An Efficacy and Safety Study of LYC-30937-EC in Subjects With Active Ulcerative Colitis

Colitis, Ulcerative Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Assess the Efficacy and Safety of Induction Therapy With LYC-30937-EC in Subjects With Active Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02762500
• Other study ID #: LYC-30937-2001
• Secondary ID: 2016-000518-31
• Status: Completed
• Phase: Phase 2
• Start date: July 2016
• Est. completion date: May 2018

Study information

• Verified date: March 2019
• Source: Lycera Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the efficacy and safety of LYC-30937-EC given orally once daily in subjects with active ulcerative colitis (UC) defined as a total Mayo score (TMS) of 4-11 inclusive, with an endoscopic score of ≥ 2 and a rectal bleeding score of ≥ 1 at screening.

Description:

Approximately 120 subjects will be randomized to receive either enteric-coated (EC) LYC-30937-EC 25 mg PO once daily (QD) or matching placebo PO QD for the duration of 8 weeks. Randomization will be stratified based on previous exposure to anti-tumor necrosis factor (TNF) agents such that at least 50% of the randomized subjects will be anti-TNF naïve .

The study will consist of 3 phases:

• screening phase: up to 4 weeks

• double-blind placebo-controlled phase treatment: 8 weeks

• post-treatment follow-up: 2 weeks

Eligible subjects will be randomized at Week 0 (Study Day 1) to either LYC-30937-EC 25 mg or placebo. Screening will occur from Study Days -28 to -1. Randomization and first dosing will occur at Week 0/Study Day 1. Double-blind study visits will occur at Weeks 2, 4, and 8, with the last dose at Week 8/Study Day 57. Subjects will return at Week 10 for a post-treatment safety follow-up visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: May 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Clinical UC diagnosis = 6 months prior to screening with minimum disease extent of = 15cm from anal verge.

• Active UC defined as a TMS of 4-11 (inclusive) with endoscopic subscore of = 2 and rectal bleeding subscore of = 1 at screening.

• Females of childbearing potential must have a negative pregnancy test at screening and baseline visits and must agree to use acceptable methods of birth control while in the trial and for 30 days after taking the last dose of study drug.

• May be currently receiving treatment with oral aminosalicylates (ASA) for = 6 weeks at a stable dose for = 3 weeks prior to the screening screening endoscopy and/or thiopurine at a stable dose = 8 weeks prior to the screening endoscopy and/or prednisone (dose 20 mg daily) or equivalent for = 4 weeks and receiving stable dose for = 2 weeks prior to screening endoscopy

• able to provide written informed consent and be compliant with study procedures.

Exclusion Criteria:

• History of Crohn's disease (CD) or indeterminate colitis or the presence or history of fistula consistent with CD.

• Presence of colon polyps.

• Severe extensive disease that in the investigators discretion is likely to require colonic surgery during the 8 week double-blind portion of the trial (eg, fulminant colitis, toxic megacolon, bowel perforation, evidence of acute abdomen).

• History of alcohol or drug abuse within 1 year of randomization.

• History of cancer including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been adequately treated with no recurrence for = 1 year prior to screening.

• History or currently active primary or secondary immunodeficiency.

• Clinically relevant hepatic, neurologic, pulmonary, ophthalmological, gastrointestinal, endocrine, psychiatric, or other major systemic disease making implementation of the study difficult or that would put the subject at risk by participating in the study

• Positive test for Clostridium difficile or positive stool culture for enteric pathogens or presence of ova or parasites at screening.

• Liver function tests > 1.5 x upper limit of normal (ULN) or direct bilirubin > 1.5 x ULN

• Hemoglobin < 8.5 g/dl

• Neutrophils < 1500/mm3

• White blood cell (WBC) count < 3000/mm3

• Platelets < 80000 mm3

• International normalized ratio (INR) > 1.5

• Treatment with an immunosuppressant agent within 8 weeks of screening.

• Previous exposure to = 2 approved or investigational biologic agents to treat UC.

• History of UC treatment with a biologic agent within 12 weeks of screening.

• Treatment with rectal steroids within 2 weeks of screening.

• Treatment with an investigational agent within 30 days of screening.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• LYC-30937-EC

• Placebo

Locations

Country	Name	City	State
Canada	Lycera Investigational Site	Toronto	Ontario
Canada	Lycera Investigational Site	Victoria	British Columbia
Czechia	Lycera Investigational Site	Ostrava
Czechia	Lycera Investigational Site	Praha
Czechia	Lycera Investigational Site	Praha 3
Czechia	Lycera Investigational Site	Slany
Czechia	Lycera Investigational Site	Usti nad Labem
Hungary	Lycera Investigational Site	Budapest
Hungary	Lycera Investigational Site	Budapest
Hungary	Lycera Investigational Site	Debrecen
Hungary	Lycera Investigational Site	Debrecen
Hungary	Lycera Investigational Site	Hatvan
Netherlands	Lycera Investigational Site	Amsterdam
Netherlands	Lycera Investigational Site	Rotterdam
Poland	Lycera Investigational Site	Bydgoszcz
Poland	Lycera Investigational Site	Bydgoszcz
Poland	Lycera Investigational Site	Katowice
Poland	Lycera Investigational Site	Katowice
Poland	Lycera Investigational Site	Katowice
Poland	Lycera Investigational Site	Kielce
Poland	Lycera Investigational Site	Krakow
Poland	Lycera Investigational Site	Krakow
Poland	Lycera Investigational Site	Ksawerów
Poland	Lycera Investigational Site	Lódz
Poland	Lycera Investigational Site	Lublin
Poland	Lycera Investigational Site	Lublin
Poland	Lycera Investigational Site	Nowa Sól
Poland	Lycera Investigational Site	Piaseczno
Poland	Lycera Investigational Site	Poznan
Poland	Lycera Investigational Site	Skierniewice
Poland	Lycera Investigational Site	Sopot
Poland	Lycera Investigational Site	Staszów
Poland	Lycera Investigational Site	Szczecin
Poland	Lycera Investigational Site	Warszawa
Poland	Lycera Investigational Site	Warszawa
Poland	Lycera Investigational Site	Wloclawek
Poland	Lycera Investigational Site	Wroclaw
Poland	Lycera Investigational Site	Wroclaw
Poland	Lycera Investigational Site	Wroclaw
Poland	Lycera Investigational Site	Wroclaw
Serbia	Lycera Investigational Site	Belgrade
Serbia	Lycera Investigational Site	Belgrade
Serbia	Lycera Investigational Site	Kragujevac
Serbia	Lycera Investigational Site	Niš
Serbia	Lycera Investigational Site	Subotica
Serbia	Lycera Investigational Site	Zrenjanin
United States	Lycera Investigational Site	Ann Arbor	Michigan
United States	Lycera Investigational Site	Baton Rouge	Louisiana
United States	Lycera Investigational Site	Bronx	New York
United States	Lycera Investigational Site	Brooklyn	New York
United States	Lycera Investigational Site	Chicago	Illinois
United States	Lycera Investigational Site	Decatur	Georgia
United States	Lycera Investigational Site	Flourtown	Pennsylvania
United States	Lycera Investigational Site	Greenville	North Carolina
United States	Lycera Investigational Site	Hollywood	Florida
United States	Lycera Investigational Site	Houston	Texas
United States	Lycera Investigational Site	Houston	Texas
United States	Lycera Investigational Site.	Houston	Texas
United States	Lycera Investigational Sites	Houston	Texas
United States	Lycera Investigational Site	Little Rock	Arkansas
United States	Lycera Investigational Site	Long Beach	California
United States	Lycera Investigational Site	Louisville	Kentucky
United States	Lycera Investigational Site	Marietta	Georgia
United States	Lycera Investigational Site	Miami	Florida
United States	Lycera Investigational Site	Mission Hills	California
United States	Lycera Investigational Site	Nashville	Tennessee
United States	Lycera Investigational Site	New York	New York
United States	Lycera Investigational Site	Philadelphia	Pennsylvania
United States	Lycera Investigational Site	Rialto	California
United States	Lycera Investigational Site	San Antonio	Texas
United States	Lycera Investigational Site	Sayre	Pennsylvania
United States	Lycera Investigational Site	Union City	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Lycera Corp.

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Hungary,  Netherlands,  Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Subjects With Type of Adverse Events (AEs) Serious Adverse Events (SAEs) and AEs That Led to Discontinuation of Treatment.	Adverse events (AEs) were collected from the time a subject signed the informed consent. Treatment-emergent adverse events (TEAEs) are AEs occurring or worsening after the first dose of study drug (LYC-30937-EC 25 mg or placebo). Adverse event severity was assessed by the Investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.03, with grading as follows: Grade 1 = mild (asymptomatic or mild symptoms), Grade 2 = moderate (minimal, local intervention, or noninvasive intervention indicated); Grade 3 = severe (or medically significant but not life-threatening); Grade 4 = life-threatening; Grade 5 = death.	10 weeks
Primary	Number of Subjects Who Achieve Clinical Remission at Week 8 Using Modified Mayo Score.	The modified Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 9 points and consists of 3 subscores (stool frequency, rectal bleeding, endoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally.; Clinical remission on the modified Mayo score was defined as a Mayo stool frequency subscore of = 1, Mayo rectal bleeding subscore of 0 and a Mayo endoscopy subscore of = 1.	8 weeks
Secondary	Number of Subjects Who Achieve Clinical Remission at Week 8 Using the Total Mayo Score.	The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally.; Clinical remission on the total Mayo Score is defined as a total Mayo score of = 2, with no individual subscore > 1.	8 weeks
Secondary	Number of Subjects With a Clinical Response on the Modified Mayo Score at Week 8.	The modified Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 9 points and consists of 3 subscores (stool frequency, rectal bleeding, endoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally.; Clinical response on the modified Mayo score at Week 8 was defined as a reduction from the baseline modified Mayo score of = 2 points and = 25%, and a decrease from baseline in rectal bleeding score of = 1 point or absolute rectal bleeding score of = 1 point.	8 weeks
Secondary	Number of Subjects With a Clinical Response on the Total Mayo Score at Week 8.	The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally.; Clinical response on the total Mayo score at Week 8 was defined as a reduction from baseline total Mayo score of = 3 points and = 30%, and a decrease from baseline in rectal bleeding score of = 1 point or absolute rectal bleeding score of = 1 point.	8 weeks
Secondary	Percent Change From Baseline to Week 8 in Fecal Calprotectin in Subjects With Baseline Fecal Calprotectin = 250 µg/g	Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation.	Baseline to Week 8
Secondary	Percent Change From Baseline in Total Mayo Score at Week 8.	Analyzes the change in total Mayo score score between baseline and Week 8 for all randomized subjects who had total Mayo score scores at both baseline and Week 8.; The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally.	Baseline to Week 8