Oral CF101 and Methotrexate Treatment in Rheumatoid Arthritis Patients

Phase 2

Completed

Conditions: Rheumatoid Arthritis

Registration Number: NCT00280917

Lead Sponsor: Can-Fite BioPharma

Brief Summary: This trial will test the hypothesis that the addition of CF101, a novel anti-inflammatory agent, will improve the clinical condition of patients with rheumatoid arthritis who still have active joint inflammation despite taking methotrexate for at least 6 months.

Detailed Description: This will be a multi-center, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study in which patients with active RA despite receiving methotrexate for at least 6 months (at unchanged doses for \>=2 months) will be randomized to the addition of either CF101 0.1 mg, CF101 1 mg, CF101 4 mg, or placebo given orally q12h for 12 weeks. Screening examinations will occur within 1 month prior to dosing. Washout of other disease-modifying antirheumatic drugs (DMARDs) (with the exception of hydroxychloroquine), including biological agents, will occur prior to dosing; if washout is necessary, patients must re-qualify for inclusion following the washout. Doses of nonsteroidal anti-inflammatory drugs (NSAIDS) and corticosteroids must be stable for \>=1 month prior to dosing and remain so during protocol participation. Disease activity will be assessed using swollen and tender joint counts, duration of morning stiffness, physician and patient global assessments (by visual analog scale, VAS), patient reported pain (by VAS), a Health Assessment Questionnaire (HAQ) Disability Index (DI), Westergren erythrocyte sedimentation rate (ESR, Screening, Weeks 0 and12), and C-reactive protein (CRP) levels. Assessments will take place at Screening, Baseline (Week 0), and at Weeks 2, 4, 8, 12, and 14.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 254

Inclusion Criteria

Males and females ages 18-75 years
Meet the criteria of the American Rheumatism Association for RA (Arnett FC et al. Arthritis Rheum 1988;31:315-324, Appendix 1)
Not bed- or wheelchair-bound
Active RA, as indicated by the presence of (a) >=6 swollen joints (28 joint count); AND (b) >=6 tender joints (28 joint count); AND at least one of the following: (c) Westergren ESR of >=28 mm/hour; OR (d) CRP level above the upper limit of normal for the central reference laboratory; OR (e) morning stiffness for >=45 minutes
Treatment with weekly oral or parenteral methotrexate for >=6 months prior to baseline
Methotrexate route of administration has been unchanged for >=2 months prior to baseline
Dose of methotrexate has been stable at 15-25 mg/week for >=2 months, and is expected to remain stable throughout the study; the stable dose of methotrexate may alternatively be 10-12.5 mg/week if documented toxicity has precluded a higher dose
If taking hydroxychloroquine, administration duration has been >=3 months and dose has been stable for >=2 months prior to baseline
If taking a nonsteroidal anti-inflammatory agent (NSAID), dose has been stable for at least 1 month prior to baseline, and will remain unchanged during protocol participation
If taking an oral corticosteroid, dose is <=10 mg/day prednisone or equivalent, has been stable for at least 1 month prior to the washout period, and will remain stable through the washout and entire treatment and follow-up period
Absence of clinically significant findings, such as interstitial pneumonitis or active pulmonary infection, on chest X-ray taken within 6 months prior to screening

Exclusion Criteria

Receipt of any of the following for at least a 1 month washout period prior to dosing: sulfasalazine, oral or injectable gold, azathioprine, minocycline, penicillamine, anakinra
Receipt of etanercept for at least a 6 week period prior to dosing
Receipt of cyclosporine, infliximab or adalimumab for at least a 2 month period prior to dosing
Receipt of leflunomide for at least a 2 month period prior to screening, unless patient has undergone cholestyramine washout at least 1 month prior to dosing
Receipt of cyclophosphamide for at least a 6 month period prior to dosing
Receipt of rituximab at any previous time
Receipt of CF101 in a previous trial
Use of oral corticosteroids >10 mg of prednisone, or equivalent, per day
Change in NSAID dose level for 1 month prior to dosing
Change in oral corticosteroid dose level during the 1 month prior to, or during, the washout period
Change in hydroxychloroquine dose level during the 2 months prior to, or during, the washout period
Receipt of parenteral or intra-articular corticosteroids during the 1 month prior to, or during, the washout period
Presence or history of uncontrolled asthma
Presence or history of uncontrolled arterial hypertension or symptomatic hypotension
Significant cardiac arrhythmia or conduction block, congestive heart failure, or any other evidence of clinically significant heart disease; other clinically significant findings on screening electrocardiogram (ECG)
Hemoglobin level <9.0 gm/L
Platelet count <125,000/mm3
White blood cell count <3000/mm3
Serum creatinine level outside the laboratory's normal limits
Liver aminotransferase levels greater than 1.2 times the laboratory's upper limit of normal
Known or suspected immunodeficiency or human immunodeficiency virus positivity
Pregnancy, lactation, or inadequate contraception as judged by the Investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
ACR Efficacy Criteria	12 weeks	ACR 20 response (20% improvnent in RA based on swollen and tender joint counts, physician and patient global assessments of disease activity, a patient pain score) at endpoint (Week 12), with all-cause dropouts considered as nonresponders (nonresponder imputation) in the Intent-To-Treat (ITT) population

Secondary Outcome Measures

Name	Time	Method
Safety	12 weeks	Vital signs and weight, physical examinations, adverse event (AE) reporting, clinical laboratory testing, including liver function, renal function, complete blood count and clinical chemistries, urinalysis, and hematologic testing and 12-lead resting ECGs
ACR Criteria Components	12 weeks	ACR 20 response at all visits in the evaluable population and ACR 50 and ACR 70 responses at all visits in the ITT and evaluable populations using both nonresponder imputation and Last Observation Carried Forward (LOCF) analyses; change and percent change from baseline at each visit in the ITT and evaluable populations, analyzed using LOCF, in ACR response components \[tender joint count, swollen joint count, patient assessment of pain by VAS, patient global assessment of disease activity by VAS, physician global assessment of disease activity by VAS, HAQ DI, CRP (by central laboratory, using an standard-sensitivity assay capable of detecting changes below the upper limit of normal) and ESR\], Disease Activity Score (DAS28), and duration of morning stiffness.

Trial Locations

Locations (3): Can-Fite Invesitigational Site
🇺🇸
Cleveland, Ohio, United States
Can-Fite Investigational Site
🇺🇦
Kiev, Ukraine
Can-Fite Investigational Sites
🇮🇱
Afula, Israel