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CF101 Therapy Compared to Methotrexate Therapy for Active Rheumatoid Arthritis

Sponsor
Can-Fite BioPharma (Industry)
Overall Status
Terminated
CT.gov ID
NCT02647762
Collaborator
(none)
244
Enrollment
35
Locations
4
Arms
37
Actual Duration (Months)
7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • Drug: CF101 1 mg
  • Drug: CF101 2 mg
  • Drug: Placebo
  • Drug: MTX
 Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
244 participants
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
Actual Study Start Date :
Oct 30, 2017
Actual Primary Completion Date :
Nov 30, 2020
Actual Study Completion Date :
Nov 30, 2020

Arms and Interventions

Arm Intervention/Treatment
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

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy of oral CF101, BID for 12 weeks to subjects with active rheumatoid arthritis (RA) relative to oral methotrexate (MTX) as assessed by the proportion of subjects achieving a Disease Activity Score (DAS) of Low Disease Activity (LDA) [12 weeks]

      Proportion of subjects achieving Disease Activity Score (DAS) (based on Erythrocyte Sedimentation Rate) of Low Disease Activity (<3.2, where lower scores indicate lower disease activity) at Week 12

    2. Assess the adverse event profile of daily oral CF101 under the conditions of the trial [24 weeks]

      Nature, incidence and severity of treatment-emergent adverse events (TEAEs)

    3. Describe the pharmacokinetics (PK) of CF101 under the conditions of the trial [24 weeks]

      Plasma CF101 levels will be determined

    Secondary Outcome Measures

    1. Determine the efficacy of oral CF101 when administered daily for 24 weeks to subjects with active RA relative to oral MTX, as assessed by the proportion of subjects achieving DAS remission [24 weeks]

      Change and percent change from baseline in DAS28

    2. Explore the relationship between whole blood adenosine A3 receptor (A3AR) expression and treatment response [24 weeks]

      A3AR expression will be assessed on whole blood samples

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    12. Hemoglobin level <9.0 gm/dL

    13. Platelet count <125,000/mm3

    14. White blood cell (WBC) count <3000/mm3

    15. Serum creatinine level outside the central laboratory's normal limits

    16. Liver aminotransferase (ALT and/or AST) levels greater than 2 times the central laboratory's upper limit of normal.

    17. Known or suspected immunodeficiency or human immunodeficiency virus positivity.

    18. Pregnancy, lactation, or inadequate contraception as judged by the Investigator.

    19. Participation in another investigational drug or vaccine trial concurrently or within 30 days prior to Screening.

    20. Active drug or alcohol dependence.

    21. History of malignancy within the past 2 years (excluding excised basal or squamous cell carcinoma of the skin).

    22. 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

    Locations

    Site City State Country Postal Code
    1 Can-Fite Investigational Site #252 Banja Luka Bosnia and Herzegovina
    2 Can-Fite Investigational Site #256 Banja Luka Bosnia and Herzegovina
    3 Can-Fite Investigational Site #253 Mostar Bosnia and Herzegovina
    4 Can-Fite Investigational Site #251 Sarajevo Bosnia and Herzegovina
    5 Can-Fite Investigational Site #255 Tuzla Bosnia and Herzegovina
    6 Can-Fite Investigational Site #751 Barrie Canada
    7 Can-Fite Investigational Site #309 Ashkelon Israel
    8 Can-Fite Investigational Site #302 Haifa Israel
    9 Can-Fite Investigational Site #581 Chisinau Moldova, Republic of
    10 Can-Fite Investigational Site #582 Chisinau Moldova, Republic of
    11 Can-Fite Investigational Site #583 Chisinau Moldova, Republic of
    12 Can-Fite Investigational Site #401 Białystok Poland
    13 Can-Fite Investigational Site #402 Bochnia Poland
    14 Can-Fite Investigational Site #403 Poznań Poland
    15 Can-Fite Investigational Site #559 Brăila Romania
    16 Can-Fite Investigational Site #551 Bucuresti Romania
    17 Can-Fite Investigational Site #552 Bucuresti Romania
    18 Can-Fite Investigational Site #553 Bucuresti Romania
    19 Can-Fite Investigational Site #562 Bucuresti Romania
    20 Can-Fite Investigational Site #564 Bucuresti Romania
    21 Can-Fite Investigational Site #565 Bucuresti Romania
    22 Can-Fite Investigational Site #558 Constanţa Romania
    23 Can-Fite Investigational Site #563 Craiova Romania
    24 Can-Fite Investigational Site #561 Iaşi Romania
    25 Can-Fite Investigational Site #555 Oradea Romania
    26 Can-Fite Investigational Site #554 Timişoara Romania
    27 Can-Fite Investigational Site #212 Belgrad Serbia
    28 Can-Fite Investigational Site #223 Bor Serbia
    29 Can-Fite Investigational Site #219 Kragujevac Serbia
    30 Can-Fite Investigational Site #215 Niš Serbia
    31 Can-Fite Investigational Site #213 Novi Sad Serbia
    32 Can-Fite Investigational Site #222 Pirot Serbia
    33 Can-FIte Investigational Site #221 Sremska Mitrovica Serbia
    34 Can-Fite Investigational Site #220 Zrenjanin Serbia
    35 Can-Fite Investigational Site #214 Šabac Serbia

    Sponsors and Collaborators

    • Can-Fite BioPharma

    Investigators

    • Study Director: Michael H Silverman, MD, Can-Fite BioPharma

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Can-Fite BioPharma
    ClinicalTrials.gov Identifier:
    NCT02647762
    Other Study ID Numbers:
    • CF101-301RA
    First Posted:
    Jan 6, 2016
    Last Update Posted:
    Dec 19, 2020
    Last Verified:
    Mar 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid

    Study Results

    No Results Posted as of Dec 19, 2020