Rheumatoid Arthritis
Conditions
Keywords
Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) Degrader
Brief summary
This study aims to evaluate the efficacy of BGB-45035 in adults with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).
Interventions
DRUGBGB-45035
Administered orally
DRUGPlacebo
Administered orally
Sponsors
BeiGene
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
* Diagnosed with rheumatoid arthritis (RA) based on American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for at least 3 months prior to screening * Demonstrated an inadequate response to, or loss of response or intolerance to at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) (Hydroxychloroquine, methotrexate \[MTX\], leflunomide, or sulfasalazine) or 1 biologic disease-modifying antirheumatic drug (bDMARD)/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) treatment * Must be on stable dose of one of the following permitted therapies for ≥ 4 weeks prior to screening and during the study: methotrexate between 7.5 mg to 25 mg/week, hydroxychloroquine up to 400 mg/day, leflunomide up to 20 mg/day, or sulfasalazine between 1000 mg/day to 3000 mg/day
Exclusion criteria
* Class IV RA based on American College of Rheumatology revised criteria for classification of functional status in rheumatoid arthritis * Patients with a history of cancer in the last 5 years before the Screening Visit, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin * Have failed more than 2 b/tsDMARDs (eg, excluded if have failed 2 bDMARDs and 1 tsDMARD)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Disease Activity Score - C-reactive protein (DAS28-CRP) at Week 12 | Baseline and Week 12 | The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), high-sensitivity C-reactive protein (hsCRP in mg/L), and Patient's Global Assessment of Arthritis Pain (measured on a Visual Analog Scale \[VAS\] from 0 \[no pain\] to 100 \[worst possible pain\]). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A score greater than 5.1 indicates high disease activity, a score between 3.2 and 5.1 indicates moderate disease activity, a score between 2.6 and 3.2 indicates low disease activity, and a score less than 2.6 indicates the participant is in remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with a 20% improvement in American College of Rheumatology Criteria (ACR20) | Baseline and Week 12 | The ACR20 is defined as at least 20% improvement in the ACR core set values as defined below. Participants must meet 3 conditions for improvement from Baseline: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP). |
| Percentage of participants with a 50% improvement in American College of Rheumatology Criteria (ACR50) | Baseline and Week 12 | The ACR50 is defined as at least 50% improvement in the ACR core set values as defined below. Participants must meet 3 conditions for improvement from Baseline: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP). |
| Percentage of participants with a 70% improvement in American College of Rheumatology Criteria (ACR70) | Baseline and Week 12 | The ACR70 is defined as at least 70% improvement in the ACR core set values as defined below. Participants must meet 3 conditions for improvement from Baseline: 1. ≥ 70% improvement in 68-tender joint count; 2. ≥ 70% improvement in 66-swollen joint count; and 3. ≥ 70% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP). |
| Change from Baseline in Tender Joint Count 68 (TJC 68) | Baseline up to Week 12 | The TJC 68 is an assessment of tenderness or pain in 68 joints. Sixty-eight joints will be assessed for tenderness/pain by an independent, blinded assessor. The response to pressure/motion on each joint is assessed using the following scale: Present/Absent/Not Done/Not Applicable. A lower score indicates there is less pain or tenderness present, while a higher score indicates more pain or tenderness is present. |
| Change from baseline in Swollen Joint Count 66 (SJC 66) | Baseline up to Week 12 | The SJC 66 is an assessment of swelling in 66 joints. Sixty-six joints will be assessed for swelling by an independent, blinded assessor. The swelling present in each joint is assessed using the following scale: Present/Absent/Not Done/Not Applicable. A lower score indicates there is less swelling present, while a higher score indicates more swelling is present. |
| Change from baseline in physician's global assessment of disease activity (PhGADA_VAS) | Baseline up to Week 12 | The PhGADA\_VAS is a single item that asks the physician to assess the participant's current disease activity on a 0- to 100-mm visual analog scale (VAS), with anchors of 0 = "no disease activity" and 100 = "extremely active disease." |
| Change from baseline in Simplified Disease Activity Index (SDAI) score | Baseline up to Week 12 | The simplified disease activity index (SDAI) is a composite measure that sums the total number of: * 28 tender joint counts, * 28 swollen joint counts, * Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 where 0= lowest disease activity and 10 = highest; * Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10, where 0 = lowest disease activity and 10 = highest, and * C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to approximately 86 where lower scores indicate less disease activity. |
| Change from baseline in Clinical Disease Activity Index (CDAI) score | Baseline up to Week 12 | The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 where 0 = lowest disease activity and 10 = highest; * Physician's Global Assessment of Disease Activity (measured on a VAS from 0 to 10 where 0 = lowest disease activity and 10 = highest). The CDAI score ranges from 0 to 76 where lower scores indicate less disease activity. |
| Change from baseline of participant's global assessment of disease activity (PaGADA_VAS) | Baseline up to Week 12 | The PaGADA\_VAS is a single item that asks the patient to rate the current severity of their disease activity on a 0- to 100-mm VAS, with anchors of 0 = "no disease activity" and 100 = "extremely active disease." |
| Change from baseline of Participant's global assessment of arthritis pain (VAS) | Baseline up to Week 12 | The Participants's global assessment of arthritis pain (VAS) is a single item that asks the patient to rate the current severity of their pain in relation to their RA on a 0- to 100-mm VAS, with anchors of "no pain" and "worst possible pain." |
| Change from baseline of Participant's assessment of physical function as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) | Baseline up to Week 12 | The HAQ-DI is a patient-reported questionnaire that is commonly used in RA to measure disease-associated disability (assessment of physical function). Participants answer 24 questions using a scale from 0 to 3 to score difficulty when performing daily activities over the past week (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Scores on each task are averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three represents very severe, high-dependency disability. |
| Number of participants with adverse events (AEs) | Up to approximately 4 months | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including findings from laboratory tests |
Countries
China
Contacts
STUDY_DIRECTORStudy Director
BeiGene
Outcome results
None listed