Oral CF101 Tablets Treatment in Patients With Rheumatoid Arthritis

Phase 2

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: CF101; Drug: Placebo control

• Registration Number: NCT01034306
• Lead Sponsor: Can-Fite BioPharma

Brief Summary

This trial will test the hypothesis that the administration of CF101, a novel anti-inflammatory agent, to patients with rheumatoid arthritis and high A3AR expression at baseline will relieve signs and symptoms of the disease.

Detailed Description

This will be a multi-center, randomized, double-blind, parallel-group, placebo-controlled, study in which patients with active RA and high A3AR expression at baseline will be randomized to the addition of either CF101 1.0 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), 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, 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, and 12.

Study Timeline

• Study First Submitted: 2009-12-16
• Study First Submitted QC: 2009-12-16
• Study First Posted: 2009-12-17
• Study Start: 2010-10
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Results First Submitted: 2015-02-24
• Results First Submitted QC: 2015-02-24
• Results First Posted: 2015-03-09
• Status Verified: 2022-02
• Last Update Submitted: 2022-05-05
• Last Update Posted: 2022-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

Inclusion Criteria

• Males and females ages 18-75 years
• Meet the criteria of the American College of Rheumatology 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 either: (c) Westergren ESR of >=28 mm/hour; OR (d) CRP level above the upper limit of normal for the central reference laboratory
• Elevated PBMC A3AR expression level, defined as >= 1.5-fold over a predetermined normal population standard, following the appropriate DMARD/biologic washout period (see Exclusion Criteria) but within 2 weeks of beginning dosing
• If taking a nonsteroidal anti-inflammatory agent (NSAID), dose has been stable for at least 1 month prior to the A3AR Qualification Visit, 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 A3AR Qualification Visit, and will remain unchanged during protocol participation
• In the Investigator's opinion, the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol
• Negative screening serum pregnancy test for female patients of childbearing potential
• Females of childbearing potential must utilize, throughout the course of the trial, 2 methods of contraception deemed adequate by the Investigator (for example, oral contraceptive pills plus a barrier method)
• All aspects of the protocol explained and written informed consent obtained

Exclusion Criteria

• Receipt of any of the following for at least a 1 month washout period prior to the A3AR Qualification Visit: methotrexate, sulfasalazine, oral or injectable gold, azathioprine, minocycline, penicillamine, anakinra
• Receipt of etanercept for at least a 6 week washout period prior to the A3AR Qualification Visit
• Receipt of chloroquine, hydroxychloroquine, cyclosporine, infliximab, golimumab or adalimumab for at least a 2 month washout period prior to the A3AR Qualification Visit
• Receipt of leflunomide for at least a 2 month washout period prior to the A3AR Qualification Visit, unless patient has undergone cholestyramine washout at least 1 month prior to testing
• Receipt of cyclophosphamide for at least a 6 month period prior to the A3AR Qualification Visit
• Receipt of rituximab at any previous time
• Previous failure to respond to methotrexate or any anti-rheumatic biological agent
• Participation in a previous trial CF101 trial
• Use of oral corticosteroids >10 mg of prednisone, or equivalent, per day
• Change in NSAID dose level for 1 month prior to the A3AR Qualification Visit
• Change in oral corticosteroid dose level during the 1 month prior to the A3AR Qualification Visit
• Receipt of parenteral or intra-articular corticosteroids during the 1 month prior to the A3AR Qualification Visit

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CF101 1 mg	CF101	piclidenoson (CF101) 1 mg tablet oral, Q12h for 12 weeks
Placebo	Placebo control	placebo tablet to match the active, oral dosage, Q12h for 12 weeks

Primary Outcome Measures

Name	Time	Method
Number of Subjects Achieving an American College of Rheumatology 20 (ACR20) Response (20% Improvement)	12 weeks	ACR20 Response is defined as a 20% improvement from baseline in disease: 1. \>20% improvement in tender joint count (TJC), and; 2. \>20% improvement in swollen joint count (SJC), and; 3. \>20% improvement in at least 3 of following 5: 1. Physician global assessment (PGA),; 2. Patient global assessment (PAGA),; 3. Patient pain assessment (PPA),; 4. Patient's assessment of physical function using Health Assessment Questionnaire (HAQ), and; 5. Most improved response of ESR and CRP

Secondary Outcome Measures

Name	Time	Method
Number of Subjects Achieving an ACR50 Response (50% Improvement)	12 weeks	ACR50 Response is defined as a 50% improvement from baseline in disease: 1. \>50% improvement in TJC, and; 2. \>50% improvement in SJC, and; 3. \>50% improvement in at least 3 of following 5: 1. Physician global assessment (PGA),; 2. Patient global assessment (PAGA),; 3. Patient pain assessment (PPA),; 4. Patient's assessment of physical function using Health Assessment Questionnaire (HAQ), and; 5. Most improved response of ESR and CRP
Number of Subjects Achieving an ACR70 Response (70% Improvement)	12 weeks	ACR70 Response is defined as a 70% improvement from baseline in disease: 1. \>70% improvement in TJC, and; 2. \>70% improvement in SJC, and; 3. \>70% improvement in at least 3 of following 5: 1. Physician global assessment (PGA),; 2. Patient global assessment (PAGA),; 3. Patient pain assessment (PPA),; 4. Patient's assessment of physical function using Health Assessment Questionnaire (HAQ), and; 5. Most improved response of ESR and CRP

Trial Locations

Locations (5)

Military Medical Academy; 🇧🇬 Sofia, Bulgaria

UMHAT "Sveti Ivan Rilski", Rheumatoloty Clinic; 🇧🇬 Sofia, Bulgaria

Diagnostic Consultative Center Sofia; 🇧🇬 Sofia, Bulgaria

Barzilai Medical Center; 🇮🇱 Ashkelon, Israel

Multiprofile Hospital for Active Treatment; 🇧🇬 Sofia, Bulgaria