Overview

Safety and Efficacy of Efavaleukin Alfa in Participants With Moderately to Severely Active Ulcerative Colitis

Status:
Not yet recruiting
Trial end date:
2024-06-24
Target enrollment:
0
Participant gender:
All
Summary
The main purpose of this study is to evaluate the effect of efavaleukin alfa on induction of clinical remission in participants with moderately to severely active ulcerative colitis (UC). Participants will be randomized to receive 1 of 3 efavaleukin alfa doses or placebo during a 12-week induction period. Participants who complete the 12-week induction period will have the option to enter an exploratory long-term treatment period for up to 40 weeks (total of up to 52 weeks of treatment) if, in the opinion of the investigator, they may benefit from continued treatment. During the long-term period, participants randomized to efavaleukin alfa will remain on the same efavaleukin alfa blinded dose; participants randomized to placebo who achieved clinical response at week 12 will remain on placebo; and placebo non-responders (ie, participants randomized to placebo who did not achieve clinical response at week 12) will receive efavaleukin alfa in a blinded manner during continued treatment. All participants will complete a safety follow-up visit 6 weeks after their last dose of investigational product.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Amgen
Criteria
Key Inclusion Criteria:

- Participant has provided informed consent prior to initiation of any study specific
activities or procedures. In Japan, if a participant is younger than 20 years at the
time of signing the informed consent, the informed consent must be obtained from both
the participant and their legal representative.

- Men and women aged ≥ 18 to < 80 years at screening visit (≥ 19 to < 80 in South
Korea).

- Diagnosis of UC established ≥ 3 months prior to enrollment by clinical and endoscopic
evidence and corroborated by a histopathology report. If a histopathology report is
not available at screening, then additional biopsies may be taken during the screening
period for local histopathology analysis to corroborate.

- Moderately to severely active UC as defined by a modified Mayo score of 5 to 9, with a
centrally read rectosigmoidoscopy endoscopic subscore ≥ 2 and no subscore < 1 prior to
day 1.

- Has documentation of:

- A surveillance colonoscopy (performed according to local standard) within 12
months of day 1 visit for participants with pancolitis of > 8 years duration, or
participants with left-sided colitis of > 12 years duration, or participants with
primary sclerosing cholangitis.

- For all other participants, up-to-date colorectal cancer surveillance (performed
according to local standard). Participants 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, at the
discretion of the investigator.

- Participants must have demonstrated inadequate response, loss of response, or
intolerance to at least 1 conventional therapy, biologic therapy, or targeted small
molecule therapy (ie, Janus kinase [JAK]-inhibitor), as follows:

1. Conventional therapy failed participants:

- 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).

- 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).

- 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 (eg, ≥ 1.5 mg/kg/day) or 6-mercaptopurine
(eg, ≥ 0.75 mg/kg/day), 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.

- 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-tumor necrosis
factor [TNF] antibody, anti-integrin antibody, or interleukin [IL]-12/23
antagonists) that is indicated for the treatment of UC.

2. Biologic or targeted small molecule therapy failed participants: 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). The therapy used to
qualify the participant for entry into this category must be approved for the
treatment of UC in the country of use, at the time of use. Participants must
fulfil one of the following criteria:

- Inadequate response: signs and symptoms of persistently active disease
despite induction treatment at the approved induction dosing that was
indicated in the product label at the time of use.

- Loss of response: recurrence of signs and symptoms of active disease during
approved maintenance dosing following prior clinical benefit
(discontinuation despite clinical benefit does not quality as having failed
or being intolerant to UC biological therapy or JAK inhibitor).

- Intolerance: history of intolerance to infliximab, adalimumab, golimumab,
vedolizumab, ustekinumab, tofacitinib or other approved biologicals or JAK
inhibitors (including but not limited to infusion-related event,
demyelination, congestive heart failure, or any other drug-related adverse
event that led to a reduction in dose or discontinuation of the medication).

- If receiving any of the following therapies, participants must have stable dosage for
the specified duration:

- 5-aminosalicylates (ASAs), stable dosage for ≥ 2 weeks prior to screening
endoscopy.

- Oral corticosteroids: prednisone ≤ 20 mg/day or its equivalent, stable dose for ≥
2 weeks prior to screening endoscopy.

- Budesonide: extended release tablets 9 mg/day [budensonide MMX], stable dose for
≥ 2 weeks prior to screening endoscopy.

- Conventional immunomodulators: azathioprine, 6-mercaptopurine, methotrexate,
stable dosage for ≥ 12 weeks prior to screening endoscopy.

Key Exclusion Criteria:

- Diagnosis of Crohn's disease, inflammatory bowel disease unclassified (indeterminate
colitis), microscopic colitis, ischemic colitis, or clinical findings suggestive of
Crohn's disease.

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

- Participant has had extensive surgery for UC (for example, subtotal colectomy), or is
likely to require surgery for the treatment of UC during the study.

- Currently receiving or had treatment within 12 months prior to screening with T cell
depleting agents (eg, antithymocyte globulin, Campath).

- Participant has received any of the following prescribed medication or therapy within
the specified time period:

- Anti TNF antibodies (eg, infliximab, adalimumab, golimumab) < 8 weeks prior to
screening rectosigmoidoscopy.

- Anti integrin antibodies (eg, vedolizumab) < 8 weeks prior to screening
rectosigmoidoscopy.

- IL 12/23 antagonist (eg, ustekinumab) < 8 weeks prior to screening
rectosigmoidoscopy.

- JAK inhibitors (eg, tofacitinib) < 4 weeks prior to screening rectosigmoidoscopy.

- Any other commercially approved biologic agent or targeted small molecule < 8
weeks prior to screening rectosigmoidoscopy or < 5 half lives prior to screening
rectosigmoidoscopy, whichever is longer

- Immunomodulatory medications, including oral cyclosporine, intravenous
cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, thalidomide < 4 weeks
prior to screening rectosigmoidoscopy.

- Any investigational biologic therapy within 8 weeks prior to screening
rectosigmoidoscopy or < 5 half-lives prior to screening rectosigmoidoscopy,
whichever is longer.

- Has used apheresis (eg, Adacolumnâ apheresis) < 2 weeks prior to screening
rectosigmoidoscopy.