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CF101 Therapy Compared to Methotrexate Therapy for Active Rheumatoid Arthritis

This study is not yet open for participant recruitment.
Verified March 2016 by Can-Fite BioPharma
Sponsor:
ClinicalTrials.gov Identifier:
NCT02647762
First Posted: January 6, 2016
Last Update Posted: June 2, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Can-Fite BioPharma
  Purpose
This trial will test the hypothesis that the administration of CF101, a novel anti-inflammatory agent, to patients with rheumatoid arthritis will relieve signs and symptoms of the disease. CF101 effect will be in comparison to MTX in this study population.

Condition Intervention Phase
Rheumatoid Arthritis Drug: CF101 1 mg Drug: CF101 2 mg Drug: Placebo Drug: MTX Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Active- and Placebo-controlled, Parallel-group Trial to Evaluate the Efficacy and Safety of CF101 Compared to Methotrexate in the Treatment of Early Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Can-Fite BioPharma:

Primary Outcome Measures:
  • Proportion of subjects achieving DAS Low Activity Score (LDA) (<3.2) response at Week 12 [ Time Frame: 12 weeks ]
    Proportion of subjects achieving DAS Low Activity Score (LDA) (<3.2) response at Week 12, with all-cause dropouts considered as non-responders, in the Intent-To-Treat (ITT) population


Secondary Outcome Measures:
  • Swollen joint count [ Time Frame: 12 weeks ]
    Change and percent change from baseline in swollen joint count at each visit

  • Tender joint count [ Time Frame: 12 weeks ]
    Change and percent change from baseline in tender joint count at each visit

  • Physician global assessment [ Time Frame: 12 weeks ]
    Percent change from baseline in physician global assessment at each visit

  • Patient's global assessment [ Time Frame: 12 weeks ]
    Change and percent change from baseline in patient's global assessment at each visit

  • Patient's pain score [ Time Frame: 12 weeks ]
    Change and percent change in patient's pain score at each visit

  • HAQDI score [ Time Frame: 12 weeks ]
    Change and percent change from baseline in HAQDI at each visit

  • DAS28 [ Time Frame: 12 weeks ]
    Change and percent change from baseline in DAS28

  • A3AR expression levels and patient's response to the drug [ Time Frame: 12 weeks ]
    Explore the relationship between white blood cell (WBC) adenosine A3 receptor (A3AR) expression and treatment response, by taking WBC sample at baseline and week 12.

  • Proportion of subjects meeting ACR 20 criteria at each visit [ Time Frame: 12 weeks ]
    The proportion of subjects meeting ACR 20 criteria will be analyzed using the normal approximation to the binomial distribution at each visit. Analyses of other secondary efficacy variables will be performed using analysis of covariance (ANCOVA) at each visit.

  • Proportion of subjects meeting ACR 50 criteria at each visit [ Time Frame: 12 weeks ]
    The proportion of subjects meeting ACR 50 criteria will be analyzed using the normal approximation to the binomial distribution at each visit. Analyses of other secondary efficacy variables will be performed using analysis of covariance (ANCOVA) at each visit.

  • Proportion of subjects meeting ACR 70 criteria at each visit [ Time Frame: 12 weeks ]
    The proportion of subjects meeting ACR 70 criteria will be analyzed using the normal approximation to the binomial distribution at each visit. Analyses of other secondary efficacy variables will be performed using analysis of covariance (ANCOVA) at each visit.


Other Outcome Measures:
  • CF101 Maximum concentration (Cmax) [ Time Frame: 12 weeks ]
    CF101 maximum concentration (Cmax) on Weeks 0, 8 and 12

  • CF101 minimum concentration (Cmin) [ Time Frame: 12 weeks ]
    CF101 minimum concentration (Cmin) on Weeks 0, 8 and 12

  • CF101 area under the curve (AUC) [ Time Frame: 12 weeks ]
    CF101 area under the curve (AUC) on Weeks 0, 8 and 12

  • CF101 peak plasma levels [ Time Frame: 12 weeks ]
    CF101 peak plasma levels on Weeks 8 and 12


Estimated Enrollment: 525
Study Start Date: September 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CF101 1mg
CF101 1mg, orally q12 hours
Drug: CF101 1 mg
CF101 tablets, 1mg BID for 12 weeks
Other Names:
  • IB-MECA
  • Piclidenosone
Experimental: CF101 2mg
CF101 2mg, orally q12 hours
Drug: CF101 2 mg
CF101 tablets, 2 mg BID for 12 weeks
Other Names:
  • IB-MECA
  • Piclidenosone
Active Comparator: MTX once weekly
MTX 5 mg tablets, given once weekly at 10 mg/week (2 tablets) for the first 2 weeks, then 15 mg/week (3 tablets) for the next 2 weeks, then 20 mg/week (4 tablets) thereafter.
Drug: MTX
MTX 5 mg tablets, given once weekly at 10 mg/week (2 tablets) for the first 2 weeks, then 15 mg/week (3 tablets) for the next 2 weeks, then 20 mg/week (4 tablets) thereafter, for 12 weeks.
Placebo Comparator: Placebo
Placebo control , orally q12 hours
Drug: Placebo
Placebo tablets, 1mg BID for 12 weeks

Detailed Description:

This will be a randomized, double-blind, active- and placebo-controlled, parallel-group study in subjects with clinically active RA but who are MTX-naïve. Subjects who meet enrollment criteria will be randomized to 1 of 4 groups in a 2:2:2:1 ratio: CF101 1 mg, CF101 2 mg, MTX, or matching placebo tablets. CF101 or matching placebo will be administered every 12 hours for up to 24 weeks on treatment. MTX or matching placebo will be administered once a week Screening examinations will occur within 6 weeks prior to dosing. The following conventional drugs for RA treatment must be stable for the respective designated periods prior to the Screening Visit and must remain so during protocol participation: nonsteroidal anti-inflammatory drugs (NSAIDS), and corticosteroids for >1 month. All subjects will receive oral folate (minimum dose 5 mg/week) or oral folinic acid (up to 10 mg/week), based on the Investigator's preference.

Disease activity will be assessed using swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and CRP. Efficacy will be assessed by Disease Activity Score 28 using the erythrocyte sedimentation rate (DAS28-ESR), ACR response criteria and European League Against Rheumatism (EULAR) response criteria : swollen and tender joint counts, physician global assessment (by visual analog scale, patient global assessment , patient reported pain, a Health Assessment Questionnaire (HAQ) Disability Index (DI) , Westergren ESR levels, and CRP levels. Assessments will occur at Screening, Baseline (Week 0), and Weeks 4, 8, 12 16, 20, and 24. At Weeks 12, 16, and 20, any subject who has not experienced at least 20% improvement in both the number of swollen and number of tender joints will be given rescue therapy with open-label oral MTX and followed through Week 24.

PK will be assessed in a subgroup of approximately 100 subjects at Week 0, Week 8, and Week 12. All subjects in the PK cohort will have samples collected for PK at time 0, and each subject will have additional samples drawn at 2 of the following post-dose time points: 1, 2, 3, 4, 6, and 8 hours. Whole blood sample for A3AR expression will be assessed in approximately 100 subjects at selected sites at Screening and Week 12, or end of dosing, if occurring before Week 12.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females ages 18-75 years.
  2. Meet the criteria of the American College of Rheumatology for RA (Arnett FC et al. Arthritis Rheum 1988;31:315-324, Appendix 1).
  3. Not bed- or wheelchair-bound.
  4. Active RA, as indicated by EULAR Disease Activity Score (Fransen, vanRiel, 2005, DAS28, 2015) (DAS28) >3.2.
  5. Demonstrate at least 6 swollen and at least 6 tender joints.
  6. If taking an NSAID, dose has been stable for at least 1 month prior to the Screening Visit, and will remain unchanged during protocol participation.
  7. If taking an oral corticosteroid, dose is <10 mg/day prednisone or equivalent, has been stable for at least 1 month prior to the Screening Visit, and will remain unchanged during protocol participation.
  8. 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.
  9. Negative Screening serum pregnancy test for female subjects of childbearing potential.
  10. 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).
  11. All aspects of the protocol explained and written informed consent obtained.

Exclusion Criteria:

  1. Prior receipt of MTX.
  2. Prior receipt of >1 regimen of synthetic small-molecule DMARDs.
  3. Receipt of any non-MTX synthetic small-molecule DMARDs (including but not limited to sulfasalazine, chloroquine/hydroxychloroquine, azathioprine, and/or leflunomide) for at least 1 month prior to the Screening Visit or concomitantly during the trial.
  4. Receipt of tofacitinib at any time during the 4-week period prior to the Screening Visit or concomitantly during the trial.
  5. Receipt of a biologic anti-rheumatic agent (including, but not limited to, etanercept, abatacept, infliximab, golimumab, adalimumab, tocilizumab, certolizumab, and rituximab) at any time prior to or concomitantly during the trial.
  6. Levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody that are both >3 times the upper limit of the laboratory normal value at the Screening Visit.
  7. Receipt of parenteral or intra-articular corticosteroids during the 1 month prior to the Screening Visit.
  8. Participation in a previous trial CF101 trial.
  9. Presence or history of uncontrolled arterial hypertension or symptomatic hypotension.
  10. Heart disease which is, in the Investigator's judgment, clinically significant or unstable, including coronary artery disease, congestive heart failure, uncontrolled arrhythmia, or other significant findings on Screening electrocardiogram (ECG).
  11. Clinical laboratory abnormalities at the Screening Visit as follows:

    1. Hemoglobin level <9.0 gm/dL
    2. Platelet count <125,000/mm3
    3. White blood cell (WBC) count <3000/mm3
    4. Serum creatinine level outside the central laboratory's normal limits
    5. Liver aminotransferase (ALT and/or AST) levels greater than 2 times the central laboratory's upper limit of normal.
  12. Known or suspected immunodeficiency or human immunodeficiency virus positivity.
  13. Pregnancy, lactation, or inadequate contraception as judged by the Investigator.
  14. Participation in another investigational drug or vaccine trial concurrently or within 30 days prior to Screening.
  15. Active drug or alcohol dependence.
  16. History of malignancy within the past 2 years (excluding excised basal or squamous cell carcinoma of the skin).
  17. Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02647762


Contacts
Contact: Zivit Harpaz 972-3-9241114 zivit@canfite.co.il

Locations
Israel
Barzilai Medical Cente Not yet recruiting
Ashkelon, Israel
Contact: Tatiana Reitblat, MD         
Rambam Medical Center Not yet recruiting
Israel, Israel
Contact: Alexandra Gurman-Balbir, MD         
Sponsors and Collaborators
Can-Fite BioPharma
Investigators
Study Director: Michael H Silverman, MD Can-Fite BioPharma
  More Information

Responsible Party: Can-Fite BioPharma
ClinicalTrials.gov Identifier: NCT02647762     History of Changes
Other Study ID Numbers: CF101-301RA
First Submitted: December 16, 2015
First Posted: January 6, 2016
Last Update Posted: June 2, 2016
Last Verified: March 2016

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors