A Phase 2, Dose-finding, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Efavaleukin Alfa Induction Therapy in Subjects with Moderately to Severely Active Ulcerative Colitis

Phase 2

Recruiting

• Conditions: Colitis gravis; Inflammatory bowel disease; 10017969

• Registration Number: NL-OMON54105
• Lead Sponsor: Amgen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 7

Inclusion Criteria

101 Subject has provided informed consent prior to initiation of study, 102
Aged from 18 years to 80 years at screening visit, 103 Diagnosis of UC
established at least 3 months prior to enrollment by clinical and endoscopic
evidence and corroborated by a histopathology report. 104 Moderately to
severely active UC as defined by a modified Mayo score of 5 to 9, with a
centrally read endoscopy subscore >= 2, 105 Has documentation of • a
surveillance colonoscopy within 12 months of day 1 visit for subjects with
pancolitis of at least 8 years duration, or subjects with left-sided colitis of
over 12 years duration, or subjects with primary sclerosing cholangitis. • For
all other subjects, up-to-date colorectal cancer surveillance. At the
discretion of the investigator a colonoscopy may be performed as the screening
endoscopy for this study. Subjects who do not have a colonoscopy report
available in source documentation will have a colonoscopy instead of
rectosigmoidoscopy performed as the screening endoscopy for the study. 106
Subjects must have demonstrated inadequate response, loss of response, or
intolerance to at least 1 conventional therapy, biologic therapy, or targeted
small molecule therapy (ie, JAK-inhibitor). 1) Conventional therapy failed
subjects: o Corticosteroids (corticosteroid-refractory colitis, defined as
signs and/or symptoms of active UC despite oral prednisone (or equivalent) at
doses of at least 30 mg/day for a minimum of 2 weeks; or
corticosteroid-dependent colitis, defined as: an inability to reduce
corticosteroids below the equivalent of prednisone 10 mg/day within 3 months of
starting corticosteroids without a return of signs and/or symptoms of active
UC; or a relapse within 3 months of completing a course of corticosteroids o
History of intolerance of corticosteroids (including, but not limited to,
Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, or neuropsychiatric
side-effects, including insomnia, associated with corticosteroid treatment) o
Immunomodulators: signs and/or symptoms of persistently active disease despite
at least 3 months treatment with one of the following at locally approved
doses: oral azathioprine or 6-mercaptopurine, or oral azathioprine or
6-mercatopurine within a therapeutic range as judged by thioguanine metabolite
testing, or a combination of a thiopurine and allopurinol within a therapeutic
range as judged by thioguanine metabolite testing o History of intolerance to
at least 1 immunomodulator (including but not limited to nausea/vomiting,
abdominal pain, pancreatitis, liver function test abnormalities, and
lymphopenia) and have neither failed nor demonstrated an intolerance to a
biological medication (anti-TNF antibody, anti-integrin antibody, or IL-12/23
antagonists) that is indicated for the treatment of UC. 2) Biologic or targeted
small molecule therapy failed subjects: those who demonstrated inadequate
response or loss of response or intolerance to biologic therapy for UC (eg,
anti-TNF antibodies or IL-12/23 antagonists, anti-integrin antibodies) or
targeted small molecules (eg, JAK inhibitors or S1P modulators). The therapy
used to qualify the subject for entry into this category must be approved for
the treatment of UC in the country of use, at the time of use. Subjects must
fulfil one of the foll

Exclusion Criteria

201 Diagnosis of Crohn's disease, inflammatory bowel diseaseunclassified,
microscopic colitis, ischemic colitis, or clinical findings suggestive of
Crohn's disease.

202 Disease limited to the rectum.

203 Evidence of toxic megacolon, fulminant colitis, intra-abdominal abscess, or
stricture/stenosis within the small bowel or colon.

204 Previous bowel resection or intestinal or intra-abdominal surgery.
• Have had extensive surgery for UC, or are likely to require surgery for the
treatment of UC during the study. Subjects who have had limited surgery for UC
may be allowed in the study, if this does not affect the assessment of
efficacy. Discussion with the sponsor must occur prior to screening of such
subjects.
• Have had any small bowel or colonic surgery within 6 months of day 1.
• Have had any nonintestinal intra-abdominal surgery within 3 months of day 1.

205 Adenoma and dysplasia exclusion criteria:
• Any current sporadic adenoma without dysplasia that has not been removed.
Once completely removed, the subject is eligible for study.
• Dysplasia occurring in flat mucosa, sporadic adenomas containing dysplasia,
and dysplasia-associated lesions or masses will be managed as follows:
o Any history or current evidence of high-grade dysplasia.
o Any history or current evidence of dysplasia occurring in flat
mucosa. This includes histopathology reporting indefinite for dysplasia,
low-grade dysplasia, and high-grade dysplasia.
o Any history or current evidence of a nonadenoma-like
dysplasia-associated lesions or masses, with or without evidence of dysplasia.
o Any current sporadic adenoma containing dysplasia or any current
adenoma-like dysplasia-associated lesions or masses that has not been removed.
Once completely removed, the patient is eligible for the study.

206 Stool positive for Clostridium difficile toxin at screening and other
enteric pathogens including but not limited to ova, parasites, Campylobacter,
salmonella, shigella, E coli 0157:H7, and Yersinia enterocolitica.

207 History or evidence of suicidal ideation (severity of 4 or 5) or any
suicidal behavior based on an assessment with the Columbia Suicide Severity
Rating Scale (C-SSRS) at screening

208 Active infection for which anti-infectives were indicated within 2 weeks
prior to screening visit OR presence of serious infection, defined s requiring
hospitalization or intravenous (IV) anti-infectives within 8 weeks prior to
screening visit.

209 Active tuberculosis or latent tuberculosis with no documented past history
of adequate treatment per local standard of care.

210 Positive test for TB during screening defined as: either a positive or
indeterminate QuantiFERON-TB or T-spot test OR positive purified protein
derivative.
• Subjects with a positive PPD and a history of Bacillus Calmette-Guerin
vaccination are allowed to enroll with a negative QuantiFERON®-TB or T-Spot
test and negative chest X-ray.
• Indeterminate QuantiFERON®-TB or T-spot test can be repeated once, based on
investigator judgment. Subjects can enroll if second result is negative.
Subjects with persistent indeterminate or positive test results must proceed as
below.

• Subjects with a positive PPD test or a positive or indeterminate QuantiFERON®-
TB or T-Spot test are allowed to enrol

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Clinical remission at week 12</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Clinical response at week 12<br /><br>• Endoscopic remission at week 12<br /><br>• Symptomatic remission at week 12<br /><br>• Combined endoscopic remission and histologic remission of the colon tissue at<br /><br>week 12<br /><br>• Change from baseline in histological score at week 12 as measured by Geboes<br /><br>score<br /><br>• Treatment-emergent adverse events</p><br>