Rheumatoid Arthritis, DMARD-naive and Early Disease Patients Clinical Trial
Official title:
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
| Verified date | December 2017 |
| Source | Rottapharm Biotech |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Completed |
| Enrollment | 248 |
| Est. completion date | January 8, 2019 |
| Est. primary completion date | January 8, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: 1. Male or female aged =18 years. 2. Patients with diagnosis of definite Rheumatoid Arthritis (RA) according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. 3. Disease duration no longer than 1 year (early RA). 4. Patients must be naïve to any DMARDs (csDMARDs, or bDMARDs, or tsDMARDs) other than hydroxychloroquine. 5. Patients with "moderate" disease activity as documented by a Disease Activity Score 28 (DAS28) (C-Reactive Protein - CRP) index score > 3.2. 6. Patients with serum C-Reactive Protein (hsCRP) higher than the upper limit of normal. 7. Patients positive for serum rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA). Exclusion Criteria: 1. 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. 2. History of gastric/duodenal ulcers and gastrointestinal bleeding, or gastrointestinal diseases known to interfere with the absorption or excretion of medications. 3. Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease. 4. 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. 5. Acute hepatitis (during the 3 months preceding the Screening Visit), chronic hepatitis, or HIV infection. 6. History of alcohol or drug abuse, or 7. allergy/sensitivity to lactose. 8. Vaccination with live vaccines during the 6 weeks preceding the Screening Visit. 9. Clinically significant abnormalities in haematology, serum alkaline-phosphatase, gamma-glutamyl-transferase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine clearance, 12-lead ECG. 10. Use of hydroxychloroquine during the 4 weeks preceding the Screening Visit. 11. Treatment with oral corticosteroids, unless maintained at doses equivalent to =10 mg/day prednisone =7 days before the Screening Visit. 12. Use of nonsteroidal anti-inflammatory drugs (NSAIDs). 13. Use of other investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding the Screening Visit. 14. For women of childbearing potential: 1. Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding 2. Failure to agree to practice a highly effective method of contraception. 15. For sexually active men with a female partner of childbearing potential: failure to agree to use contraception. |
| Country | Name | City | State |
|---|---|---|---|
| Czechia | Institute of Rheumatology | Prague |
| Lead Sponsor | Collaborator |
|---|---|
| Rottapharm Biotech |
Czechia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | American College of Rheumatology 20% improvement (ACR20) responder rate | 12 weeks | ||
| Secondary | ACR50 responder rate | 12 weeks | ||
| Secondary | ACR70 responder rate | 12 weeks | ||
| Secondary | Disease Activity Score on 28-joint count (DAS28) | 12 weeks | ||
| Secondary | Clinical Disease Activity Index (CDAI) | 12 weeks | ||
| Secondary | Simplified Disease Activity Index (SDAI) | 12 weeks | ||
| Secondary | ACR/EULAR remission criteria | 12 weeks | ||
| Secondary | Adverse Events | number of patients with Adverse Events | 12 weeks | |
| Secondary | Routine Laboratory determinations | 12 weeks | ||
| Secondary | Pharmacokinetics (PK) of Methotrexate and CR6086 in combination | Main PK endpoint: AUCinf (ng.h/mL). Area under the plasma concentration vs time curve extrapolated to infinity | 12 weeks | |
| Secondary | Biochemical markers | Serum biomarkers of disease activity | 12 weeks | |
| Secondary | Imaging biomarkers | Dynamic Contrast-Enhanced MRI (DCE-MRI) | 12 weeks |