Oral CF101 and Methotrexate Treatment in Rheumatoid Arthritis Patients

NCT ID: NCT00280917

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 254 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2007-04-30

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: NA
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Interventions

CF101

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Can-Fite BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael H Silverman, MD

Role: STUDY_DIRECTOR

BioStrategics Consulting Ltd

Locations

Can-Fite Investigational Site

Peoria, Arizona, United States

Can-Fite Investigational Site

Albany, New York, United States

Can-Fite Invesitigational Site

Cleveland, Ohio, United States

Can-Fite Investigational Site

Perrysburg, Ohio, United States

Can-Fite Investigational Site

Sugar Land, Texas, United States

Can-Fite Investigational Site

Plovdiv, , Bulgaria

Can-Fite Investigational Site

Sofia, , Bulgaria

Can-Fite Investigational Site

Sofia, , Bulgaria

Can-Fite Investigational Site

Stara Zagora, , Bulgaria

Can-Fite Investigational Sites

Afula, , Israel

Can-Fite Investigational Site

Ashkelon, , Israel

Can-Fite Investigational Site

Beer Yaakov, , Israel

Can-Fite Investigational Site

Haifa, , Israel

Can-Fite Investigational Site

Haifa, , Israel

Can-Fite Investigational Site

Jerusalem, , Israel

Can-Fite Investigational Site

Jerusalem, , Israel

Can-Fite Investigational Site

Jerusalem, , Israel

Can-Fite Investigational Site

Kfar Saba, , Israel

Can-Fite Investigational Site

Tel Litwinsky, , Israel

Can-Fite Investigational Site

Bialystok, , Poland

Can-Fite Investigational Site

Lublin, , Poland

Can-Fite Investigational Site

Sopot, , Poland

Can-Fite Investigational Site

Szczecin, , Poland

Can-Fite Investigational Site

Brasov, , Romania

Can-Fite Investigational Site

Bucharest, , Romania

Can-Fite Investigational Site

Bucharest, , Romania

Can-Fite Investigational Site

Cluj-Napoca, , Romania

Can-Fite Investigational Site

Iași, , Romania

Can-Fite Investigational Site

Belgrade, , Serbia

Can-Fite Investigational Site

Niška Banja, , Serbia

Can-Fite Investigational Site

Zemun, , Serbia

Can-Fite Investigational Site

Kiev, , Ukraine

Can-Fite Investigational Site

Kiev, , Ukraine

Can-Fite Investigational Site

Kiev, , Ukraine

Can-Fite Investigational Site

Kiev, , Ukraine

Countries

United States; Bulgaria; Israel; Poland; Romania; Serbia; Ukraine

References

Szabo C, Scott GS, Virag L, Egnaczyk G, Salzman AL, Shanley TP, Hasko G. Suppression of macrophage inflammatory protein (MIP)-1alpha production and collagen-induced arthritis by adenosine receptor agonists. Br J Pharmacol. 1998 Sep;125(2):379-87. doi: 10.1038/sj.bjp.0702040.

Reference Type: BACKGROUND

PMID: 9786512 (View on PubMed)

Baharav E, Bar-Yehuda S, Madi L, Silberman D, Rath-Wolfson L, Halpren M, Ochaion A, Weinberger A, Fishman P. Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models. J Rheumatol. 2005 Mar;32(3):469-76.

Reference Type: BACKGROUND

PMID: 15742438 (View on PubMed)

Other Identifiers

CF101-202RA

Identifier Type: -

Identifier Source: org_study_id