chronic inflammation of the intestinal wall enteritis regionalis
Conditions
Interventions
Study visits are to occur at Screening (within 1- 5 weeks prior to Week 0), and
Weeks 0, 2, 8, 16, 24, 32, 40, 48, 52 (primary endpoint), and 56, with a final
follow-up telephone call (or on-site vi
ustekinumab 90 mg
will be administered every eighth week after Week 0, with placebo
for adalimumab administered at the other designated q2w dosing intervals
- Group 2 (adalimumab): 1 SC injection o
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: A subject must meet the following criteria to be enrolled: 1. Be male or female (according to their reproductive organs and functions assigned by chromosomal complement) *18 years of age 2. Has 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 3. Has moderately-to-severely active CD with a baseline Crohn*s disease activity index (CDAI) score of * 220 and * 450 4. 4. Has one or more ulceration on screening ileocolonoscopy (which, by definition, would result in an SES-CD of at least 3). Note: If a subject had an ileocolonoscopy but then screen failed for another reason, if he/she is rescreened within 3 months, then that ileocolonoscopy is sufficient for inclusion if all other entry criteria are met 5. Meets the following requirements for prior or current medications for CD: a) Has failed conventional therapy: i) Is currently receiving corticosteroids and/or immunomodulators (ie, AZA, MTX, or 6-MP) at adequate therapeutic doses; OR ii) Has a history of failure to respond to, or tolerate, an adequate course of corticosteroids and/or immunomodulators (ie, AZA, MTX, or 6-MP); OR iii) Is corticosteroid dependent or has a history of corticosteroid dependency; AND b) Has not previously received an approved biologic for CD (ie, infliximab, adalimumab, certolizumab pegol, ustekinumab, natalizumab, vedolizumab or approved biosimilars of these agents) 6. Subjects on oral corticosteroids (eg, prednisone, budesonide) at a prednisone-equivalent dose of * 40 milligram (mg)/day or * 9 mg/day of budesonide are permitted provided doses meeting these requirements are stable for 3 weeks prior to baseline (Week 0) or these have been discontinued at least 3 weeks prior to baseline 7. Subjects on the immunomodulators AZA, 6-MP, or MTX at screening (or recently prior), must discontinue these medications at least 3 weeks prior to baseline 8. Has screening laboratory test results within the following parameters: a) Hemoglobin: * 8.5 gram per decilitre (g/dL) b) White blood cells (WBC): > 3.5 x 103/microlitre (µL) c) Neutrophils: >1.5 x 103/µL d) Platelets: > 100 x 103/µL e) Serum creatinine: < 1.7 milligram per decilitre (mg/dL) f) Aspartate transaminase (AST) and alanine transaminase (ALT) concentrations: Within 2 times the upper limit of normal range for the laboratory conducting the test g) Direct (conjugated) bilirubin: < 1.0 mg/dL 9. Is considered eligible per the following tuberculosis (TB) screening criteria: a) Has no history of latent or active TB prior to screening; exceptions are made for a subject who: * Is currently receiving treatment for latent TB without evidence of active TB (or has initiated treatment for latent TB prior to Week 0 study agent administration) * Has a history of latent TB and documentation of having completed adequate treatment for latent TB within 5 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous TB treatment and provide/obtain appropriate documentation. b) Has no signs or symptoms suggestive of active TB upon medical history and/or physical examination. c) Has had no recent, known close contact with a person with active T
Exclusion criteria
Exclusion criteria: A subject who meets any of the following criteria may not be enrolled in the study: 1. 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 2. 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. Subjects with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present 3. 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 4. At any time received any monoclonal antibody (including biosimilars) targeting tumor necrosis factor alfa (TNF*), IL-12, or IL-23, or anti-integrin agents approved for CD (ie, vedolizumab or natalizumab) or has received any of the following medications or therapies within the specified periods prior to baseline: a) Any other investigational agent for CD (eg other biologics, small molecules or anti-sense ribonucleic acid (RNA) such as mongersen), unless at least 3 months or 5 half-lives have elapsed since last dose b) Intravenous (IV) corticosteroids as a treatment for CD < 3 weeks prior to baseline c) Oral immunomodulatory agents other than AZA, 6-MP, or MTX (eg, Janus kinase [JAK] inhibitors, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, tofacitinib, or mycophenolate mofetil) < 4 weeks prior to baseline (Note that per inclusion criterion 7, typical immunomodulator agents [AZA, 6-MP or MTX] must have been discontinued at least 3 weeks prior to baseline.) d) Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral nutrition (TPN) as a treatment for CD < 3 weeks prior to baseline 5. 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 6. Has received a Bacillus Calmette*Guérin (BCG) vaccination within 12 months or any other live bacterial or live viral vaccination within 2 weeks of baseline 7. 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 8. Has current signs or symptoms of infection, or recent (within 8 weeks prior to baseline) history of herpes zoster or serious infection (including any requiring hospitalization) Established nonserious infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator 9. Has evidence of current active infection, including TB, or a nodule suspicious for lung malignancy on screening or any other available chest radiograph, unless
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective is to compare the efficacy of treatment with ustekinumab to that of adalimumab in biologic naïve subjects with moderately-to-severely active Crohn*s Disease (CD) who have previously failed or were intolerant to conventional therapy (corticosteroids and/or immunomodulators, ie, azathioprine, 6-mercaptopurine, or methotrexate), as measured by clinical remission at one year. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives are to evaluate the following in biologic naïve subjects with moderately-to-severely active CD treated with ustekinumab or adalimumab: - Other measures of clinical efficacy (eg, clinical response) including reductions in frequent concomitant medications associated with adverse outcomes (eg steroids, narcotics) - Anti-inflammatory efficacy assessed with biomarkers (eg, fecal calprotectin, C-reactive protein) - Endoscopic endpoints (eg, endoscopic remission) - Safety (eg, proportions of subjects with serious adverse events, all adverse events, etc.) - CD-related healthcare utilization (eg, CD-related hospitalizations, surgeries, emergency room [ER] visits) and the need to initiate another biologic treatment - Patient Reported Outcome (PRO) assessments such as Inflammatory Bowel Disease Questionnaire (IBDQ) and Patient Reported Outcome Measurement Information System (PROMIS), such as quality of life. | — |
Countries
Netherlands
Outcome results
None listed