Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, RA, AZD5672
Brief summary
This study is being carried out to investigate if AZD5672 is effective in treating Rheumatoid Arthritis (RA) and if so how it compares to placebo (a substance which does not have any action) and etanercept (a medicine already available to treat Rheumatoid Arthritis) when added to treatment with methotrexate. The purpose of this study is also to find out which dose of AZD5672 is the most effective at treating RA and to find out how well the body tolerates AZD5672 when taken for up to 12 weeks.
Interventions
DRUGAZD5672
20 mg oral, once daily
DRUGEtanercept
50 mg, subcutaneous injection, weekly
DRUGPlacebo
placebo, oral, once daily
Sponsors
AstraZeneca
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of RA with active disease defined as: ≥4 swollen joints and ≥6 tender/painful joints, and either have (blood tests) elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). * At least one of the following: documented history of positive rheumatoid factor (blood test), current presence of positive rheumatoid factor (blood test), baseline radiographic erosion, presence of serum anti-cyclic citrullinated peptide antibodies (bloo * Be receiving either: Oral (tablets) or subcutaneous (injection) methotrexate for at least 6 months prior to randomisation.
Exclusion criteria
* Any other inflammatory disease in addition to RA that may interfere with the study (e.g. polymyalgia rheumatica, giant cell arteritis, reactive arthritis, etc). * Current chronic pain disorders including fibromyalgia and chronic fatigue syndromes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology 20 Response (ACR20) | 12 weeks | The number of participants with greater to or equal to 20% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology 50 Response (ACR50) | 12 weeks | The number of participants with greater to or equal to 50% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment. |
| American College of Rheumatology 70 Response (ACR70) | 12 weeks | The number of participants with greater to or equal to 70% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment. |
| Disease Activity Score (Based on 28 Joint Count) (DAS28) | Baseline to 12 Weeks | Change from baseline in the DAS28 composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of disease activity; and ESR) after 12 Weeks' treatment. A change of zero indicates no effect of treatment and a negative change of 1.2 indicates a clinically important improvement in symptoms. The DAS scale runs from 0 to 10, with the higher scores indicating worse RA symptoms. |
| Health Assessment Questionnaire - Disability Index (HAQ-DI) | Baseline to 12 Weeks | Change from baseline in HAQ-DI (a measure of patients assessment of physical function scored between zero and 3) after 6 months' treatment, calculated as score at 12 Weeks minus score at baseline. A change of zero indicates no effect of treatment and a negative change of 0.22 or greater indicates an improvement in symptoms. The HAQ-DI scale runs from 0 to 3, with higher scores indicating greater disability. |
Countries
Bulgaria, Colombia, Czechia, Hungary, Italy, Latvia, Malta, Poland, Romania, Russia, Serbia, Slovakia, South Africa, Ukraine
Participant flow
Recruitment details
The first participant enrolled on 01 July 2008, and the last participant completed the study on 08 April 2009. Participants were recruited from 61 centres in 14 countries in Europe, Southern Africa and South America.
Pre-assignment details
Male or female adult patients with active rheumatoid arthritis (on background treatment of methotrexate) were randomly assigned to receive AZD5672 at 20, 50, 100 or 150 mg once daily, placebo or etanercept. It was planned to randomise approx 360 patients in total, 60 to the open-label etanercept arm and 300 in total to the AZD5672 or placebo arms.
Participants by arm
| Arm | Count |
|---|---|
| AZD5672 20 mg AZD5672 20 mg, oral tablets, once daily, double-blinded | 52 |
| AZD5672 50 mg AZD5672 50 mg, oral tablets, once daily, double-blinded | 52 |
| AZD5672 100 mg AZD5672 100 mg, oral tablets, once daily, double-blinded | 51 |
| AZD5672 150 mg AZD5672 150 mg, oral tablets, once daily, double-blinded | 76 |
| Placebo Placebo to AZD5672, oral tablets, once daily, double-blinded | 65 |
| Etanercept Etanercept 50 mg, subcutaneous injection, once weekly, open-label | 75 |
| Total | 371 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 | 7 | 7 | 3 | 5 |
| Overall Study | AZ decision - Hepatitis C ab reactive | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Hepatotoxicity - not an AE | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Incorrect enrollment | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 3 | 2 | 3 | 1 |
Baseline characteristics
| Characteristic | AZD5672 20 mg | AZD5672 50 mg | AZD5672 100 mg | AZD5672 150 mg | Placebo | Etanercept | Total |
|---|---|---|---|---|---|---|---|
| Age Continuous | 53 Year STANDARD_DEVIATION 12.7 | 53 Year STANDARD_DEVIATION 12 | 54 Year STANDARD_DEVIATION 10.8 | 53 Year STANDARD_DEVIATION 10.2 | 53 Year STANDARD_DEVIATION 10.6 | 54 Year STANDARD_DEVIATION 9.6 | 53 Year STANDARD_DEVIATION 10.8 |
| Disease Activity Score (based on 28 joint counts) (DAS28) | 6.6 Units on a scale STANDARD_DEVIATION 0.8 | 6.5 Units on a scale STANDARD_DEVIATION 0.87 | 6.4 Units on a scale STANDARD_DEVIATION 0.72 | 6.3 Units on a scale STANDARD_DEVIATION 0.79 | 6.6 Units on a scale STANDARD_DEVIATION 0.74 | 6.7 Units on a scale STANDARD_DEVIATION 0.8 | 6.5 Units on a scale STANDARD_DEVIATION 0.79 |
| Duration of rheumatoid arthritis Duration of rheumatoid arthritis <= 5years | 29 participants | 22 participants | 26 participants | 37 participants | 29 participants | 27 participants | 170 participants |
| Duration of rheumatoid arthritis Duration of rheumatoid arthritis > 5 years | 23 participants | 30 participants | 25 participants | 39 participants | 36 participants | 48 participants | 201 participants |
| Sex: Female, Male Female | 45 Participants | 45 Participants | 45 Participants | 67 Participants | 54 Participants | 66 Participants | 322 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 6 Participants | 9 Participants | 11 Participants | 9 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 52 | 11 / 52 | 15 / 51 | 21 / 76 | 15 / 65 | 16 / 75 |
| serious Total, serious adverse events | 0 / 52 | 1 / 52 | 2 / 51 | 2 / 76 | 1 / 65 | 0 / 75 |
Outcome results
Primary
American College of Rheumatology 20 Response (ACR20)
The number of participants with greater to or equal to 20% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD5672 20 mg | American College of Rheumatology 20 Response (ACR20) | 20 Participants |
| AZD5672 50 mg | American College of Rheumatology 20 Response (ACR20) | 15 Participants |
| AZD5672 100 mg | American College of Rheumatology 20 Response (ACR20) | 17 Participants |
| AZD5672 150 mg | American College of Rheumatology 20 Response (ACR20) | 34 Participants |
| Placebo | American College of Rheumatology 20 Response (ACR20) | 25 Participants |
| Etanercept | American College of Rheumatology 20 Response (ACR20) | 58 Participants |
Secondary
American College of Rheumatology 50 Response (ACR50)
The number of participants with greater to or equal to 50% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD5672 20 mg | American College of Rheumatology 50 Response (ACR50) | 10 Participants |
| AZD5672 50 mg | American College of Rheumatology 50 Response (ACR50) | 5 Participants |
| AZD5672 100 mg | American College of Rheumatology 50 Response (ACR50) | 6 Participants |
| AZD5672 150 mg | American College of Rheumatology 50 Response (ACR50) | 11 Participants |
| Placebo | American College of Rheumatology 50 Response (ACR50) | 6 Participants |
| Etanercept | American College of Rheumatology 50 Response (ACR50) | 35 Participants |
Secondary
American College of Rheumatology 70 Response (ACR70)
The number of participants with greater to or equal to 70% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD5672 20 mg | American College of Rheumatology 70 Response (ACR70) | 3 Participants |
| AZD5672 50 mg | American College of Rheumatology 70 Response (ACR70) | 2 Participants |
| AZD5672 100 mg | American College of Rheumatology 70 Response (ACR70) | 3 Participants |
| AZD5672 150 mg | American College of Rheumatology 70 Response (ACR70) | 2 Participants |
| Placebo | American College of Rheumatology 70 Response (ACR70) | 3 Participants |
| Etanercept | American College of Rheumatology 70 Response (ACR70) | 12 Participants |
Secondary
Disease Activity Score (Based on 28 Joint Count) (DAS28)
Change from baseline in the DAS28 composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of disease activity; and ESR) after 12 Weeks' treatment. A change of zero indicates no effect of treatment and a negative change of 1.2 indicates a clinically important improvement in symptoms. The DAS scale runs from 0 to 10, with the higher scores indicating worse RA symptoms.
Time frame: Baseline to 12 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD5672 20 mg | Disease Activity Score (Based on 28 Joint Count) (DAS28) | -1.3 Units on a scale | Standard Deviation 1.27 |
| AZD5672 50 mg | Disease Activity Score (Based on 28 Joint Count) (DAS28) | -1.1 Units on a scale | Standard Deviation 1.01 |
| AZD5672 100 mg | Disease Activity Score (Based on 28 Joint Count) (DAS28) | -1.3 Units on a scale | Standard Deviation 1.23 |
| AZD5672 150 mg | Disease Activity Score (Based on 28 Joint Count) (DAS28) | -1.3 Units on a scale | Standard Deviation 1.15 |
| Placebo | Disease Activity Score (Based on 28 Joint Count) (DAS28) | -1.1 Units on a scale | Standard Deviation 1.13 |
| Etanercept | Disease Activity Score (Based on 28 Joint Count) (DAS28) | -2.6 Units on a scale | Standard Deviation 1.35 |
Secondary
Health Assessment Questionnaire - Disability Index (HAQ-DI)
Change from baseline in HAQ-DI (a measure of patients assessment of physical function scored between zero and 3) after 6 months' treatment, calculated as score at 12 Weeks minus score at baseline. A change of zero indicates no effect of treatment and a negative change of 0.22 or greater indicates an improvement in symptoms. The HAQ-DI scale runs from 0 to 3, with higher scores indicating greater disability.
Time frame: Baseline to 12 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD5672 20 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) | -0.3 Units on a scale | Standard Deviation 0.47 |
| AZD5672 50 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) | -0.2 Units on a scale | Standard Deviation 0.48 |
| AZD5672 100 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) | -0.2 Units on a scale | Standard Deviation 0.4 |
| AZD5672 150 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) | -0.3 Units on a scale | Standard Deviation 0.33 |
| Placebo | Health Assessment Questionnaire - Disability Index (HAQ-DI) | -0.3 Units on a scale | Standard Deviation 0.47 |
| Etanercept | Health Assessment Questionnaire - Disability Index (HAQ-DI) | -0.5 Units on a scale | Standard Deviation 0.49 |