Rheumatoid Arthritis
Conditions
Brief summary
This will be a 12-week, double-blind, randomized, placebo-controlled, parallel group, multicenter study to evaluate the safety, efficacy, and PK of oral administration of PG-760564 in adult patients with active RA receiving treatment with MTX. Two oral doses of PG-760564 will be evaluated: 25 mg BID and 100 mg BID. The study will consist of a screening visit followed by a washout period for all disease modifying antirheumatic drugs (DMARDs) and anti-cytokine therapies except MTX. After the washout period, patients determined to be eligible will be randomized to receive either 25 mg BID or 100 mg BID of oral PG-760564, or placebo for 12 weeks. There will be 6 treatment visits and a follow-up visit 4 weeks after the last treatment visit. The primary efficacy endpoint will be the proportion of patients meeting the ACR 20 response criteria after 12 weeks of treatment.
Detailed description
The study will be conducted in North America and Europe at approximately 50 to 60 sites. Approximately 270 patients will be randomized, of which 189 are expected to complete the study. The study will consist of a screening visit followed by a washout period for all disease modifying antirheumatic drugs (DMARDs) and anti-cytokine therapies except MTX. The washout period will be 4 weeks for sulfasalazine, hydroxychloroquine, azathioprine, D-penicillamine, etanercept, and anakinra, 8 weeks for gold, infliximab, and adalimumab, and 12 weeks for abatacept. After the washout period, the patients determined to be eligible will be randomized to receive either 25 mg BID or 100 mg BID of oral PG-760564, or placebo for 12 weeks. There will be 6 treatment visits (Weeks 1, 2, 4, 6, 8, and 12) and a follow-up visit 4 weeks after the last treatment visit (Week 16). Patients will not initiate new therapies until after the 4-week follow-up is completed. Liver function tests will be evaluated at every visit. The primary efficacy endpoint will be the proportion of patients meeting the ACR 20 response criteria after 12 weeks of treatment.
Interventions
DRUGPG-760564
100 mg BID, of oral PG-760564
DRUGPlacebo dose
placebo, BID, oral for 12 weeks
Sponsors
Procter and Gamble
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Meet American College of Rheumatology (ACR) criteria for Rheumatoid Arthritis * Disease duration of at least 6 months * Must be treated with Methotrexate for at least 24 weeks * At least 6 swollen joints and 6 tender joints * Washout required for other Disease Modifying Anti-rheumatic Drugs (DMARDs) * Women of childbearing age and all males must use acceptable method of birth control
Exclusion criteria
* Tuberculosis * Malignancies * Abnormal electrocardiograms as described in the protocol * Current infection or recurrent infections or immunodeficiency * Liver diseases and abnormalities in liver function tests as described in the protocol * Autoimmune diseases other than RA except Sjogren's syndrome secondary to RA; * History of demyelization diseases * Any condition that in the opinion of the investigator could be detrimental to patients enrolling in the study including clinically important changes in laboratory values and other diseases described in the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Meeting American College of Rheumatology 20 Response Criteria (ACR20) at 12weeks | 12 weeks | percent, relative to baseline, of patients meeting the American College of Rheumatology 20 response criteria (ACR20) at 12weeks |
Countries
Czechia, Hungary, Netherlands, Poland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo, oral dose, BID | 85 |
| 25 mg PG-760564 BID 25 mg BID, of oral PG-760564 | 85 |
| 100 mg PG-760564 BID 100 mg BID, of oral PG-760564 | 86 |
| Total | 256 |
Baseline characteristics
| Characteristic | Placebo | 25 mg PG-760564 BID | 100 mg PG-760564 BID | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 7 Participants | 7 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 75 Participants | 78 Participants | 79 Participants | 232 Participants |
| Age Continuous | 51.52 years STANDARD_DEVIATION 11.04 | 50.39 years STANDARD_DEVIATION 11.68 | 54.70 years STANDARD_DEVIATION 9.31 | 52.21 years STANDARD_DEVIATION 10.83 |
| Region of Enrollment Czech Republic | 18 participants | 23 participants | 16 participants | 57 participants |
| Region of Enrollment Hungary | 10 participants | 9 participants | 12 participants | 31 participants |
| Region of Enrollment Poland | 45 participants | 42 participants | 49 participants | 136 participants |
| Region of Enrollment United Kingdom | 3 participants | 0 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 9 participants | 11 participants | 9 participants | 29 participants |
| Sex: Female, Male Female | 64 Participants | 65 Participants | 66 Participants | 195 Participants |
| Sex: Female, Male Male | 21 Participants | 20 Participants | 20 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 85 | 2 / 85 | 5 / 86 |
| serious Total, serious adverse events | 1 / 85 | 4 / 85 | 6 / 86 |
Outcome results
Primary
Proportion of Patients Meeting American College of Rheumatology 20 Response Criteria (ACR20) at 12weeks
percent, relative to baseline, of patients meeting the American College of Rheumatology 20 response criteria (ACR20) at 12weeks
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Patients Meeting American College of Rheumatology 20 Response Criteria (ACR20) at 12weeks | 60 percent meeting ACR 20 |
| 25 mg PG-760564 BID | Proportion of Patients Meeting American College of Rheumatology 20 Response Criteria (ACR20) at 12weeks | 56 percent meeting ACR 20 |
| 100 mg PG-760564 BID | Proportion of Patients Meeting American College of Rheumatology 20 Response Criteria (ACR20) at 12weeks | 54 percent meeting ACR 20 |
p-value: 0.98280% CI: [0.56, 1.38]Cochran-Mantel-Haenszel
p-value: 0.66680% CI: [0.5, 1.25]Cochran-Mantel-Haenszel