|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Moderate to Severe Active Ulcerative Colitis
|Medical condition in easily understood language
|Body processes [G] - Immune system processes [G12]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10017947 - Gastrointestinal disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To evaluate the effect of efavaleukin alfa on induction of clinical remission
|Secondary objectives of the trial
|- To evaluate the effect of efavaleukin alfa on induction of clinical
- To evaluate the effect of efavaleukin alfa on induction of endoscopic
- To evaluate the effect of efavaleukin alfa on induction of symptomatic
- To evaluate the effect of efavaleukin alfa as induction therapy on
combined endoscopic and histologic remission
- To evaluate the effect of efavaleukin alfa as induction therapy on
change in histological score
- To evaluate the safety and tolerability of efavaleukin alfa
|Trial contains a sub-study
|Principal inclusion criteria
|101 Subject has provided informed consent prior to initiation of study.
102 Age ≥18 years to <80 years at screening visit, except in South Korea where age ≥19 years to <80 years at screening visit.
103 Diagnosis of UC established ≥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 >8 years duration, or subjects with left-sided colitis of >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:
- 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 corticosteroiddependent 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
- 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
- History of intolerance to at least 1 immunomodulator 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
- 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 or S1P modulator)
- Intolerance: history of intolerance to infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib or other approved biologicals or JAK inhibitors or S1P modulators (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)
107 If receiving any of the following therapies, subjects must have stable dosage for the specified duration:
- 5-aminosalicylates (ASAs), stable dosage for ≥ 2 weeks prior to screening endoscopy
- Oral corticosteroids: prednisone up to 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 at least 2 weeks prior to screening endoscopy
- Beclomethasone dipropionate: gastro-resistant prolonged-release tablet 5 mg/day, stable dose for ≥ 2 weeks prior to screening endoscopy
- Conventional immunomodulators: azathioprine, 6-mercaptopurine, methotrexate, stable dosage for at least 8 weeks prior to screening endoscopy
|Principal exclusion criteria
|201 Diagnosis of Crohn’s disease, inflammatory bowel disease-unclassified, 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:
Any history or current evidence of high-grade dysplasia.
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.
Any history or current evidence of a nonadenoma-like
dysplasia-associated lesions or masses, with or without evidence of
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 as 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 enroll if they meet ALL the following criteria at screening:
No symptoms per tuberculosis worksheet provided by Amgen
documented history of adequate TB treatment or prophylactic treatment for latent TB
No known exposure to a case of active tuberculosis after most recent
Chest X-ray with no new radiographic findings suggestive of active TB
211 Any history of malignancy
212 Presence of 1 or more significant concurrent medical conditions per the investigator judgement
213 Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody or hepatitis B surface antibody in the presence of detectable viral DNA in peripheral blood, assessed by polymerase chain reaction. Subjects positive for HBcAb and/or HBsAb without history of prior vaccination and without detectable serum hepatitis B viral DNA by PCR are allowed to enroll, provided the subject undergoes monitoring of serum hepatitis B viral DNA by PCR at every 2 months during the treatment period and up to 6 weeks after the end of treatment for the study. Subjects with a history of hepatitis B vaccination without history of hepatitis B infection are allowed to enroll.
214 Positive for hepatitis C antibody in the presence of detectable viral RNA in peripheral blood, assessed by PCR. Subjects positive for HCAb without detectable viral RNA by PCR are allowed to enroll.
215 Known history of Human Immunodeficiency Virus (HIV) or positive HIV test at screening.
216 Inherited immunodeficiency syndrome.
217 Required systemic corticosteroid use for any indication other than UC.
218 Have had a bone marrow or solid organ transplantation.
219 Have had extra-abdominal surgery without full recovery prior to screening.
|E.5 End points
|Primary end point(s)
|Clinical remission at week 12
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|Clinical response at week 12
Endoscopic remission at week 12
Symptomatic remission at week 12
Combined endoscopic remission and histologic remission of the colon
tissue at week 12
Change from baseline in histological score at week 12 as measured by
Treatment-emergent adverse events
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|End of long-term treatment (Long-term extension is additional 40 week +6 week follow-up)
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days