Efficacy & Safety in Moderately Active Refractory Ulcerative Colitis Patients

A Multi-centre, Double-blind, Placebo Controlled, Parallel Group, Proof of Concept Study to Evaluate the Efficacy, Safety and Tolerability of KRP203 in Subjects With Moderately Active Refractory Ulcerative Colitis

This study is designed as a proof of concept of KRP203 for induction of remission in ulcerative colitis (UC). The purpose of this study is to evaluate clinical benefit of KRP203 in subjects with moderately active refractory ulcerative colitis.

The study will provide safety and tolerability data in this subject population up to eight weeks of treatment with KRP203. Additionally, this study will evaluate the duration of a clinical response to KRP203 by following up responding subjects for an additional 12 weeks.

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: KRP203; Drug: Placebo matching KRP203

Detailed Description

This is a multi-centre, double-blind, placebo controlled, parallel group, proof of concept study to evaluate the efficacy, safety and tolerability of KRP203 in subjects with moderately active refractory ulcerative colitis subjects. In total, approximately 72 subjects will be randomized into the study.

After 30 patients have completed the 8 week treatment period with KRP203 or placebo, there will be an interim analysis to determine preliminary efficacy. The study will consist of up to 28 day screening period (day -35 to -8), baseline period (day -7 to day -1), treatment period (day 1 to day 56), follow-up period and study completion.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Germany
  • Frankfurt am Main, Germany, 60318
    • Novartis Investigative Site
  • Hamburg, Germany, 20148
    • Novartis Investigative Site
  • Köln, Germany, 51103
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1083
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
• Sweden
  • Stockholm, Sweden, 116 91
    • Novartis Investigative Site
  • Stockholm, Sweden, SE-141 86
    • Novartis Investigative Site
  • Uppsala, Sweden, 751 85
    • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Zurich, Switzerland, 8091
    • Novartis Investigative Site
• United Kingdom
  • Nottingham, United Kingdom, NG7 2UH
    • Novartis Investigative Site
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Active disease defined by partial Mayo score and modified Baron score with disease extending at least 25 cm from the anal verge
• Subjects must have inadequately responded or intolerance to 5-ASA therapy

Exclusion Criteria:

• Subjects receiving treatment for UC (other than 5-ASAs and steroids) within the time frame mentioned in protocol
• Past or recent history of significant medical illness and/or clinically significant lab abnormalities including but not limited to hematology, clinical chemistry, urine analysis, ECG abnormalities, HIV, Hepatitis B/C
• Presence or history of underlying metabolic, endocrine, hematologic, pulmonary, ophthalmic, cardiac, blood, renal, hepatic, infectious, psychiatric or any medically unstable condition, as assessed by the primary treating physician which, in the opinion of the investigator, would immunocompromise the subject and/or place the subject at unacceptable risk for participation in a study of an immunomodulatory therapy Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo matching KRP203
Experimental: KRP203; Experimental Edit Experimental	Drug: KRP203

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in clinical remission rate	Difference between clinical remission rate of subjects on KRP203 versus placebo	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Safety and tolerability of KRP203 assessed by the number of subjects with adverse events where KRP203 is given as an oral drug for 8 weeks once a day in ulcerative colitis subjects	8 weeks
Pharmacokinetic properties of KRP203 at steady-state using whole blood samples in patients with ulcerative colitis subjects		8 weeks
Difference in pharmacokinetic levels	To explore the relationship between KRP203 and KRP203-P pharmacokinetic levels and clinical efficacy outcomes such as the partial Mayo score and endoscopic modified Baron Score	12 weeks
Assessment of the pharmacodynamic effect of KRP203 on absolute lymphocyte count and leukocyte subsets in ulcerative colitis subjects		12 weeks
Change in markers of inflammation	Measure of the effect of KRP203 on markers of inflammation, including but not limited to ESR, CRP and fecal calprotectin/ lactoferrin as well as histopathological markers of gut mucosa using biopsy samples in ulcerative colitis subjects	12 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: May 12, 2011
• First Submitted That Met QC Criteria: June 16, 2011
• First Posted (Estimate): June 17, 2011

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 8, 2020
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Ulcerative colitis; Inflammatory Bowel disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: CKRP203A2201; 2010-019970-33 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No