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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03464136




Registration number
NCT03464136
Ethics application status
Date submitted
7/03/2018
Date registered
13/03/2018
Date last updated
8/07/2020

Titles & IDs
Public title
Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year
Scientific title
A Phase 3b, Multicenter, Randomized, Blinded, Active-Controlled Study to Compare the Efficacy and Safety of Ustekinumab to That of Adalimumab in the Treatment of Biologic Naïve Subjects With Moderately-to-Severely Active Crohn's Disease
Secondary ID [1] 0 0
2017-004209-41
Secondary ID [2] 0 0
CR108449
Universal Trial Number (UTN)
Trial acronym
SEAVUE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Placebo for Ustekinumab
Other interventions - Placebo for Adalimumab
Other interventions - Ustekinumab (6 mg/kg)
Other interventions - Ustekinumab (90 mg)
Other interventions - Adalimumab (40 mg)

Experimental: Group 1 (Ustekinumab) - Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram [mg/kg]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals.

Active Comparator: Group 2 (Adalimumab) - Participants will receive IV infusion of placebo for ustekinumab and 4 SC injections of adalimumab (each 40 mg, total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants will self-administer 1 SC injection of adalimumab 40 mg q2w.


Other interventions: Placebo for Ustekinumab
Participants will receive placebo as SC injection to blind adalimumab.

Other interventions: Placebo for Adalimumab
Participants will receive placebo as IV infusion to blind ustekinumab.

Other interventions: Ustekinumab (6 mg/kg)
Participants will receive ustekinumab 6 mg/kg (weight based dosing) as IV infusion.

Other interventions: Ustekinumab (90 mg)
Participants will self-administer SC injection of ustekinumab 90 mg.

Other interventions: Adalimumab (40 mg)
Participants will self-administer multiple SC injections of adalimumab (each 40 mg) and will receive total dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg q2w from Week 4 to 56.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Clinical Remission at Week 52 - Percentage of participants with clinical remission at Week 52 will be assessed. Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score of less than (<) 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). CDAI was assessed by collecting information on 8 different Crohn's disease-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being). A decrease in CDAI over time indicates improvement in disease activity.
Timepoint [1] 0 0
Week 52
Secondary outcome [1] 0 0
Percentage of Participants with Corticosteroid-free Remission at Week 52 (Major Secondary Endpoint) - Percentage of participants with Corticosteroid-free remission at Week 52 will be assessed. Corticosteroid-free remission is defined as CDAI score < 150 points at Week 52 and not taking any corticosteroids for at least 30 days prior to Week 52.
Timepoint [1] 0 0
Week 52
Secondary outcome [2] 0 0
Percentage of Participants with Clinical Response at Week 52 (Major Secondary Endpoint) - Percentage of participants with clinical response at Week 52 will be assessed. Clinical response at Week 52 is defined as a reduction from baseline in the CDAI score of greater than or equal (>=) 100 points.
Timepoint [2] 0 0
Week 52
Secondary outcome [3] 0 0
Percentage of Participants with Endoscopic Remission at Week 52 (Major Secondary Endpoint) - Percentage of participants with endoscopic remission at Week 52 will be assessed. Endoscopic remission is defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) score less than or equal to (<=) 3, or SES-CD =0 for participants who enter the study with an SES-CD =3 at Week 52. The SES-CD scoring system (ranges from 0 to 60) is considered in 5 segments of the bowel (the ileum, ascending colon, transverse colon, descending colon, and rectum) and includes 4 variables: ulcer size, extent of ulcerated surface, extent of affected surface, and stenosis.
Timepoint [3] 0 0
Week 52
Secondary outcome [4] 0 0
Percentage of Participants with Clinical Remission at Week 16 (Major Secondary Endpoint) - Percentage of participants with clinical remission (defined as CDAI < 150 points) at Week 16 will be assessed.
Timepoint [4] 0 0
Week 16
Secondary outcome [5] 0 0
Percentage of Participants with Clinical Remission (beginning at Week 8) through Week 52 - Percentage of participants with clinical remission (CDAI < 150 points) beginning at Week 8 will be measured at all postbaseline visits through Week 52.
Timepoint [5] 0 0
Weeks 8, 16, 24, 32, 40, 48, and 52
Secondary outcome [6] 0 0
Percentage of Participants with Clinical Response through Week 52 - Percentage of participants with clinical response (CDAI score decrease >=100 from baseline) will be assessed at all postbaseline visits through Week 52.
Timepoint [6] 0 0
Weeks 0, 2, 8, 16, 24, 32, 40, 48, and 52
Secondary outcome [7] 0 0
Change from Baseline in SES-CD Score at Week 52 - Change from baseline in SES-CD score will be measured at Week 52.
Timepoint [7] 0 0
Baseline, Week 52
Secondary outcome [8] 0 0
Change from Baseline in CRP concentration through Week 52 - Change from baseline in blood C-reactive protein (CRP) concentration will be assessed at all postbaseline visits through Week 52.
Timepoint [8] 0 0
Baseline (Week 0), Weeks 2, 8, 16, 24, 32, 40, 48, and 52
Secondary outcome [9] 0 0
Percentage of Participants with Normalization of CRP through Week 52 - Normalization of C-reactive protein is defined as C-reactive protein (CRP) <=3 milligram/liter (mg/L). Percentage of participants with normalization of CRP will be measured at all postbaseline visits through Week 52 among the participants having abnormal baseline CRP (> 3 mg/L).
Timepoint [9] 0 0
Weeks 0, 2, 8, 16, 24, 32, 40, 48, and 52
Secondary outcome [10] 0 0
Change from Baseline in Fecal Calprotectin Concentration through Week 52 - Change in fecal calprotectin concentration will be measured from baseline at all postbaseline visits through Week 52 (where fecal calprotectin assessed). Fecal calprotectin will be monitored as a non-invasive surrogate marker measured by enzyme-linked immunosorbent assays.
Timepoint [10] 0 0
Baseline (Week 0), Weeks 2, 8, 16, 24, 32, 40, 48, and 52
Secondary outcome [11] 0 0
Percentage of Participants with Adverse Events (AEs) - Percentage of participants with AE will be assessed. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Timepoint [11] 0 0
up to Week 52, and Week 76
Secondary outcome [12] 0 0
Percentage of Participants with Infections - Percentage of participants with infections will be assessed.
Timepoint [12] 0 0
up to Week 52 and Week 76
Secondary outcome [13] 0 0
Percentage of Participants with Serious Adverse Events (SAEs) - Percentage of participants with SAEs will be assessed. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Timepoint [13] 0 0
up to Week 52, and Week 76
Secondary outcome [14] 0 0
Percentage of Participants with Serious Infections - Percentage of participants with serious infections will be assessed.
Timepoint [14] 0 0
up to Week 52, and Week 76
Secondary outcome [15] 0 0
Percentage of Participants with Anti-drug Antibodies through Week 52 - Percentage of participants with anti-drug antibodies will be reported. Serum samples will be assessed for anti-drug antibodies. Anti-drug assays will be performed for ustekinumab and adalimumab.
Timepoint [15] 0 0
up to Week 52

Eligibility
Key inclusion criteria
- Has Crohn's Disease (CD) or fistulizing CD of at least 3 months' duration, with
colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography,
histology, and/or endoscopy

- Has moderately-to-severely active CD with a baseline Crohn's disease activity index
(CDAI) score of greater than or equal to (>=) 220 and less than or equal to (<=) 450

- Has one or more ulceration on screening ileocolonoscopy (which by definition, would
result in an Simple Endoscopic Score for Crohn's Disease [SES-CD] of at least 3)

- Has failed or was intolerant to conventional therapy (corticosteroids, azathioprine
[AZA], 6-mercaptopurine [6-MP] and/or methotrexate [MTX]) at adequate doses or is
corticosteroid dependent

- Has not previously received an approved biologic for Crohn's Disease (i.e.,
infliximab, adalimumab, certolizumab pegol, ustekinumab, natalizumab, vedolizumab or
approved biosimilars of these agents)

- Participants on oral corticosteroids (e.g., prednisone, budesonide) at a
prednisone-equivalent dose of <=40 or milligram/day (mg/day) or <=9 mg/day of
budesonide are budesonide <=9 mg/day are permitted if doses are stable for 3 weeks
prior to baseline

- Participants on AZA, 6-MP, or MTX at screening (or recently prior), must discontinue
these medications at least 3 weeks prior to baseline
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has complications of CD that are likely to require surgery or would confound the
ability to assess the effect of ustekinumab or adalimumab treatment using the CDAI,
such as: active stoma; short-gut syndrome and severe or symptomatic strictures or
stenosis

- Currently has, or is suspected to have, an abscess. Recent cutaneous and perianal
abscesses are not exclusionary if drained and adequately treated at least 3 weeks
prior to baseline, or 8 weeks prior for intra-abdominal abscesses, if there is no
anticipated need for any further surgery. Participants with active fistulas may be
included if there is no anticipation of a need for surgery and there are currently no
abscesses present

- Has had any kind of bowel resection within 6 months prior to baseline or other
intra-abdominal surgery or a hospital admission for bowel obstruction within 3 months
prior to baseline

- Has a stool culture or other examination positive for an enteric pathogen, including
Clostridium difficile toxin, in the last 4 months unless a repeat examination is
negative and there are no signs of ongoing infection with that pathogen

- Has received a Bacillus Calmette-Guerin (BCG) vaccination within 12 months or any
other live bacterial or live viral vaccination within 2 weeks of baseline

- Has a history of, or ongoing, chronic or recurrent infectious disease, including but
not limited to, chronic renal infection, chronic chest infection, recurrent urinary
tract infection (eg, recurrent pyelonephritis or chronic nonremitting cystitis), or
infected skin wounds or ulcers

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 administering the treatment/s
The people assessing the outcomes
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
Active, not recruiting
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)
Recruitment hospital [1] 0 0
Monash Health, Monash Medical Centre - Clayton
Recruitment hospital [2] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Mater Hospital Brisbane (Inflammatory Bowel Diseases) - South Brisbane
Recruitment hospital [4] 0 0
St John of God Subiaco Hospital - Subiaco
Recruitment hospital [5] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment postcode(s) [5] 0 0
5011 - Woodville South
Recruitment outside Australia
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Nis
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Taunton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Scientific Affairs, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare the efficacy of treatment with ustekinumab or
adalimumab in biologic naive participants with moderately-to-severely active Crohn's disease
(CD) who have previously failed or were intolerant to conventional therapy (corticosteroids
and/or immunomodulators, such as azathioprine, 6-mercaptopurine, or methotrexate), as
measured by clinical remission at one year.
Trial website
https://clinicaltrials.gov/show/NCT03464136
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Scientific Affairs, LLC Clinical Trial
Address 0 0
Janssen Scientific Affairs, LLC
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