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

NCT03163966 | Completed Phase 2 DMC

• 1 other identifier: CR6086-2-02
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Rheumatoid Arthritis, DMARD-naive and Early Disease Patients

Outcome Measures

Primary Outcomes (1)

• American College of Rheumatology 20% improvement (ACR20) responder rate

  12 weeks

Secondary Outcomes (11)

• ACR50 responder rate

  12 weeks

• ACR70 responder rate

  12 weeks

• Disease Activity Score on 28-joint count (DAS28)

  12 weeks

• Clinical Disease Activity Index (CDAI)

  12 weeks

• Simplified Disease Activity Index (SDAI)

  12 weeks

Study Arms (4)

CR6086 30 mg

EXPERIMENTAL

CR6086 30 mg bid for 12 weeks as add-on to methotrexate (MTX) once weekly. MTX uptitrated to stable dosing as per standard guidelines

Drug: CR6086; Drug: Methotrexate

CR6086 90 mg

EXPERIMENTAL

CR6086 90 mg bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines

Drug: CR6086; Drug: Methotrexate

CR6086 180 mg

EXPERIMENTAL

CR6086 180 mg bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines

Drug: CR6086; Drug: Methotrexate

Placebo

EXPERIMENTAL

CR6086 matching placebo bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines

Drug: Methotrexate; Drug: Placebo

Interventions

CR6086 DRUG

oral CR6086 capsules

CR6086 180 mg; CR6086 30 mg; CR6086 90 mg

Methotrexate DRUG

oral Methotrexate tablets

CR6086 180 mg; CR6086 30 mg; CR6086 90 mg; Placebo

Placebo DRUG

oral CR6086 Placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥18 years.
• Patients with diagnosis of definite Rheumatoid Arthritis (RA) according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
• Disease duration no longer than 1 year (early RA).
• Patients must be naïve to any DMARDs (csDMARDs, or bDMARDs, or tsDMARDs) other than hydroxychloroquine.
• Patients with "moderate" disease activity as documented by a Disease Activity Score 28 (DAS28) (C-Reactive Protein - CRP) index score \> 3.2.
• Patients with serum C-Reactive Protein (hsCRP) higher than the upper limit of normal.
• Patients positive for serum rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA).

You may not qualify if:

• Rheumatic autoimmune disease other than RA, or current inflammatory joint disease other than RA, or non-inflammatory type of musculoskeletal condition (e.g., osteoarthritis or fibromyalgia) that in the Investigator's opinion is symptomatic and/or severe enough to interfere with the study procedures.
• History of gastric/duodenal ulcers and gastrointestinal bleeding, or gastrointestinal diseases known to interfere with the absorption or excretion of medications.
• Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
• Malignancy (with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ) active during the 12 months preceding the Screening Visit.
• Acute hepatitis (during the 3 months preceding the Screening Visit), chronic hepatitis, or HIV infection.
• History of alcohol or drug abuse, or
• allergy/sensitivity to lactose.
• Vaccination with live vaccines during the 6 weeks preceding the Screening Visit.
• Clinically significant abnormalities in haematology, serum alkaline-phosphatase, gamma-glutamyl-transferase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine clearance, 12-lead ECG.
• Use of hydroxychloroquine during the 4 weeks preceding the Screening Visit.
• Treatment with oral corticosteroids, unless maintained at doses equivalent to ≤10 mg/day prednisone ≥7 days before the Screening Visit.
• Use of nonsteroidal anti-inflammatory drugs (NSAIDs).
• Use of other investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding the Screening Visit.
• For women of childbearing potential:
• Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding

Sponsors & Collaborators

• Rottapharm Biotech: lead

Study Sites (1)

Institute of Rheumatology

Prague, Czechia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 23, 2017
• Study Start: October 5, 2017
• Primary Completion: January 8, 2019
• Study Completion: January 8, 2019
• Last Updated: October 5, 2021

Record last verified: 2017-12

Locations

CZ (1)