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

  • STATUS
    Recruiting
  • End date
    Aug 26, 2024
  • participants needed
    320
  • sponsor
    Amgen
Updated on 12 October 2022
cancer
corticosteroids
remission
methotrexate
endoscopy
prednisone
adalimumab
infliximab
tumor necrosis factor
mercaptopurine
budesonide
vedolizumab
azathioprine
golimumab
tumour necrosis
immunomodulators
thiopurines
janus kinase inhibitor
pancolitis
aminosalicylates

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.

Details
Condition Ulcerative Colitis
Treatment Placebo, Efavaleukin Alfa
Clinical Study IdentifierNCT04987307
SponsorAmgen
Last Modified on12 October 2022

Eligibility

Yes No Not Sure

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
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
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
-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

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note