Protocol 20170104: Randomized, double-blind, placebo-controlled, multicenter phase 2 dose-finding study to assess the safety and efficacy of an induction therapy with Efavaleukin alfa in participants with moderately to severely active ulcerative colitis

Argentina, Austria, Belgium, Bulgaria, Canada, Czech Republic, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Latvia, Mexico, Netherlands, Poland, Romania, Russian Federation, Slovakia, Spain, Switzerland, Taiwan, Turkey, Ukraine, United States (ICTRP)

ICTRP Studien-ID
EUCTR2021-002537-41 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
Randomisierte, doppelblinde, placebokontrollierte, multizentrische Dosisfindungsstudie der Phase 2 zur Beurteilung der Sicherheit und Wirksamkeit einer Induktionstherapie mit Efavaleukin alfa bei Teilnehmenden mit mässig bis stark aktiver Colitis ulcerosa (BASEC)

Wissenschaftlicher Titel
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 (ICTRP)

Öffentlicher Titel
Safety and Efficacy of Efavaleukin Alfa in Subjects with Moderately to Severely Active Ulcerative Colitis (ICTRP)

Untersuchte Krankheit(en)
Moderate to Severe Active Ulcerative Colitis
MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856;Therapeutic area: Body processes [G] - Immune system processes [G12] (ICTRP)

Untersuchte Intervention

Product Name: Efavaleukin Alfa
Product Code: AMG 592
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EFAVALEUKIN ALFA
Current Sponsor code: AMG 592
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

(ICTRP)

Studientyp
Interventional clinical trial of medicinal product (ICTRP)

Studiendesign
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4 (ICTRP)

Ein-/Ausschlusskriterien
Gender:
Female: yes
Male: yes

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; and in Taiwan where age =20 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 and no subscore <1 prior to day 1. Subjects require qualifying Mayo daily symptom diary subscores (a stool frequency subscore =1 and rectal bleeding subscore =1) to proceed to bowel preparation for screening endoscopy.

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 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
- 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 following criteria:
- Inadequate response: signs and symptoms of persistently active disease despite induction treatment at the approved induction dosing t (ICTRP)

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 dysplasia.
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 4 weeks prior to screening visit OR presence of serious infection, defined as requiring hospitalization or intravenous 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 tubercul

Primäre und sekundäre Endpunkte
Main Objective: To evaluate the effect of efavaleukin alfa on induction of clinical remission;Secondary Objective: - To evaluate the effect of efavaleukin alfa on induction of clinical response
- To evaluate the effect of efavaleukin alfa on induction of endoscopic remission
- To evaluate the effect of efavaleukin alfa on induction of symptomatic remission
- 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;Primary end point(s): Clinical remission at week 12
;Timepoint(s) of evaluation of this end point: Week 12 (ICTRP)

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 Geboes score
Treatment-emergent adverse events
;Timepoint(s) of evaluation of this end point: Week 12 (ICTRP)

Registrierungsdatum
29.12.2022 (ICTRP)

Einschluss des ersten Teilnehmers
18.03.2023 (ICTRP)

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Medical Information, medinfo.baltics@amgen.com, +3705219 7461, Amgen Switzerland AG Vilnius branch (ICTRP)

Sekundäre IDs
20170104, 2021-002537-41-CZ (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-002537-41 (ICTRP)