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

NCT02163759 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GA289482013-004279-11
• Study Type: interventional
• Target: 358
• Locations: 14 countries
• Sites: 88

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 naÏve 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 (GA28949; NCT02171429) was independently conducted.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28948 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 as Compared With Adalimumab, as Determined by the MCS, GA28948 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, GA28948 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 MCS Endoscopy Subscore, GA28948 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 (88)

Rocky Mountain Gastroenterology Associates, P.L.L.C.; Gastroenterology

Lakewood, Colorado, 80215, United States

Location

Center for Advanced Gastroenterology

Maitland, Florida, 32751, United States

Location

Gastroenterology Group of Naples

Naples, Florida, 34102, United States

Location

Gastroenterology Associates of Central Georgia

Macon, Georgia, 31201, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Center for Digestive Health

Troy, Michigan, 48098, United States

Location

Huron Gastroenterology Associates

Ypsilanti, Michigan, 48197, United States

Location

Wellness Clinical Research Center

San Antonio, Texas, 78232, United States

Location

Tyler Research Institute, LLC

Tyler, Texas, 75701, United States

Location

Instituto Medico DAMIC

Córdoba, X5003DCE, Argentina

Location

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, 2200, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Mater Hospital Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

CCBR - Brasilia

Brasília, Federal District, 70200-730, Brazil

Location

Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda

Goiânia, Goiás, 74535-170, Brazil

Location

Hospital Felicio Rocho

Belo Horizonte, Minas Gerais, 30110-068, Brazil

Location

Hospital Universitario Clementino Fraga Filho - UFRJ

Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu

Botucatu, São Paulo, 18618-970, Brazil

Location

UMHAT "Sv. Ivan Rilski", EAD

Sofia, 1431, Bulgaria

Location

UMHAT Tsaritsa Yoanna - ISUL, EAD

Sofia, 1527, Bulgaria

Location

MC Medica Plus

Veliko Tarnovo, 5000, Bulgaria

Location

OÜ Innomedica

Tallinn, 10117, Estonia

Location

East Tallinn Central Hospital

Tallinn, 10138, Estonia

Location

West Tallinn Central Hospital

Tallinn, 10617, Estonia

Location

North Estonia Medical Centre Foundation

Tallinn, 13419, Estonia

Location

Tartu University Hospital

Tartu, 51014, Estonia

Location

Hôpital Beaujon

Clichy, 92110, France

Location

CHU Nice - Hopital de l'Archet 2

Nice, 06202, France

Location

University of Hong Kong

Hong Kong, Hong Kong

Location

Centro Integral en Reumatología S.A. de C.V. (CIRSA)

Guadalajara, Jalisco, 44160, Mexico

Location

Accelerium S. de R.L. de C.V.

Monterrey, 64000, Mexico

Location

Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León

Monterrey, 64460, Mexico

Location

Centrum Medyczne Sw. Lukasza

Częstochowa, 42-202, Poland

Location

7 Szpital Marynarki Wojennej z Przychodnia SPZOZ im. W. Lasinskiego

Gdansk, 80-305, Poland

Location

NZOZ Centrum Medyczne ProMiMed

Krakow, 31-637, Poland

Location

AppleTreeClinics Sp. z o.o.

Lodz, 90-349, Poland

Location

Med-Gastr Przychodnia Specjalistyczna

Lodz, 91-034, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska

Lublin, 20-015, Poland

Location

GASTROMED Sp. z o.o.

Lublin, 20-582, Poland

Location

Wojewodzki Specjalistyczny Szpital w Olsztynie

Olsztyn, 10-561, Poland

Location

SOLUMED Centrum Medyczne

Poznan, 60-529, Poland

Location

Specjalistyczna Praktyka Lekarska Dr med. Marek Horynski; endoskopia

Sopot, 81-756, Poland

Location

Twoja Przychodnia-Szczecinskie Centrum Medyczne

Szczecin, 71-434, Poland

Location

Centrum Zdrowia MDM

Warsaw, 00-631, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

EMC Instytut Medyczny S.A.

Wroclaw, 50-220, Poland

Location

PlanetMed

Wroclaw, 52-210, Poland

Location

Yusupov Hospital

Moskva, Adygeya Republic, 127015, Russia

Location

SPb SBIH "City Multy-field Hospital # 2"; Intensive Pulmonology and Thoracal Surgery

Saint Petersburg, Sankt-Peterburg, 194354, Russia

Location

Baltic Medicine

Saint Petersburg, Sankt-Peterburg, 194356, Russia

Location

Medical and Sanitary Division of Severstal

Cherepovets, Vologda Oblast, 162600, Russia

Location

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

Barnaul, 656038, Russia

Location

FSBIH Central Clinical Hospital of RAS

Moscow, 119333, Russia

Location

FSBI "State Scientific Centre of Coloproctology" of the MoH of RF; Gastroenterology

Moscow, 123154, Russia

Location

SBHI of NN region "RCH of NN n.a. N.A.Semashko"

Nizhny Novgorod, 603126, Russia

Location

SBEI of HPE "Omsk SMA" Ministry of healthcare of RF"

Omsk, 644043, Russia

Location

SEIHPE "Rostov SMU of MoH of RF"

Rostov-on-Don, 344022, Russia

Location

FSMEI HPE "Military Medical Academy n.a. S.M.Kirov"of Minist

Saint Petersburg, 194044, Russia

Location

City Hospital #26

Saint Petersburg, 196247, Russia

Location

LLC International Medical Centre "SOGAZ"

Saint Petersburg, 198035, Russia

Location

Stavropol Regional Clinical Diagnostic Consultative Center

Stavropol, 355017, Russia

Location

Clinical Center Zvezdara

Belgrade, 11000, Serbia

Location

Military Medical Academy

Belgrade, 11040, Serbia

Location

Clinical Center Bezanijska Kosa

Belgrade, 11070, Serbia

Location

Clinical Center Zemun

Belgrade, 11080, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

General Hospital "Djordje Joanovic"; Gastroenterology

Zrenjanin, 23000, Serbia

Location

Fakultna nemocnica s poliklinikou F.D. Roosevelta

Banská Bystrica, 975 17, Slovakia

Location

Nemocnica A.Lena Humenne, n.o.

Humenné, 066 01, Slovakia

Location

KM Management spol. s r.o.

Nitra, 94901, Slovakia

Location

Gastro I, s.r.o.

Prešov, 080 01, Slovakia

Location

Svet zdravia a.s.

Rimavská Sobota, 979 01, Slovakia

Location

Accout Center s.r.o.

Šahy, 936 01, Slovakia

Location

CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC

Kharkiv, Kharkiv Governorate, 61037, Ukraine

Location

Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital

Kharkiv, Kharkiv Governorate, 61058, Ukraine

Location

Communal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital

Kyiv, Kharkiv Governorate, 04107, Ukraine

Location

Medical Center of Limited Liability Company Medical Clinic Blagomed

Kyiv, KIEV Governorate, 1023, Ukraine

Location

CI of Kyiv RC Regional Clinical Hospital #2

Kyiv, KIEV Governorate, 4073, Ukraine

Location

CI City Hospital #1

Zaporizhzhia, Tavria Okruha, 69104, Ukraine

Location

RCI Chernivtsi RCH Gastroenterology Bukovinsky SMU

Chernivtsi, 58002, Ukraine

Location

CHI Kharkiv City Clinical Hospital #13

Kharkiv, 61124, Ukraine

Location

CNI Consultative and Diagnostic Center of Desnianskyi District of Kyiv

Kyiv, 02232, Ukraine

Location

M.V. Sklifosovskyi Poltava RCH Outpatient UMSA HSEIU Ukrainian Medical Stomatological Academy

Poltava, 36011, Ukraine

Location

CI City Hospital #7

Zaporizhzhia, 69118, 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 12, 2014
• First Posted: June 16, 2014
• Study Start: November 4, 2014
• Primary Completion: February 19, 2020
• Study Completion: March 19, 2020
• Last Updated: July 23, 2021
• Results First Posted: April 5, 2021

Record last verified: 2021-07

Locations

AU (6); US (9); HK (1); SE (6); BR (6); RU (14); FR (2); SL (6); AR (1); ME (3); UA (11); BU (3); ES (5); PL (15)