A study of LY3471851 in adult participants with moderately to severely active ulcerative colitis (UC)

• Register: EUCTR
• Last refreshed on: 23 May 2022
• Main ID: EUCTR2020-003017-35-BE
• Date of registration: 05/02/2021
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A study of LY3471851 in adult participants with moderately to severely active ulcerative colitis (UC)
• Scientific title: An Adaptive Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of LY3471851 (NKTR-358) in Patients with Moderately to Severely Active Ulcerative Colitis - INSTRUCT-UC
• Date of first enrolment: 15/04/2021
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-003017-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Adaptive If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, China, Czech Republic, Czechia, France, Georgia, Germany, Hungary, India, Israel, Japan, Korea, Republic of, Latvia, Poland, Romania, Russian Federation, Slovakia, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly and Company

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

Inclusion criteria:
•Are male or female patients =18 and =80 years of age at the time of initial screening
•Have moderately to severely active ulcerative colitis (UC) as defined by a modified Mayo score (MMS) of 4 to 9 with an endoscopic subscore (ES) =2, with endoscopy performed within 14 days before baseline
•Have an established diagnosis of UC of =3 months in duration before baseline (Week 0)
•Have evidence of UC extending proximal to the rectum (with =15 centimeter (cm) of involved colon)
•Have up-to-date colorectal cancer surveillance performed according to local standard
•Participants are either one of the following:
-Have failed conventional treatments including inability to tolerate oral or intravenous corticosteroids or immunomodulators (6-mercaptopurine or azathioprine or methotrexate), or history of corticosteroid dependence and neither failed or demonstrated intolerance to advanced OR,
-Have failed or demonstrated intolerance to advanced therapies such as treatment with 1 or more advance therapies (eg, tumor necrosis factor [TNF} antagonists, anti-integrin therapies, anti- IL12/23p40 therapies, Janus kinase [JAK] inhibitor)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
•Have been diagnosed with indeterminant colitis, proctitis (colitis limited to the rectum only; less than 15 centimeter (cm) from the anal verge or Crohn’s disease
• Have had or will need abdominal surgery for UC (for example, subtotal colectomy)
•Have failed 3 or more classes of advanced therapies approved for treatment of UC (eg, tumor necrosis factor [TNF] antagonists, anti-integrin therapies, anti-IL12/23p40 therapies, Janus kinase [JAK] inhibitor)
•Have evidence of active tuberculosis (TB), or have a past history of active TB, regardless of treatment, or are diagnosed with latent tuberculosis infection (LTBI) at screening
•Have human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), or acute or chronic hepatitis B infection or current hepatitis C infection
•Have had recent clostridium difficile , cytomegalovirus or other intestinal infection
•Have had lymphoma, leukemia, or any malignancy within the past 10 years
•Are pregnant, breastfeeding, or planning pregnancy (women only), or within 20 weeks after receiving the last dose of study agent


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: LY3471851
Product Code: LY3471851
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LY3471851
Current Sponsor code: SUB210687
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.5-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To determine whether LY3471851 is superior to placebo in inducing clinical remission in participants with moderately to severely active Ulcerative Colitis (UC)

Primary end point(s): Difference in the proportion of participants who achieve clinical remission at Week 12

Secondary Objective: •To evaluate the efficacy of induction treatment with LY3471851 compared to placebo with respect to clinical, endoscopic, and histologic improvement
•To evaluate the efficacy of maintenance treatment with LY3471851 compared to placebo with respect to clinical, endoscopic,
and histologic improvement
•To evaluate the efficacy of treatment with LY3471851 compared to placebo with respect to patient-reported outcomes and quality of life measures
•To evaluate the PK of LY3471851

Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome(s)

Secondary end point(s): •Difference between LY3471851 and placebo in the proportion of participants who have not permanently discontinued at Week 12 and have achieved at Week 12: clinical response, endoscopic remission, endoscopic response, symptomatic remission, symptomatic response, histologic remission, histologic-endoscopic mucosal healing
•Difference between LY3471851 and placebo in the proportion of participants who were responders at Week 12 (Week 12 Responders) and have not permanently discontinued at Week 52, who at Week 52 still have: clinical remission, clinical response, endoscopic remission, endoscopic response, symptomatic remission, symptomatic response, histologic remission, histologic-endoscopic mucosal healing
•Comparison of mean changes from baseline to Week 12 and to Week 52 in scores for: IBDQ, Urgency NRS, Abdominal Pain NRS, Nocturnal Stools, Bristol Stool Scale, PGR-S, Fatigue NRS
•Week 12 LY3471851 trough concentrations

Timepoint(s) of evaluation of this end point: Week 12, Week 12 to 52 and Week 52

Secondary ID(s)

2020-003017-35-SK

J1P-MC-KFAH

Source(s) of Monetary Support

Eli Lilly and Company

Ethics review

Status: Approved
Approval date: 15/04/2021
Contact: