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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02171429




Registration number
NCT02171429
Ethics application status
Date submitted
20/06/2014
Date registered
24/06/2014
Date last updated
23/07/2021

Titles & IDs
Public title
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
Scientific title
Phase III, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy (Induction of Remission) and Safety of Etrolizumab Compared With Adalimumab and Placebo in Patients With Moderate to Severe Ulcerative Colitis Who Are Naive to TNF Inhibitors
Secondary ID [1] 0 0
2013-004277-27
Secondary ID [2] 0 0
GA28949
Universal Trial Number (UTN)
Trial acronym
HIBISCUS II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Adalimumab
Other interventions - Adalimumab Placebo
Treatment: Drugs - Etrolizumab
Other interventions - Etrolizumab Placebo

Placebo comparator: Placebo - Participants will receive placebo matching to etrolizumab up to Week 12 and placebo matching to adalimumab up to Week 8.

Active comparator: Adalimumab - Participants will receive adalimumab up to Week 8 and placebo matching to etrolizumab up to Week 12.

Experimental: Etrolizumab - Participants will receive etrolizumab up to Week 12 and placebo matching to adalimumab up to Week 8.


Treatment: Drugs: Adalimumab
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.

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

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

Other interventions: Etrolizumab Placebo
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 \[clinical remitters only\]).
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants in Remission at Week 10 With Etrolizumab Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28949 Population
Timepoint [1] 0 0
Week 10
Secondary outcome [1] 0 0
Percentage of Participants in Remission at Week 10 With Etrolizumab Compared With Adalimumab, as Determined by the MCS, GA28949 Population
Timepoint [1] 0 0
Week 10
Secondary outcome [2] 0 0
Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population
Timepoint [2] 0 0
Week 10
Secondary outcome [3] 0 0
Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28949 Population
Timepoint [3] 0 0
Week 10
Secondary outcome [4] 0 0
Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population
Timepoint [4] 0 0
Week 10
Secondary outcome [5] 0 0
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the Mayo Endoscopy Subscore, GA28949 Population
Timepoint [5] 0 0
Week 10
Secondary outcome [6] 0 0
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS Endoscopy Subscore, GA28948 & GA28949 Pooled Population
Timepoint [6] 0 0
Week 10
Secondary outcome [7] 0 0
Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28949 Population
Timepoint [7] 0 0
Week 10
Secondary outcome [8] 0 0
Percentage of Participants in Endoscopic Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS Endoscopy Subscore, GA28948 & GA28949 Pooled Population
Timepoint [8] 0 0
Week 10
Secondary outcome [9] 0 0
Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28949 Population
Timepoint [9] 0 0
Week 10
Secondary outcome [10] 0 0
Percentage of Participants With Histologic Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the Nancy Histological Index, GA28948 & GA28949 Pooled Population
Timepoint [10] 0 0
Week 10
Secondary outcome [11] 0 0
Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28949 Population
Timepoint [11] 0 0
Baseline, Week 6
Secondary outcome [12] 0 0
Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population
Timepoint [12] 0 0
Baseline, Week 6
Secondary outcome [13] 0 0
Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28949 Population
Timepoint [13] 0 0
Baseline, Week 6
Secondary outcome [14] 0 0
Change From Baseline in the MCS Stool Frequency Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population
Timepoint [14] 0 0
Baseline, Week 6
Secondary outcome [15] 0 0
Change From Baseline in Ulcerative Colitis (UC) Bowel Movement Signs and Symptoms at Week 10, as Assessed by the UC Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS), GA28949 Population
Timepoint [15] 0 0
Baseline, Week 10
Secondary outcome [16] 0 0
Change From Baseline in Ulcerative Colitis Bowel Movement Signs and Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population
Timepoint [16] 0 0
Baseline, Week 10
Secondary outcome [17] 0 0
Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28949 Population
Timepoint [17] 0 0
Baseline, Week 10
Secondary outcome [18] 0 0
Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population
Timepoint [18] 0 0
Baseline, Week 10
Secondary outcome [19] 0 0
Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28949 Population
Timepoint [19] 0 0
Week 10
Secondary outcome [20] 0 0
Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28949 Population
Timepoint [20] 0 0
Weeks 10 and 14
Secondary outcome [21] 0 0
Change From Baseline in Health-Related Quality of Life at Week 10, as Assessed by the Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score, GA28949 Population
Timepoint [21] 0 0
Baseline, Week 10
Secondary outcome [22] 0 0
Pharmacokinetics of Etrolizumab: Serum Concentration, GA28949 Population
Timepoint [22] 0 0
Weeks 10 and 14
Secondary outcome [23] 0 0
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population
Timepoint [23] 0 0
From Baseline until the end of study (up to 26 weeks)
Secondary outcome [24] 0 0
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population
Timepoint [24] 0 0
From Baseline up to Week 10
Secondary outcome [25] 0 0
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population
Timepoint [25] 0 0
From Baseline up to Week 10
Secondary outcome [26] 0 0
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population
Timepoint [26] 0 0
Pre-dose (0 hour) on Day 1 and Week 4, Week 10, Week 14, and early termination/end of safety follow-up (up to 26 weeks)

Eligibility
Key inclusion criteria
* 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
* 5-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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria Related to Inflammatory Bowel Disease:

* 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

Exclusion Criteria Related to Prior or Concomitant Therapy:

* 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
* Use of intravenous (IV) steroids within 30 days prior to screening with the exception of a single administration of IV steroid
* Use of agents that deplete B or T cells
* Use of anakinra, abatacept, cyclosporine, sirolimus, or mycophenolate mofetil (MMF) within 4 weeks prior to randomization
* Chronic nonsteroidal anti-inflammatory drug (NSAID) use
* Patients who are currently using anticoagulants including, but not limited to, warfarin, heparin, enoxaparin, dabigatran, apixaban, rivaroxaban
* Patients who have received treatment with corticosteroid enemas/suppositories and/or topical (rectal) 5-ASA preparations within 2 weeks prior to randomization
* Apheresis (i.e., Adacolumn apheresis) within 2 weeks prior to randomization
* Received any investigational treatment including investigational vaccines within 5 half lives of the investigational product or 28 days after the last dose, whichever is greater, prior to randomization
* History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies, fusion proteins, or murine proteins or hypersensitivity to etrolizumab (active drug substance) or any of the excipients (L histidine, L-arginine, succinic acid, polysorbate 20)
* Patients administered tube feeding, defined formula diets, or parenteral alimentation/nutrition who have not discontinued these treatments within 3 weeks prior to randomization

Exclusion Criteria Related to General Safety:

* Pregnant or lactating
* Lack of peripheral venous access
* Hospitalization (other than for elective reasons) during the screening period
* Significant uncontrolled comorbidity, such as cardiac (e.g., moderate to severe heart failure New York Heart Association Class III/IV), pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders
* Neurological conditions or diseases that may interfere with monitoring for PML
* History of demyelinating disease
* Clinically significant abnormalities on screening neurologic examination (PML Objective Checklist)
* Clinically significant abnormalities on the screening PML Subjective Checklist
* History of alcohol, drug, or chemical abuse less than 6 months prior to screening
* Conditions other than UC that could require treatment with >10 mg/day of prednisone (or equivalent) during the course of the study
* History of cancer, including hematologic malignancy, solid tumors, and carcinoma in situ, within 5 years before screening

Exclusion Criteria Related to Infection Risk

* Congenital or acquired immune deficiency
* Patients must undergo screening for HIV and test positive for preliminary and confirmatory tests
* Positive hepatitis C virus (HCV) antibody test result
* Positive hepatitis B virus (HBV) antibody test result
* Evidence of or treatment for Clostridium difficile (as assessed by C. difficile toxin testing) within 60 days prior to randomization or other intestinal pathogens (as assessed by stool culture and ova and parasite evaluation) within 30 days prior to randomization
* Evidence of or treatment for clinically significant cytomegalovirus (CMV) colitis (based on the investigator's judgment) within 60 days prior to randomization
* History of active or latent TB
* History of recurrent opportunistic infections and/or history of severe disseminated viral infections
* Any serious opportunistic infection within the last 6 months prior to screening
* Any current or recent signs or symptoms (within 4 weeks before screening and during screening) of infection
* Any major episode of infection requiring treatment with IV antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior to screening
* Received a live attenuated vaccine within 4 weeks prior to randomization
* History of organ transplant

Exclusion Criteria Related to Laboratory Abnormalities (at Screening)

* Serum creatinine >2 x upper limit of normal (ULN)
* ALT or AST >3 x ULN or alkaline phosphatase >3 x ULN or total bilirubin >2.5 x ULN
* Platelet count <100,000/uL
* Hemoglobin <8 g/dL
* Absolute neutrophil count <1500/uL
* Absolute lymphocyte count <500/uL

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/11/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/05/2020
Sample size
Target
Accrual to date
Final
358
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [5] 0 0
Footscray Hospital; Gastroenterology - Footscray
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3011 - Footscray
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
Argentina
State/province [4] 0 0
Mar del Plata
Country [5] 0 0
Brazil
State/province [5] 0 0
BA
Country [6] 0 0
Brazil
State/province [6] 0 0
CE
Country [7] 0 0
Brazil
State/province [7] 0 0
PR
Country [8] 0 0
Brazil
State/province [8] 0 0
RS
Country [9] 0 0
Brazil
State/province [9] 0 0
SP
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Dupnitsa
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Pleven
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Ruse
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Sliven
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Sofia
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Stara Zagora
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Varna
Country [17] 0 0
Colombia
State/province [17] 0 0
Cali
Country [18] 0 0
Colombia
State/province [18] 0 0
Medellin
Country [19] 0 0
Croatia
State/province [19] 0 0
Osijek
Country [20] 0 0
Croatia
State/province [20] 0 0
Zagreb
Country [21] 0 0
Czechia
State/province [21] 0 0
Hradec Kralove
Country [22] 0 0
Czechia
State/province [22] 0 0
Olomouc
Country [23] 0 0
Czechia
State/province [23] 0 0
Pardubice
Country [24] 0 0
Czechia
State/province [24] 0 0
Praha 7
Country [25] 0 0
France
State/province [25] 0 0
Pierre Benite
Country [26] 0 0
Greece
State/province [26] 0 0
Herakleion
Country [27] 0 0
Hungary
State/province [27] 0 0
Gyor
Country [28] 0 0
Latvia
State/province [28] 0 0
Daugavpils
Country [29] 0 0
Latvia
State/province [29] 0 0
Riga
Country [30] 0 0
Lithuania
State/province [30] 0 0
Kaunas
Country [31] 0 0
Lithuania
State/province [31] 0 0
Klaipeda
Country [32] 0 0
Lithuania
State/province [32] 0 0
Vilnius
Country [33] 0 0
Malaysia
State/province [33] 0 0
Kota Bahru
Country [34] 0 0
Malaysia
State/province [34] 0 0
Kuala Lumpur
Country [35] 0 0
Malaysia
State/province [35] 0 0
Pahang
Country [36] 0 0
New Zealand
State/province [36] 0 0
Auckland
Country [37] 0 0
New Zealand
State/province [37] 0 0
Dunedin
Country [38] 0 0
New Zealand
State/province [38] 0 0
Hamilton
Country [39] 0 0
New Zealand
State/province [39] 0 0
Takapuna
Country [40] 0 0
New Zealand
State/province [40] 0 0
Tauranga
Country [41] 0 0
Poland
State/province [41] 0 0
Katowice
Country [42] 0 0
Poland
State/province [42] 0 0
Ksawerow
Country [43] 0 0
Poland
State/province [43] 0 0
Nowy Targ
Country [44] 0 0
Poland
State/province [44] 0 0
Rzeszow
Country [45] 0 0
Poland
State/province [45] 0 0
Rzeszów
Country [46] 0 0
Poland
State/province [46] 0 0
Szczecin
Country [47] 0 0
Poland
State/province [47] 0 0
Warszawa
Country [48] 0 0
Poland
State/province [48] 0 0
Wroclaw
Country [49] 0 0
Poland
State/province [49] 0 0
Lódz
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Sankt Petersburg
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Barnaul
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Irkutsk
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Novosibirsk
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Omsk
Country [55] 0 0
Russian Federation
State/province [55] 0 0
St. Petersburg
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Stavropol
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Voronezh
Country [58] 0 0
Turkey
State/province [58] 0 0
Ankara
Country [59] 0 0
Turkey
State/province [59] 0 0
Gaziantep
Country [60] 0 0
Turkey
State/province [60] 0 0
Istanbul
Country [61] 0 0
Turkey
State/province [61] 0 0
Kocaeli
Country [62] 0 0
Ukraine
State/province [62] 0 0
Kharkiv Governorate
Country [63] 0 0
Ukraine
State/province [63] 0 0
KIEV Governorate
Country [64] 0 0
Ukraine
State/province [64] 0 0
Podolia Governorate
Country [65] 0 0
Ukraine
State/province [65] 0 0
Dnipropetrovsk
Country [66] 0 0
Ukraine
State/province [66] 0 0
Kharkiv
Country [67] 0 0
Ukraine
State/province [67] 0 0
Kherson
Country [68] 0 0
Ukraine
State/province [68] 0 0
Poltava
Country [69] 0 0
Ukraine
State/province [69] 0 0
Vinnytsia
Country [70] 0 0
Ukraine
State/province [70] 0 0
Zaporizhzhia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02171429