Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
Brief summary
The purpose of this study is to confirm that AZD9056 is effective in treating rheumatoid arthritis with regard to signs and symptoms and to determine what dose is favourable over a 6-month treatment period. Patients will receive background treatment with either Methotrexate or Sulphasalazine
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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 and current presence of positive rheumatoid factor (blood test), baseline radiographic erosion. Be receiving either oral (tablets) or subcutaneous/intramuscular (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, e t c). Current chronic pain disorders including fibromyalgia and chronic fatigue syndromes. Persistently abnormal liver function enzymes (blood test).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology 20 Response (ACR20) at 6 Months | 6 months | 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 6 months' treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology 50 Response (ACR50) at 6 Months | 6 months | 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 6 months' treatment. |
| American College of Rheumatology 70 Response (ACR70) at 6 Months | 6 months | 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 6 months' treatment |
| Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months. | Baseline to 6 months | 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 6 months' 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) at 6 Months. | Baseline to 6 months | 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 6 months 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
Argentina, Australia, Belgium, Canada, Czechia, France, Mexico, Poland, Romania, Russia, Slovakia, United States
Participant flow
Recruitment details
The first participant enrolled on 01 August 2007, the last participant completed the study on 08 April 2009. Participants were recruited from 59 centres in 12 countries in Australia, Canada, Europe, Russia, South America, and the USA.
Pre-assignment details
Male/female participants with active rheumatoid arthritis (and on background methotrexate or sulphasalazine) were randomly assigned to receive AZD9056 at 50, 100, 200 or 400 mg once daily, placebo or etanercept. It was planned to randomise approximately 360 participants, 60 to the open-label etanercept arm and 300 to the AZD9056 or placebo arms
Participants by arm
| Arm | Count |
|---|---|
| AZD9056 50 mg AZD9056 50 mg, oral tablets, once daily, double blinded | 63 |
| AZD9056 100 mg AZD9056 100 mg, oral tablets, once daily, double blinded | 64 |
| AZD9056 200 mg AZD9056 200 mg, oral tablets, once daily, double blinded | 63 |
| AZD9056 400 mg AZD9056 400 mg, oral tablets, once daily, double blinded | 64 |
| Placebo Placebo to AZD9056, oral tablets, once daily, double blinded | 65 |
| Etanercept Etanercept 50 mg, subcutaneous injection, once weekly, open label | 64 |
| Total | 383 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 3 | 6 | 9 | 7 | 2 |
| Overall Study | Did not receive Treatment | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Incorrect enrollment | 1 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 1 | 2 | 1 | 0 |
| Overall Study | Long break in taking Medication | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Oral corticotherapy for acute urticaria | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 9 | 5 | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | AZD9056 50 mg | AZD9056 100 mg | AZD9056 200 mg | AZD9056 400 mg | Placebo | Etanercept | Total |
|---|---|---|---|---|---|---|---|
| Age Continuous | 52 Years STANDARD_DEVIATION 12.8 | 54 Years STANDARD_DEVIATION 11.5 | 50 Years STANDARD_DEVIATION 11.9 | 52 Years STANDARD_DEVIATION 11.8 | 51 Years STANDARD_DEVIATION 11.9 | 51 Years STANDARD_DEVIATION 10.8 | 51.7 Years STANDARD_DEVIATION 11.76 |
| Sex: Female, Male Female | 56 Participants | 54 Participants | 51 Participants | 59 Participants | 54 Participants | 55 Participants | 329 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 12 Participants | 5 Participants | 11 Participants | 9 Participants | 54 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 | 17 / 63 | 24 / 64 | 20 / 63 | 29 / 64 | 20 / 65 | 11 / 64 |
| serious Total, serious adverse events | 2 / 63 | 0 / 64 | 1 / 63 | 1 / 64 | 1 / 65 | 2 / 64 |
Outcome results
Primary
American College of Rheumatology 20 Response (ACR20) at 6 Months
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 6 months' treatment
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD9056 50 mg | American College of Rheumatology 20 Response (ACR20) at 6 Months | 23 Participants |
| AZD9056 100 mg | American College of Rheumatology 20 Response (ACR20) at 6 Months | 26 Participants |
| AZD9056 200 mg | American College of Rheumatology 20 Response (ACR20) at 6 Months | 23 Participants |
| AZD9056 400 mg | American College of Rheumatology 20 Response (ACR20) at 6 Months | 21 Participants |
| Placebo | American College of Rheumatology 20 Response (ACR20) at 6 Months | 21 Participants |
| Etanercept | American College of Rheumatology 20 Response (ACR20) at 6 Months | 42 Participants |
Secondary
American College of Rheumatology 50 Response (ACR50) at 6 Months
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 6 months' treatment.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD9056 50 mg | American College of Rheumatology 50 Response (ACR50) at 6 Months | 13 Participants |
| AZD9056 100 mg | American College of Rheumatology 50 Response (ACR50) at 6 Months | 8 Participants |
| AZD9056 200 mg | American College of Rheumatology 50 Response (ACR50) at 6 Months | 9 Participants |
| AZD9056 400 mg | American College of Rheumatology 50 Response (ACR50) at 6 Months | 13 Participants |
| Placebo | American College of Rheumatology 50 Response (ACR50) at 6 Months | 11 Participants |
| Etanercept | American College of Rheumatology 50 Response (ACR50) at 6 Months | 30 Participants |
Secondary
American College of Rheumatology 70 Response (ACR70) at 6 Months
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 6 months' treatment
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD9056 50 mg | American College of Rheumatology 70 Response (ACR70) at 6 Months | 6 Participants |
| AZD9056 100 mg | American College of Rheumatology 70 Response (ACR70) at 6 Months | 7 Participants |
| AZD9056 200 mg | American College of Rheumatology 70 Response (ACR70) at 6 Months | 5 Participants |
| AZD9056 400 mg | American College of Rheumatology 70 Response (ACR70) at 6 Months | 5 Participants |
| Placebo | American College of Rheumatology 70 Response (ACR70) at 6 Months | 3 Participants |
| Etanercept | American College of Rheumatology 70 Response (ACR70) at 6 Months | 15 Participants |
Secondary
Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months.
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 6 months' 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 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9056 50 mg | Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months. | -1.2 Composite score | Standard Deviation 1.27 |
| AZD9056 100 mg | Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months. | -1.4 Composite score | Standard Deviation 1.63 |
| AZD9056 200 mg | Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months. | -1.1 Composite score | Standard Deviation 1.47 |
| AZD9056 400 mg | Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months. | -1.4 Composite score | Standard Deviation 1.37 |
| Placebo | Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months. | -1 Composite score | Standard Deviation 1.24 |
| Etanercept | Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months. | -2.3 Composite score | Standard Deviation 1.38 |
Secondary
Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 Months.
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 6 months 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 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9056 50 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 Months. | -0.3 Composite score | Standard Deviation 0.57 |
| AZD9056 100 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 Months. | -0.3 Composite score | Standard Deviation 0.51 |
| AZD9056 200 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 Months. | -0.2 Composite score | Standard Deviation 0.5 |
| AZD9056 400 mg | Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 Months. | -0.3 Composite score | Standard Deviation 0.55 |
| Placebo | Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 Months. | -0.3 Composite score | Standard Deviation 0.46 |
| Etanercept | Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 Months. | -0.6 Composite score | Standard Deviation 0.66 |