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

Phase 1

• Conditions: Rheumatoid Arthritis; MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2016-004834-11-PL
• Lead Sponsor: Rottapharm Biotech S.r.l.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-17
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 240

Inclusion Criteria

1. Signed and dated informed consent obtained before undergoing any trial-specific procedure.
2. Male or female aged =18 years.
3. Patients with definite RA diagnosis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
4. Disease duration no longer than 1 year (early RA). Disease duration is defined as the patient self-reported duration of signs and symptoms of synovitis (e.g. pain, swelling, tenderness) of any joints.
5. Patients must be naïve to any DMARDs (csDMARDs, or bDMARDs, or tsDMARDs), other than hydroxychloroquine, as long as this is discontinued at least 4 weeks prior to the screening visit.
6. Patients with at least 6/68 tender and 6/66 swollen joints, of which at least one joint must be in the hand/wrist (to be imaged in patients participating into the MRI sub-study).
7. Patients with moderate” disease activity as documented by a Disease Activity Score 28 (DAS28) (C-Reactive Protein – CRP) index score > 3.2.
8. Patients with serum C-reactive protein (hsCRP) higher than the upper limit of normal (ULN), i.e. 3 mg/L.
9. Patients positive for serum rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA).
10. Willing and able to comply with the scheduled study visits, the treatment plan, and all study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

Medical history and Concomitant diseases:
1. Functional class IV of Global Functional Status (GFS) in RA, as defined by the ACR Classification.
2. Rheumatic autoimmune disease other than RA, i.e. systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome).
3. Current inflammatory joint disease other than RA.
4. 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 subject's primary diagnosis of RA or the evaluation of the effect of the study drug.
5. History of gastric/duodenal ulcers and gastrointestinal bleeding.
6. Gastrointestinal diseases known to interfere with the absorption or excretion of medications.
7. Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
8. 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.
9. Acute hepatitis (during the 3 months preceding the Screening Visit), chronic hepatitis (previous documented diagnosis of viral or autoimmune hepatitis, or detection of any unexplained elevation of serum ALT or AST greater than 1.5-fold ULN, at least twice in the 6 months before the Screening Visit) and HIV infection.
10. History of alcohol or drug abuse during the 12 months preceding the Screening Visit.
11. Allergy/hypersensitivity/intolerance to any components in CR6086 and MTX, including excipients such as lactose (patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should be excluded), starch, magnesium stearate, cellulose
12. Vaccination with live vaccines during the 6 weeks preceding the Screening Visit.

Laboratory and examinations
13. Hemoglobin <9 g/dL or Hematocrit <30%
14. White blood cell (WBC) count <3.0 x 10^9/L
15. Absolute neutrophil count <1.2 x 10^9/L
16. Platelet count <100 x 10^9/L
17. Serum alkaline-phosphatase, or gamma-glutamyl-transferase greater than 3-fold ULN; alanine aminotransferase, or aspartate aminotransferase, or total bilirubin greater than 2-fold ULN.
18. Estimated creatinine clearance less than 60 mL/min/1.73 m2 (MDRD).
19. 12-lead electrocardiogram (ECG) with clinically relevant findings, as judged by the Investigator.

Medications
20. Use of hydroxychloroquine during the 4 weeks preceding the Screening Visit.
21. Treatment with oral corticosteroids, unless maintained at doses equivalent to =10 mg/day prednisone =7 days before the Screening Visit. Use of steroids by other administration route before screening visit is allowed, with the exception of i.a. administration during the four weeks preceding the screening visit.
22. Use of non-steroi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the efficacy of oral CR6086 in combination with oral MTX over a 12-week treatment period in DMARD-naïve patients with early RA, in comparison with oral MTX alone.;Secondary Objective: To determine the safety, tolerability and pharmacokinetics of oral CR6086 in combination with oral MTX and the effects on selected biological and imaging biomarkers of disease activity, in comparison with oral MTX alone. ;Primary end point(s): ACR20 responder rate after 12 weeks of combined treatment with CR6086/Placebo and MTX (week 13). ;Timepoint(s) of evaluation of this end point: After 12 weeks of combined treatment with CR6086/Placebo (week 13)