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

Phase 3

Completed

• Conditions: chronic inflammation of the intestinal wall; enteritis regionalis; 10017969

• Registration Number: NL-OMON50125
• Lead Sponsor: Janssen-Cilag

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 12

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective is to compare the efficacy of treatment with ustekinumab<br /><br>to that of adalimumab in biologic naïve subjects with moderately-to-severely<br /><br>active Crohn*s Disease (CD) who have previously failed or were intolerant to<br /><br>conventional therapy (corticosteroids and/or immunomodulators, ie,<br /><br>azathioprine, 6-mercaptopurine, or methotrexate), as measured by clinical<br /><br>remission at one year.</p><br>