyps that have not been removed
• Prior treatment with TNF-alpha antagonists
• Any prior treatment with etrolizumab or other anti-integrin agents
• Any prior treatment with rituximab
• Any treatment with tofacitinib during screening
• Any prior treatment with anti-adhesion molecules

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (90)

Center For Digestive Health

Orlando, Florida, 32803, United States

Location

Internal Medicine Specialists

Orlando, Florida, 32806, United States

Location

Cotton-O'Neil Clinical Research Center, Digestive Health

Topeka, Kansas, 66606, United States

Location

Great Lakes Gastroenterology Research, LLC

Mentor, Ohio, 44060, United States

Location

Centro de Investigaciones Medicas Mar Del Plata

Mar del Plata, B7600DHK, Argentina

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Footscray Hospital; Gastroenterology

Footscray, Victoria, 3011, Australia

Location

Hospital Universitario Walter Cantidio - UFC

Fortaleza, Ceará, 60430-370, Brazil

Location

Hospital Universitario Prof Edgar Santos-Ufba; Ambulatorio Magalhaes Neto 3Andar- Dermatologia

Salvador, Estado de Bahia, 41110-170, Brazil

Location

Centro Digestivo de Curitiba

Curitiba, Paraná, 80430-160, Brazil

Location

Hospital Ernesto Dornelles

Porto Alegre, Rio Grande do Sul, 90160-092, Brazil

Location

Pesquisare Saúde Sociedade Simples

Santo André, São Paulo, 09080-000, Brazil

Location

Medical Centre "Asklepii", OOD

Dupnitsa, 2600, Bulgaria

Location

DCC Sv. Pantaleymon OOD

Pleven, 5800, Bulgaria

Location

Medical center Medconsult Pleven OOD

Pleven, 5800, Bulgaria

Location

MHAT - Ruse, AD

Rousse, 7002, Bulgaria

Location

MHAT "Hadzhi Dimitar", OOD

Sliven, 8800, Bulgaria

Location

"City Clinic UMHAC" EOOD

Sofia, 1407, Bulgaria

Location

Medical center CONVEX EOOD

Sofia, 1680, Bulgaria

Location

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD

Stara Zagora, 6000, Bulgaria

Location

MHAT 'Sv. Marina', EAD

Varna, 9010, Bulgaria

Location

RTS - Fundación Valle de Lili

Cali, 0, Colombia

Location

Instituto de Coloproctologia ICO S.A.S.

Medellín, 050025, Colombia

Location

Clinical Hospital Centre Osijek

Osijek, 31000, Croatia

Location

Clinical Hospital Sveti Duh

Zagreb, 10000, Croatia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Hepato-Gastroenterologie HK, s.r.o.

Hradec Králové, 500 12, Czechia

Location

PreventaMed, s.r.o.

Olomouc, 779 00, Czechia

Location

Pardubicka krajska nemocnice, a.s.

Pardubice, 532 03, Czechia

Location

ISCARE a.s.

Prague, 170 04, Czechia

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

University General Hospital of Heraklion

Heraklion, 711 10, Greece

Location

Petz Aladar Megyei Oktato Korhaz

Győr, 9024, Hungary

Location

Central Outpatient Clinic

Daugavpils, LV-5401, Latvia

Location

Pauls Stradins Clinical University Hospital

Riga, LV-1002, Latvia

Location

Digestive Diseases Center "Gastro"

Riga, LV-1079, Latvia

Location

Hospital of Lithuanian University of Health. Sciences Kaunas Clinics

Kaunas, 50009, Lithuania

Location

Klaipeda Seamen's Hospital, Public Institution

Klaipėda, 92288, Lithuania

Location

Vilnius University Hospital Santariskiu Clinic, Public Institution; Cardiology

Vilnius, LT-08661, Lithuania

Location

Hospital Raja Perempuan Zainab II; Department of Medicine

Kota Bharu, 15586, Malaysia

Location

Pusat Perubatan Universiti Kebangsaan Malaysia

Kuala Lumpur, 56000, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Hospital Tengku Ampuan Afzan

Kuala Pahang, 25100, Malaysia

Location

North Shore Hospital

Auckland, 0620, New Zealand

Location

Dunedin Hospital

Dunedin, New Zealand

Location

Waikato Hospital

Hamilton, 3248, New Zealand

Location

Shakespeare Specialist Group

Takapuna, 0620, New Zealand

Location

Tauranga Hospital

Tauranga, 3143, New Zealand

Location

Pro Familia Altera Sp z o.o.

Katowice, 40-645, Poland

Location

Nzoz All-Medicus

Katowice, 40-660, Poland

Location

Uniwersyteckie Centrum Kliniczne im. prof. K. Gibinskiego SUM

Katowice, 40-752, Poland

Location

Centrum Opieki Zdrowotnej Orkan-Med

Ksawerów, 95-054, Poland

Location

AppleTreeClinics Sp. z o.o.

Lodz, 90-349, Poland

Location

Allmedica Badania Kliniczne Sp z o.o. Sp K.

Nowy Targ, 34-400, Poland

Location

Centrum Medyczne Medyk

Rzeszów, 35-055, Poland

Location

Gabinet Lekarski, Bartosz Korczowski

Rzeszów, 35-302, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej SONOMED

Szczecin, 70-351, Poland

Location

Endoterapia PFG Sp. z o.o.

Warsaw, 02-653, Poland

Location

LexMedica Osrodek Badan Klinicznych

Wroclaw, 53-114, Poland

Location

SBIH City Clinical Hospital #31

Saint Petersburg, Sankt-Peterburg, 197110, Russia

Location

SBEI HPE Altai State Medical University of MoH and SD; Out-patient Department

Barnaul, 656038, Russia

Location

Irkutsk State Medical Academy of Continuing Education

Irkutsk, Russia

Location

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

Novosibirsk, 630117, Russia

Location

BHI of Omsk region Clinical Oncology Dispensary

Omsk, 644013, Russia

Location

Center of Emergency and Radiation Medicine; Pulmonology

Saint Petersburg, 194044, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

SPb SHI "City Hospital #9"

Saint Petersburg, 197110, Russia

Location

FSBEI HE "Stavropol State Medical University" of Ministry of Healthcare of Russian Federation

Stavropol, 355018, Russia

Location

Voronezh Regional Clinical Hospital #1

Voronezh, 394066, Russia

Location

Ankara Diskapi Yildirim Beyazit Training and Research Hospital; Gastroenterology

Ankara, 06110, Turkey (Türkiye)

Location

Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Medical Oncology

Gaziantep, 27310, Turkey (Türkiye)

Location

Haydarpasa Numune Training and Research Hospital; Gastroenterology

Istanbul, 34668, Turkey (Türkiye)

Location

Kocaeli Universitesi Tip Fakultesi

Kocaeli, 41380, Turkey (Türkiye)

Location

CI of SRC Sumy RCH Dept of Gasroenterology Sumy SU MI

Sumy, Kharkiv Governorate, 40022, Ukraine

Location

CNE Kyiv CCH #18

Kyiv, KIEV Governorate, 01030, Ukraine

Location

CI of Kyiv RC Kyiv Regional Clinical Hospital

Kyiv, KIEV Governorate, 04107, Ukraine

Location

Med Center of International Institute of Clinical Trials LLC; Medical Center "OK!Clinic+"

Kyiv, KIEV Governorate, 2091, Ukraine

Location

A.Novak Transcarpathian Regional Clinical Hospital

Uzhhorod, KIEV Governorate, 88018, Ukraine

Location

RCNECRCH Dept of Surgery, SHEI Ukr BSMU

Chernivtsi, Podolia Governorate, 58002, Ukraine

Location

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

Dnipropetrovsk, 49074, Ukraine

Location

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

Kharkiv, 61039, Ukraine

Location

CI Kherson Afanasii and Olha Tropiny City Clinical Hospital

Kherson, 73000, Ukraine

Location

M.V. Sklifosovskyi Poltava RCH Dept of Gastroenterology HSEIU UMSA

Poltava, 36011, Ukraine

Location

Private Small Enterprise Medical Center Pulse

Vinnytsia, 21001, Ukraine

Location

MCIC MC LLC Health Clinic

Vinnytsia, 21029, Ukraine

Location

Zaporizhzhia SMU

Zaporizhzhia, 69104, Ukraine

Location

LLC Diaservis

Zaporizhzhia, 69106, Ukraine

Location

Related Publications (2)

• Rubin DT, Dotan I, DuVall A, Bouhnik Y, Radford-Smith G, Higgins PDR, Mishkin DS, Arrisi P, Scalori A, Oh YS, Tole S, Chai A, Chamberlain-James K, Lacey S, McBride J, Panes J; HIBISCUS Study Group. Etrolizumab versus adalimumab or placebo as induction therapy for moderately to severely active ulcerative colitis (HIBISCUS): two phase 3 randomised, controlled trials. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):17-27. doi: 10.1016/S2468-1253(21)00338-1. Epub 2021 Nov 17.

  PMID: 34798036 DERIVED

• Sandborn WJ, Vermeire S, Tyrrell H, Hassanali A, Lacey S, Tole S, Tatro AR; Etrolizumab Global Steering Committee. Etrolizumab for the Treatment of Ulcerative Colitis and Crohn's Disease: An Overview of the Phase 3 Clinical Program. Adv Ther. 2020 Jul;37(7):3417-3431. doi: 10.1007/s12325-020-01366-2. Epub 2020 May 22.

  PMID: 32445184 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Adalimumab; etrolizumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 24, 2014
• Study Start: November 14, 2014
• Primary Completion: March 2, 2020
• Study Completion: May 25, 2020
• Last Updated: July 23, 2021
• Results First Posted: March 5, 2021

Record last verified: 2021-07

Locations

TU (4); CO (2); AU (5); AR (1); US (4); LA (3); MY (4); FR (1); NZ (5); BU (9); HU (1); PL (11); CR (2); RU (10); BR (5); UA (14); GR (1); LI (3); CZ (5)