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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02163759




Registration number
NCT02163759
Ethics application status
Date submitted
12/06/2014
Date registered
16/06/2014
Date last updated
30/03/2020

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 (Study #1)
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
2013-004279-11
Secondary ID [2] 0 0
GA28948
Universal Trial Number (UTN)
Trial acronym
HIBISCUS I
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

Active Comparator: Adalimumab + Etrolizumab Placebo - Participants will receive adalimumab up to Week 8 and placebo matching to etrolizumab up to Week 12.

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

Placebo Comparator: Etrolizumab Placebo + Adalimumab Placebo - Participants will receive placebo matching to 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).

Other interventions: Etrolizumab Placebo
Placebo matching to etrolizumab will be administered SC Q4W.

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 With Induction of Remission With Etrolizumab Compared With Placebo at Week 10, as Determined by the Mayo Clinic Score (MCS)
Timepoint [1] 0 0
Week 10
Secondary outcome [1] 0 0
Percentage of Participants With Induction of Remission With Etrolizumab Compared With Adalimumab at Week 10, as Determined by the MCS
Timepoint [1] 0 0
Week 10
Secondary outcome [2] 0 0
Percentage of Participants With Induction of Clinical Remission at Week 10, as Determined by the MCS
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
Timepoint [3] 0 0
Week 10
Secondary outcome [4] 0 0
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the Mayo Endoscopic Subscore
Timepoint [4] 0 0
Week 10
Secondary outcome [5] 0 0
Percentage of Participants With Endoscopic Remission at Week 10, as Determined by the Mayo Endoscopic Subscore
Timepoint [5] 0 0
Week 10
Secondary outcome [6] 0 0
Percentage of Participants who Achieve Remission at Week 10 and who Maintained Remission to Week 14, as Determined by the MCS
Timepoint [6] 0 0
Week 10 and 14
Secondary outcome [7] 0 0
Percentage of Participants With Histological Remission at Week 10, as Determined by the Nancy Histological Subscore
Timepoint [7] 0 0
Week 10
Secondary outcome [8] 0 0
Change from Baseline in MCS Rectal Bleeding Subscore at Week 6
Timepoint [8] 0 0
Baseline, Week 6
Secondary outcome [9] 0 0
Change from Baseline in MCS Stool Frequency Subscore at Week 6
Timepoint [9] 0 0
Baseline, Week 6
Secondary outcome [10] 0 0
Change From Baseline in Ulcerative Colitis (UC) Bowel Movement Signs and Symptoms at Week 10, as Assessed by UC-Participant-Reported Outcome Signs and Symptoms (PRO/SS)
Timepoint [10] 0 0
Baseline, Week 10
Secondary outcome [11] 0 0
Change From Baseline in UC Abdominal Symptoms at Week 10, as Assessed by UC-PRO/SS
Timepoint [11] 0 0
Baseline, Week 10
Secondary outcome [12] 0 0
Change From Baseline in Health-Related Quality of Life (QOL) at Week 10, as Assessed by Overall Inflammatory Bowel Disease Questionnaire (IBDQ)
Timepoint [12] 0 0
Baseline, Week 10
Secondary outcome [13] 0 0
Pharmacokinetics of Etrolizumab: Serum Concentration
Timepoint [13] 0 0
Pre-dose (0 hour) on Day 1, Week 10, Week 14, early termination/end of safety follow-up (up to Week 26)
Secondary outcome [14] 0 0
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)
Timepoint [14] 0 0
Baseline up to end of study (up to Week 26)
Secondary outcome [15] 0 0
Percentage of Participants With at Least One Serious Adverse Event
Timepoint [15] 0 0
Baseline up to end of study (up to Week 26)
Secondary outcome [16] 0 0
Percentage of Participants With Adverse Events Leading To Study Drug Discontinuation
Timepoint [16] 0 0
Baseline up to end of study (up to Week 26)
Secondary outcome [17] 0 0
Percentage of Participants With Infection-Related Adverse Events by Severity, According to NCI CTCAE v4.0
Timepoint [17] 0 0
Baseline up to end of study (up to Week 26)
Secondary outcome [18] 0 0
Percentage of Participants With Serious Infection-Related Adverse Events
Timepoint [18] 0 0
Baseline up to end of study (up to Week 26)
Secondary outcome [19] 0 0
Percentage of Participants With Injection-Site Reactions by Severity, According to NCI CTCAE v4.0
Timepoint [19] 0 0
Baseline up to end of study (up to Week 26)
Secondary outcome [20] 0 0
Percentage of Participants With Hypersensitivity Reaction Events by Severity, According to NCI CTCAE v4.0
Timepoint [20] 0 0
Baseline up to end of study (up to Week 26)
Secondary outcome [21] 0 0
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Etrolizumab
Timepoint [21] 0 0
Pre-dose (0 hour) on Day 1, Week 4, Week 10, Week 14, early termination/end of safety follow-up (up to Week 26)
Secondary outcome [22] 0 0
Percentage of Participants With Laboratory Abnormalities - Laboratory parameters for hematology, blood chemistry, and urinalysis will be measured compared with a standard reference range. Values outside the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result must be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment.
Timepoint [22] 0 0
Baseline (Day 1), Week 10, and any unscheduled visits or early withdrawal from treatment, up to end of study (up to Week 26)

Eligibility
Key inclusion criteria
- Diagnosis of 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
Gender
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 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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [6] 0 0
Royal Melbourne Hospital; Department of Colorectal Medicine and Genetics - Parkville
Recruitment hospital [7] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2200 - Bankstown
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Cordoba
Country [9] 0 0
Brazil
State/province [9] 0 0
DF
Country [10] 0 0
Brazil
State/province [10] 0 0
GO
Country [11] 0 0
Brazil
State/province [11] 0 0
MG
Country [12] 0 0
Brazil
State/province [12] 0 0
RJ
Country [13] 0 0
Brazil
State/province [13] 0 0
RS
Country [14] 0 0
Brazil
State/province [14] 0 0
SP
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Veliko Tarnovo
Country [17] 0 0
Estonia
State/province [17] 0 0
Tallinn
Country [18] 0 0
Estonia
State/province [18] 0 0
Tartu
Country [19] 0 0
France
State/province [19] 0 0
Clichy cedex
Country [20] 0 0
France
State/province [20] 0 0
Nice
Country [21] 0 0
France
State/province [21] 0 0
Saint Etienne
Country [22] 0 0
Hong Kong
State/province [22] 0 0
Hong Kong
Country [23] 0 0
Mexico
State/province [23] 0 0
Jalisco
Country [24] 0 0
Mexico
State/province [24] 0 0
Nuevo LEON
Country [25] 0 0
Mexico
State/province [25] 0 0
Monterrey
Country [26] 0 0
Poland
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Czestochowa
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Poland
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Gdansk
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Poland
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Krakow
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Poland
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Lodz
Country [30] 0 0
Poland
State/province [30] 0 0
Lublin
Country [31] 0 0
Poland
State/province [31] 0 0
Olsztyn
Country [32] 0 0
Poland
State/province [32] 0 0
Poznan
Country [33] 0 0
Poland
State/province [33] 0 0
Sopot
Country [34] 0 0
Poland
State/province [34] 0 0
Szczecin
Country [35] 0 0
Poland
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Warszawa
Country [36] 0 0
Poland
State/province [36] 0 0
Wroclaw
Country [37] 0 0
Poland
State/province [37] 0 0
Lódz
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Adygeja
Country [39] 0 0
Russian Federation
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Leningrad
Country [40] 0 0
Russian Federation
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Sankt Petersburg
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Russian Federation
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Vologda
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Russian Federation
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Barnaul
Country [43] 0 0
Russian Federation
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Moscow
Country [44] 0 0
Russian Federation
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Nizhny Novgorod
Country [45] 0 0
Russian Federation
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Omsk
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Russian Federation
State/province [46] 0 0
Rostov-on-Don
Country [47] 0 0
Russian Federation
State/province [47] 0 0
St Petersburg
Country [48] 0 0
Russian Federation
State/province [48] 0 0
St-Petersburg
Country [49] 0 0
Russian Federation
State/province [49] 0 0
St. Petersburg
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Stavropol
Country [51] 0 0
Serbia
State/province [51] 0 0
Belgrade
Country [52] 0 0
Serbia
State/province [52] 0 0
Kragujevac
Country [53] 0 0
Serbia
State/province [53] 0 0
Zrenjanin
Country [54] 0 0
Slovakia
State/province [54] 0 0
Banska Bystrica
Country [55] 0 0
Slovakia
State/province [55] 0 0
Humenné
Country [56] 0 0
Slovakia
State/province [56] 0 0
Nitra
Country [57] 0 0
Slovakia
State/province [57] 0 0
Presov
Country [58] 0 0
Slovakia
State/province [58] 0 0
Rimavska Sobota
Country [59] 0 0
Slovakia
State/province [59] 0 0
Ĺ ahy
Country [60] 0 0
Ukraine
State/province [60] 0 0
Kharkiv Governorate
Country [61] 0 0
Ukraine
State/province [61] 0 0
KIEV Governorate
Country [62] 0 0
Ukraine
State/province [62] 0 0
Tavria Okruha
Country [63] 0 0
Ukraine
State/province [63] 0 0
Chernivtsi
Country [64] 0 0
Ukraine
State/province [64] 0 0
Kharkiv
Country [65] 0 0
Ukraine
State/province [65] 0 0
Kyiv
Country [66] 0 0
Ukraine
State/province [66] 0 0
Poltava
Country [67] 0 0
Ukraine
State/province [67] 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
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 UC who are naIve to TNF inhibitors and
refractory to or intolerant of prior immunosuppressant and/or corticosteroid treatment.
Trial website
https://clinicaltrials.gov/show/NCT02163759
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

Summary results
Other publications