Arthritis, Rheumatoid
Conditions
Brief summary
Researchers are looking for new ways to treat rheumatoid arthritis (RA). Methotrexate (MTX) is a standard (usual) treatment for RA. However, MTX and other current treatments may not work well to treat RA symptoms for many people. This study will help find out if a study medicine called tulisokibart can treat symptoms of active RA in people who are taking MTX. In this study, researchers will look at different doses of tulisokibart. Researchers want to learn if at least one of the study doses of tulisokibart works better than a placebo to lessen RA symptoms. A placebo looks like the study medicine but has no study medicine in it. Using a placebo helps researchers better understand the effects of the study medicine.
Detailed description
This study consists of a 12-week Placebo-controlled Period and a 116-week Long-term Extension (LTE), which is composed of a 44-week Main Extension and an 72-week Optional Extension
Interventions
DRUGTulisokibart
Subcutaneous (SC) administration
DRUGPlacebo
SC Injection
DRUGMethotrexate
Background Therapy - SC injection or oral administration. Per protocol, parenteral administration is allowed.
Sponsors
Merck Sharp & Dohme LLC
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 80 Years
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has a clinical diagnosis of rheumatoid arthritis (RA) and fulfillment of 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria * Has active disease defined as ≥6 tender joints (based on 68 joints) and ≥6 swollen joints (based on 66 joints) * Has current treatment with oral or parenteral methotrexate (MTX) therapy * Has history of one of the following: a) biologic disease-modifying antirheumatic drug (bDMARD) naïve, or b) bDMARD-Inadequate Response (IR)/intolerant up to a maximum of 2 classes of bDMARDS
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving American College of Rheumatology 20% Response Criteria (ACR20) at Week 12 | Week 12 | The ACR20 response is a composite measure to evaluate disease activity in RA. ACR20 response is defined as a ≥20% improvement in: a) swollen joint count (66 joints) and tender joint count (68 joints) (0= Absent; 1= Present) and b) ≥20% improvement in ≥3 of the following 5 assessments and questionnaires: i) Health Assessment Questionnaire Disability Index (HAQ-DI) (0=without any difficulty; 3= unable to do) a higher score=worse disability, ii) Physician Global Assessment of Disease Activity (PGA) (0= not active to 10= very active) a higher score= more active disease; iii) Patient's Global Assessment of Disease Activity (PtGA) (0= not active to 10= very active) a higher score= more active disease; iv) Patient assessment of Pain Severity (0= no pain to 10= most severe pain) a higher score = more pain; v) High-sensitivity C-reactive protein (hsCRP) serum values, a lower value indicates less inflammation. The proportion of participants with ACR20 response at Week 12 will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50) at Week 12 | Week 12 | The ACR50 response is a composite measure to evaluate disease activity in RA. ACR50 response is defined as a ≥50% improvement in: a) swollen joint count (66 joints) and tender joint count (68 joints) (0= Absent; 1= Present) and b) ≥50% improvement in ≥3 of the following 5 assessments and questionnaires: i) Health Assessment Questionnaire Disability Index (HAQ-DI) (0= without any difficulty; 3= unable to do) a higher score=worse disability, ii) Physician Global Assessment of Disease Activity (PGA) (0= not active to 10= very active) a higher score= more active disease; iii) Patient's Global Assessment of Disease Activity (PtGA) (0= not active to 10= very active) a higher score= more active disease; iv) Patient assessment of Pain Severity (0= no pain to 10= most severe pain) a higher score = more pain; v) High-sensitivity C-reactive protein (hsCRP) serum values, a lower value indicates less inflammation. The proportion of participants with ACR50 response at Week 12 will be presented. |
| Proportion of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70) at Week 12 | Week 12 | The ACR70 response is a composite measure to evaluate disease activity in RA. ACR70 response is defined as a ≥70% improvement in: a) swollen joint count (66 joints) and tender joint count (68 joints) (0= Absent; 1= Present) and b) ≥70% improvement in ≥3 of the following 5 assessments and questionnaires: i) Health Assessment Questionnaire Disability Index (HAQ-DI) (0= without any difficulty; 3= unable to do) a higher score=worse disability, ii) Physician Global Assessment of Disease Activity (PGA) (0= not active to 10= very active) a higher score= more active disease; iii) Patient's Global Assessment of Disease Activity (PtGA) (0= not active to 10= very active) a higher score= more active disease; iv) Patient assessment of Pain Severity (0= no pain to 10= most severe pain) a higher score = more pain; v) High-sensitivity C-reactive protein (hsCRP) serum values, a lower value indicates less inflammation. The proportion of participants with ACR70 response at Week 12 will be presented. |
| Proportion of Participants Achieving Low Disease Activity (LDA) based on Disease Activity Score 28 Using C-Reactive Protein (DAS28-CRP) | Week 12 | The DAS28-CRP is a composite measure of RA disease activity. DAS28-CRP is based upon a statistically-derived index combining the following 4 components: i) tender joint count (TJC) (28 joints; 0=absent, 1=present; TJC28), ii) swollen joint count (SJC) (28 joints; 0=absent, 1=present; SJC28), iii) serum high-sensitivity C-reactive protein (hsCRP), serum value decrease indicates less inflammation, and iv) Patient's Global Assessment of Disease Activity (PtGA) (0= not active to 10= very active) a higher score= more active disease. The index is defined as follows: DAS28-CRP = 0.56 × SQRT(TJC28) + 0.28 × SQRT(SJC28) + 0.36 × ln (hsCRP+1) + 0.014 × ptGA+ 0.96. The DAS28-CRP is a scale ranging from 0 to 10 with higher values indicating greater RA disease activity. Remission is indicated by a DAS28-CRP score of \<2.6 and low disease activity (LDA) by a DAS28-CRP score of ≤3.2. The proportion of participants who achieve LDA will be presented. |
| Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12 | Baseline and Week 12 | The HAQ-DI is a 20-item questionnaire that measures physical function in participants with RA. The questionnaire assesses the degree of difficulty a person has in accomplishing tasks in 8 functional area domains (dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area domain are scored from 0 to 3 (0= without any difficulty; 3= unable to do), with a higher score indicating inability to perform activity. The overall disability score (HAQ-DI) is a summation of the highest score from each domain divided by the number of domains completed and ranges from 0 to 3, with the higher value indicating worse disability. The change from baseline to week 12 in the HAQ-DI score will be presented. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately Week 142 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of Participants Who Discontinue Study Intervention Due to an AE | Up to approximately Week 128 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study intervention due to an AE will be reported. |
Countries
Canada, Chile, China, Colombia, Germany, Japan, Poland, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed