A randomized, double blind, placebo-controlled, dose response, phase II, multicentretrial to evaluate the efficacy, safety and pharmacokinetics of oral CR6086administered at the doses of 30, 90 or 180 mg bid for 12 weeks in combination withmethotrexate, in DMARD-naïve patients with early rheumatoid arthritis

Phase 1

Conditions: Rheumatoid Arthritis
MedDRA version: 20.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2016-004834-11-GB

Lead Sponsor: Rottapharm Biotech S.r.l.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 248

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 in 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: 0
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

1. Functional class IV of the Global Functional Status in RA, as defined by the ACR
Classification (See Appendix II27).
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. Haemoglobin <9 g/dL or Haematocrit <30%.
14. White blood cell 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 ECG with clinically relevant findings, as judged by the Investigator.
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 NSAIDs if the patient cannot suspend therapy for the whole duration of the
study (from Screening Visit to EOS).
23. Use of other investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding the Screening Visit.
24. For women of childbearing potential:
a. Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding
b. Failure to agree to practice a highly effective method of contraception (see
Section 11.4.2.1), from enrolment up to at least 3 months after the study
end.
25. For sex

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<br>treatment period in DMARD-naïve patients with early RA, in comparison with oral MTX<br>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)

Secondary Outcome Measures

Name	Time	Method

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