A Phase 3, Randomized, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Guselkumab in Participants with Fistulizing, Perianal Crohn*s Disease

Phase 3

• Conditions: inflammatory bowel disease (IBD); Crohn; 10017969

• Registration Number: NL-OMON53768
• Lead Sponsor: Janssen-Cilag

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 11

Inclusion Criteria

1. Aged 18 years (or the legal age of consent in the jurisdiction in which the
study is taking
place) or over.
2. Must have a diagnosis of Crohn*s disease with a minimum duration of at least
3 months
(confirmed by clinical evaluation and a combination of endoscopic, histological,
radiological, and/or biochemical investigations).
3. Has at least one active draining perianal fistula as a complication of
Crohn*s disease,
confirmed by screening MRI results.
4.2 Is naïve to biologics, or has previously demonstrated lack of initial
response (ie, primary
non-responders), responded initially but then lost response with continued
therapy (ie,
secondary non-responders), or were intolerant to a maximum of 2 classes of
biologic
agents at a dose approved for the treatment of Crohn's disease (ie, infliximab,
adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars for these
agents). Please refer to Appendix 4 for details.
OR
History of failure to respond to, or tolerate, at least 1 of the following
therapies for the
treatment of Crohn's disease: oral corticosteroids (including budesonide and
beclomethasone dipropionate) or immunomodulators (AZA, 6-MP, MTX).
Participants with prior exposure to IL-12/23 or IL-23 agents are ineligible for
entry into
this protocol, with the exception of participants who have had exposure to
ustekinumab
at its approved labeled dosage AND have met the required 16 week washout
criterion
AND have not demonstrated failure or intolerance to ustekinumab. Please refer to
Appendix 5 for details.
5.1 Had a history of failure to respond to, or tolerate, at least 1 of the
following therapies
for fistula treatment: antibiotics (ie, ciprofloxacin, metronidazole) and/or
immunomodulators (AZA, 6-MP, MTX).Please refer to Appendix 3 for details.
Note: Participants refractory, intolerant or dependent on corticosteroids will
be
permitted to participate in the study.
6. Adhere to the following requirements for concomitant medication for the
treatment of
Crohn's disease. The following medications are permitted if doses meeting the
requirements listed below are stable or have been discontinued prior to
baseline and
within the timeframes specified below:
• Oral corticosteroids at a prednisone-equivalent dose at or below 20 mg/day, or
6 mg/day of budesonide, or 5 mg/day beclomethasone dipropionate, and on stable
dosing for at least 2 weeks or if recently discontinued, must have been stopped
for
at least 2 weeks.
• Conventional immunomodulators (ie, AZA, 6-MP, or MTX) for at least 12 weeks
and have been on a stable dose for at least 4 weeks or if recently
discontinued, must
have been stopped for at least 4 weeks.
• If receiving antibiotics as a primary treatment of luminal Crohn's disease,
all
antibiotics must be stopped prior to baseline.
7. If receiving enteral nutrition as a primary treatment for Crohn*s disease,
must have been
receiving for at least 2 weeks or if recently discontinued, must have been
stopped for at
least 2 weeks.
8. Screening laboratory test results within the following parameters, and if 1
or more of
the laboratory parameters is out of range, a single retest of laboratory values
is permitted
during the approximate 6-week screening period:
• Hemoglobin >=8.0 g/dL.
• White blood cells (WBCs)

Exclusion Criteria

1. Has a very severe luminal disease activity (defined as CDAI >=350).
2. Has any of the following:
• history of or concurrent rectovaginal fistulas, rectal and/or anal stenosis
(unless the
participant undergoes surgical dilation prior to baseline), diverting stomas
with
anastomotic leakage, abscess or collections which are not properly drained.
• colonic mucosal dysplasia or pre-cancerous lesions that have not been removed,
demyelinating disease, or systemic lupus erythematosus.
3. Has current complications of Crohn*s disease, such as symptomatic strictures
or
stenoses, short gut syndrome, or any other manifestation, that might be
anticipated to
require surgery, could preclude any fistula evaluation (both clinical and
radiological) to
assess response to therapy, or would possibly confound the ability to assess
the effect
of treatment with guselkumab.
4. Has a stool culture or other examination positive for an enteric pathogen,
including
Clostridioides difficile (formerly known as Clostridium difficile) toxin, in
the previous
4 months, unless a repeat examination is negative and there are no signs of
ongoing
infection with that pathogen.
5. Has a history of, or ongoing, chronic or recurrent infectious disease,
including but not
limited to, chronic renal infection, chronic chest infection (eg,
bronchiectasis), recurrent
urinary tract infection (eg, recurrent pyelonephritis or chronic non-remitting
cystitis),
or open, draining, or infected skin wounds or ulcers.
6. Has a history of serious infection (eg, hepatitis, sepsis, pneumonia, or
pyelonephritis),
including any infection requiring hospitalization, during the 8 weeks before
baseline.
7. Currently has a malignancy or has a history of malignancy within 5 years
before
screening (with the exception of a nonmelanoma skin cancer that has been
adequately
treated with no evidence of recurrence for at least 3 months [defined as a
minimum of
12 weeks] before the first study intervention administration or cervical
carcinoma in
situ that has been treated with no evidence of recurrence for at least 3 months
before
the first study intervention administration).
8. Has a known history of lymphoproliferative disease, including lymphoma, or
signs and
symptoms suggestive of possible lymphoproliferative disease, such as
lymphadenopathy, hepatomegaly, or splenomegaly, or monoclonal gammopathy of
undetermined significance.
9. Has a history of severe, progressive, or uncontrolled renal, genitourinary,
hepatic,
hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic,
psychiatric, or metabolic disturbances, or signs and symptoms thereof.
10. Has a transplanted organ (with exception of a corneal transplant >12 weeks
before
screening).
11. Is unable or unwilling to undergo multiple venipunctures because of poor
tolerability
or lack of adequate venous access.
12. Is unwilling to get a subcutaneous injection.
13. Has unstable suicidal ideation or suicidal behavior in the last 6 months
that may be
defined as a Columbia-Suicide Severity Rating Scale (C-SSRS) rating at
screening of:
Suicidal Ideation with Intention to Act (*Ideation level 4*), Suicidal Ideation
with
Specific Plan and Intent (*Ideation level 5*), or suicidal behavior (actual
suicide
atte

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of this study is the proportion of participants who<br /><br>achieve combined fistula remission at Week 2.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>-proportion of participants who achieve combined fistula remission at week 48<br /><br>-proportion of participants who achieve clinically assessed fistula remission<br /><br>at week 24<br /><br>-proportion of participants who achieve radiological fistula remission based on<br /><br>radiological findings assessed by MRI at week 24<br /><br>-proportion of participants who achieve clinically assessed fistula response at<br /><br>week 24<br /><br>-proportion of participants who achieve clinically assessed fistula response at<br /><br>week 12</p><br>