Rheumatoid Arthritis
Conditions
Keywords
Signs and Symptoms, Autoimmune Diseases, Joint Diseases, Arthritis, Connective Tissue Diseases, Arthritis, Rheumatoid, Rheumatic Diseases, Predniso(lo)ne
Brief summary
The purpose of the study is to compare the safety and efficacy, with regards to the signs and symptoms, of MR prednisone (Lodotra®) versus placebo in combination with standard Disease Modifying Anti-Rheumatic Drug (DMARD) treatment in patients with active rheumatoid arthritis.
Detailed description
Study with completed results acquired from Horizon in 2024.
Interventions
DRUGMR prednisone
1 x 5 mg daily
DRUGPlacebo
1x daily
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Documented history of RA in agreement with ACR criteria * DMARD treatment for RA greater than or equal to 6 months, with a stable dose greater than or equal to 6 weeks prior to screening visit * Duration of morning stiffness greater than or equal to 45 minutes * greater than or equal to 4 swollen joints (out of 28) * greater than or equal to 4 tender joints (out of 28)
Exclusion criteria
* Suffering from another disease, which requires glucocorticoid treatment during the study period * Synovectomy within 4 months prior to study start * Use of glucocorticoids: * Continued use of systemic glucocorticoids within 4 weeks prior to screening visit * Intermittent use of glucocorticoids within 2 weeks prior to screening visit. * Joint injections within 6 weeks prior to screening visit * Topical glucocorticoids must be stopped at screening visit * Use of biologicals such as: tumor necrosis factor α (TNFα) inhibitors and other compounds within 5 serum half lives prior to screening visit * Pregnancy or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACR 20 Response Rate at Visit 4 | Week 12 | Responders were defined as patients whose improvement from baseline to Visit 4 (Week 12) fulfilled all 3 of the following criteria: * \> 20% reduction in the tender joint count (0-28) * \> 20% reduction in the swollen joint count (0-28) * \> 20% reduction in 3 out of the 5 following additional measures: * Patient's assessment of pain * Patient's global assessment of disease activity * Physician's global assessment of disease activity * Functional Disability Index of the Health Assessment Questionnaire * C-reactive protein or erythrocyte sedimentation rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Reduction of Morning Stiffness | Week 12 | Data for the duration of morning stiffness were obtained from patient diaries. Duration of morning stiffness was the difference between the time of resolution of morning stiffness and the time of wake-up. Duration of morning stiffness is the average of the morning stiffness duration (minutes) over the last 7 days prior to visit day (including day of visit). If more than 4 assessments were missing, then the duration was set to missing. Baseline was the value recorded at Week -1 (Visit 0). |
Countries
Canada, Germany, Hungary, Poland, United Kingdom, United States
Participant flow
Recruitment details
Approximately 350 patients were to be enrolled (at screening, Visit 0), with a minimum of 6 and a maximum of 28 patients at each center. It was planned to randomize (at Visit 1) a total of 294 patients in 50-55 centers in North America and Europe (Germany, Hungary, Poland and UK). First patient enrolled March, 2008; last patient contact May, 2009.
Pre-assignment details
The study consisted of a 1 week screening phase followed by a 12 week double blind treatment phase. In addition to their standard RA medication, patients received placebo during the 1 week screening phase. The purpose of the screening phase was to establish the patient's compliance with study medication and completion of diary entries.
Participants by arm
| Arm | Count |
|---|---|
| NP01 Modified Release (MR) prednisone 5 mg | 231 |
| Placebo | 119 |
| Total | 350 |
Baseline characteristics
| Characteristic | NP01 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 45 Participants | 24 Participants | 69 Participants |
| Age, Categorical Between 18 and 65 years | 186 Participants | 95 Participants | 281 Participants |
| Age, Continuous | 57.1 years STANDARD_DEVIATION 9.89 | 57.5 years STANDARD_DEVIATION 9.55 | 57.2 years STANDARD_DEVIATION 9.76 |
| Region of Enrollment Canada | 8 participants | 5 participants | 13 participants |
| Region of Enrollment Germany | 1 participants | 2 participants | 3 participants |
| Region of Enrollment Hungary | 67 participants | 35 participants | 102 participants |
| Region of Enrollment Poland | 98 participants | 47 participants | 145 participants |
| Region of Enrollment United Kingdom | 9 participants | 3 participants | 12 participants |
| Region of Enrollment United States | 48 participants | 27 participants | 75 participants |
| Sex: Female, Male Female | 192 Participants | 102 Participants | 294 Participants |
| Sex: Female, Male Male | 39 Participants | 17 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 69 / 231 | 49 / 119 |
| serious Total, serious adverse events | 1 / 231 | 2 / 119 |
Outcome results
Primary
ACR 20 Response Rate at Visit 4
Responders were defined as patients whose improvement from baseline to Visit 4 (Week 12) fulfilled all 3 of the following criteria: * \> 20% reduction in the tender joint count (0-28) * \> 20% reduction in the swollen joint count (0-28) * \> 20% reduction in 3 out of the 5 following additional measures: * Patient's assessment of pain * Patient's global assessment of disease activity * Physician's global assessment of disease activity * Functional Disability Index of the Health Assessment Questionnaire * C-reactive protein or erythrocyte sedimentation rate
Time frame: Week 12
Population: Modified Intention to Treat (mITT) efficacy population included all patients who were randomized and received at least 1 dose of study medication. Patients were analyzed according to the treatment to which they were intended to be randomized. All missing values were imputed as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NP01 | ACR 20 Response Rate at Visit 4 | 108 participants |
| Placebo | ACR 20 Response Rate at Visit 4 | 34 participants |
p-value: 0.00195% CI: [1.39, 3.64]Regression, Logistic
Secondary
Relative Reduction of Morning Stiffness
Data for the duration of morning stiffness were obtained from patient diaries. Duration of morning stiffness was the difference between the time of resolution of morning stiffness and the time of wake-up. Duration of morning stiffness is the average of the morning stiffness duration (minutes) over the last 7 days prior to visit day (including day of visit). If more than 4 assessments were missing, then the duration was set to missing. Baseline was the value recorded at Week -1 (Visit 0).
Time frame: Week 12
Population: Modified Intention to Treat (mITT) efficacy population included all patients who were randomized and received at least 1 dose of study medication. Patients were analyzed according to the treatment to which they were intended to be randomized. Excludes those participants with missing data. Analysis used last observation carried forward imputation.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| NP01 | Relative Reduction of Morning Stiffness | -55.22 Relative Change from Baseline (%) | 95% Confidence Interval 63.583 |
| Placebo | Relative Reduction of Morning Stiffness | -34.62 Relative Change from Baseline (%) | 95% Confidence Interval 67.018 |
p-value: 0.001595% CI: [-31.7, -6.1]Hodges-Lehman method