NCT03163966

A Study of the EP4 Antagonist CR6086 in Combination With Methotrexate, in DMARD-naïve Patients With Early Rheumatoid Arthritis

A Randomized, Double Blind, Placebo-controlled, Dose Response, Phase II, Multicentre Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of Oral CR6086 Administered at the Doses of 30, 90 or 180 mg Bid for 12 Weeks in Combination With Methotrexate, in DMARD-naïve Patients With Early Rheumatoid Arthritis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 248 (actual)
• Sponsor: Rottapharm Biotech · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

CR6086 is a new, potent and selective, orally available, small molecule prostaglandin EP4 receptor antagonist, endowed with immunomodulatory properties. The pharmacological properties of CR6086, along with its oral bioavailability, predictable pharmacokinetics and good safety, make it the ideal candidate to be tested alone or in combination with methotrexate (MTX) in patients with early Rheumatoid Arthritis who are naïve to Disease-Modifying Antirheumatic Drugs (DMARDs). The compound has indeed the potential to provide a safer and more effective treatment than MTX (or other conventional synthetic DMARDs - csDMARDs), and could significantly improve the proportion of responder patients and avoid/delay the recourse to biological DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs).

Detailed description

There is growing evidence that EP4 receptors play an important role in the altered immune response observed in autoimmune diseases. These findings point to the EP4 receptor as a rational target for the development of novel Disease-Modifying Antirheumatic Drugs (DMARDs)/immunomodulators which, in addition, have direct anti-inflammatory properties. The potential for CR6086 to act as a DMARD was extensively demonstrated in a series of widely accepted models of arthritis in rodents, where oral CR6086 was effective in all the parameters examined, including oedema, clinical arthritis score, and histology. CR6086 performed much better than nonsteroidal anti-inflammatory drugs (NSAIDs, that lack the immunomodulatory properties of an EP4 receptor antagonist and are scarcely effective), better than first-line csDMARDs such as MTX, and similarly to immunosuppressive bDMARDs such as TNF-blockers, or tsDMARDs such as JAK inhibitors. In the present study, CR6086 (or placebo) will be administered in a dose-response fashion for 12 weeks to DMARD-naïve patients with early Rheumatoid Arthritis, in combination with oral MTX. The treatment duration and study design will allow to test the effects of the new treatment on clinical outcomes of disease activity, laboratory biomarkers and imaging parameters.

Conditions

• Rheumatoid Arthritis, DMARD-naive and Early Disease Patients

Interventions

Type	Name	Description
DRUG	CR6086	oral CR6086 capsules
DRUG	Methotrexate	oral Methotrexate tablets
DRUG	Placebo	oral CR6086 Placebo capsules

Timeline

• Start date: 2017-10-05
• Primary completion: 2019-01-08
• Completion: 2019-01-08
• First posted: 2017-05-23
• Last updated: 2021-10-05

Locations

1 site across 1 country: Czechia