NCT03341962

Phase 2 Dose-finding IMU-838 for Ulcerative Colitis

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Efficacy and Safety of IMU-838 for Induction and Maintenance Therapy in Moderate-to-severe Ulcerative Colitis

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 263 (actual)
• Sponsor: Immunic AG · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-finding study to evaluate the efficacy and safety of IMU-838 for induction and maintenance therapy with an option for open-label treatment extension in moderate-to-severe ulcerative colitis (CALDOSE-1).

Detailed description

The investigational medicinal product (IMP) IMU-838 (vidofludimus calcium) is a new compound that selectively inhibits the human enzyme dihydroorotate dehydrogenase (DHODH). Dihydroorotate dehydrogenase plays a major role in the de-novo pyrimidine synthesis and is specifically expressed at high levels in proliferating or activated lymphocytes. Resting lymphocytes satisfy their pyrimidine requirements through a DHODH-independent salvage pathway. Thus, IMU-838-mediated DHODH inhibition selectively affects activated, rapidly proliferating lymphocytes. The metabolic stress secondary to DHODH inhibition leads to a reduction of pro-inflammatory cytokine release including interleukin (IL)-17 (IL-17A and IL-17F) and interferon gamma (IFNγ), and to an increased apoptosis in activated lymphocytes. This is a phase 2, multicenter, randomized, double-blind, and placebo-controlled trial in patients with moderate-to-severe UC with an option for open-label treatment extension. The study comprises a blinded induction phase to establish the optimal dose of IMU-838 to induce response and remission, a blinded maintenance phase to evaluate the potential of IMU-838 to maintain remission until Week 50, and an open-label treatment extension arm for all patients who discontinue the blinded phase as scheduled or prematurely, subject to certain restrictions. A subset of patients will undergo a pharmacokinetic (PK) period at the start of the open-label period to establish a full single-dose PK profile.

Conditions

• Ulcerative Colitis

Interventions

Type	Name	Description
DRUG	IMU-838	IMU-838 tablet
DRUG	Placebo	Tablets manufactured to mimic IMU-838 tablets

Timeline

• Start date: 2018-03-15
• Primary completion: 2022-11-16
• Completion: 2022-11-16
• First posted: 2017-11-14
• Last updated: 2024-03-05
• Results posted: 2024-03-05

Locations

131 sites across 19 countries: United States, Albania, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czechia, Georgia, Netherlands, North Macedonia, Poland, Portugal, Romania, Russia, Serbia, Spain, Turkey (Türkiye), Ukraine, United Kingdom

Regulatory

• FDA-regulated drug study