Rheumatoid Arthritis
Conditions
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.
Interventions
DRUGCF101
orally q12h
DRUGPlacebo control
orally q12 hours
Sponsors
Can-Fite BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Bulgaria, Israel
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CF101 1mg CF101 1mg q12 for 12 weeks | 42 |
| Placebo MAtching placebo q12 for 12 weeks | 37 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | hospitalized and decided to stop | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Noncomplience | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | CF101 1mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 9.87 | 61.7 years STANDARD_DEVIATION 6.89 | 59 years STANDARD_DEVIATION 8.92 |
| Sex: Female, Male Female | 32 Participants | 32 Participants | 64 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 42 | 0 / 37 |
| serious Total, serious adverse events | 1 / 42 | 1 / 37 |
Outcome results
Primary
Number of Subjects Achieving an American College of Rheumatology 20 (ACR20) Response (20% Improvement)
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
Time frame: 12 weeks
Population: ITT population, all-cause dropouts considered non-responders
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CF101 1mg | Number of Subjects Achieving an American College of Rheumatology 20 (ACR20) Response (20% Improvement) | 18 Participants |
| Placebo | Number of Subjects Achieving an American College of Rheumatology 20 (ACR20) Response (20% Improvement) | 8 Participants |
p-value: 0.0352t-test, 2 sided
Secondary
Number of Subjects Achieving an ACR50 Response (50% Improvement)
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
Time frame: 12 weeks
Population: ITT population, all-cause dropouts considered non-responders
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CF101 1mg | Number of Subjects Achieving an ACR50 Response (50% Improvement) | 7 Participants |
| Placebo | Number of Subjects Achieving an ACR50 Response (50% Improvement) | 3 Participants |
p-value: 0.2472t-test, 2 sided
Secondary
Number of Subjects Achieving an ACR70 Response (70% Improvement)
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
Time frame: 12 weeks
Population: ITT population, all-cause dropouts considered non-responders
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CF101 1mg | Number of Subjects Achieving an ACR70 Response (70% Improvement) | 4 Participants |
| Placebo | Number of Subjects Achieving an ACR70 Response (70% Improvement) | 1 Participants |
p-value: 0.1972t-test, 2 sided