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Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year (SEAVUE)

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ClinicalTrials.gov Identifier: NCT03464136
Recruitment Status : Recruiting
First Posted : March 13, 2018
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Scientific Affairs, LLC

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.

Condition or disease Intervention/treatment Phase
Crohn Disease Biological: Placebo for Ustekinumab Biological: Placebo for Adalimumab Biological: Ustekinumab (6 mg/kg) Biological: Ustekinumab (90 mg) Biological: Adalimumab (40 mg) Phase 3

Detailed Description:
This study compares the safety and efficacy of ustekinumab versus adalimumab. It will consist of screening (within 1- 5 weeks prior to Week 0), treatment phase (Weeks 0 to 52), and follow-up phase (up to Week 76). The primary hypothesis is that ustekinumab is superior to adalimumab as measured by clinical remission after one year of treatment. Study assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy; CD-related healthcare utilization; patient-reported outcomes (PROs); laboratory evaluations; biomarkers; review of concomitant medications and adverse events (AEs); and evaluation of serum concentrations of study agent as well as development of antibodies to study agent. All participants will randomly be assigned to receive either ustekinumab or adalimumab. No participants will be treated with placebo only.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : March 29, 2018
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : May 20, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
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.
Biological: Placebo for Ustekinumab
Participants will receive placebo as SC injection to blind adalimumab.

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

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

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

Biological: 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.
Other Name: Humira




Primary Outcome Measures :
  1. Percentage of Participants with Clinical Remission at Week 52 [ Time Frame: 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.


Secondary Outcome Measures :
  1. Percentage of Participants with Corticosteroid-free Remission at Week 52 (Major Secondary Endpoint) [ Time Frame: Week 52 ]
    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.

  2. Percentage of Participants with Clinical Response at Week 52 (Major Secondary Endpoint) [ Time Frame: Week 52 ]
    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.

  3. Percentage of Participants with Endoscopic Remission at Week 52 (Major Secondary Endpoint) [ Time Frame: Week 52 ]
    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.

  4. Percentage of Participants with Clinical Remission at Week 16 (Major Secondary Endpoint) [ Time Frame: Week 16 ]
    Percentage of participants with clinical remission (defined as CDAI < 150 points) at Week 16 will be assessed.

  5. Percentage of Participants with Clinical Remission (beginning at Week 8) through Week 52 [ Time Frame: Weeks 8, 16, 24, 32, 40, 48, and 52 ]
    Percentage of participants with clinical remission (CDAI < 150 points) beginning at Week 8 will be measured at all postbaseline visits through Week 52.

  6. Percentage of Participants with Clinical Response through Week 52 [ Time Frame: Weeks 0, 2, 8, 16, 24, 32, 40, 48, and 52 ]
    Percentage of participants with clinical response (CDAI score decrease >=100 from baseline) will be assessed at all postbaseline visits through Week 52.

  7. Change from Baseline in SES-CD Score at Week 52 [ Time Frame: Baseline, Week 52 ]
    Change from baseline in SES-CD score will be measured at Week 52.

  8. Change from Baseline in CRP concentration through Week 52 [ Time Frame: Baseline (Week 0), Weeks 2, 8, 16, 24, 32, 40, 48, and 52 ]
    Change from baseline in blood C-reactive protein (CRP) concentration will be assessed at all postbaseline visits through Week 52.

  9. Percentage of Participants with Normalization of CRP through Week 52 [ Time Frame: Weeks 0, 2, 8, 16, 24, 32, 40, 48, and 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).

  10. Change from Baseline in Fecal Calprotectin Concentration through Week 52 [ Time Frame: Baseline (Week 0), Weeks 2, 8, 16, 24, 32, 40, 48, and 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.

  11. Percentage of Participants with Adverse Events (AEs) [ Time Frame: up to Week 52, and Week 76 ]
    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.

  12. Percentage of Participants with Infections [ Time Frame: up to Week 52 and Week 76 ]
    Percentage of participants with infections will be assessed.

  13. Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: up to Week 52, and Week 76 ]
    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.

  14. Percentage of Participants with Serious Infections [ Time Frame: up to Week 52, and Week 76 ]
    Percentage of participants with serious infections will be assessed.

  15. Percentage of Participants with Anti-drug Antibodies through Week 52 [ Time Frame: up to 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03464136


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

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Sponsors and Collaborators
Janssen Scientific Affairs, LLC
Investigators
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Study Director: Janssen Scientific Affairs, LLC Clinical Trial Janssen Scientific Affairs, LLC

Additional Information:
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Responsible Party: Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier: NCT03464136     History of Changes
Other Study ID Numbers: CR108449
2017-004209-41 ( EudraCT Number )
CNTO1275CRD3007 ( Other Identifier: Janssen Scientific Affairs, LLC )
First Posted: March 13, 2018    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Adalimumab
Ustekinumab
Anti-Inflammatory Agents
Antirheumatic Agents
Dermatologic Agents