Dual objectives of increased efficacy compared to currently available SoC RA drugs and maintaining a favourable benefit - risk relationship.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
460
Change From Baseline (BL) in Disease Activity Score (DAS)28-C Reactive Protein (CRP) at Week 12
DAS28 is a measure based on assessment of 28 joints for tenderness and swelling (tender and swollen joint counts). Disease Activity Score 28-C reactive protein (DAS28-CRP) is derived using differential weighting given to 4 components: tender joint count (range: 0-28), swollen joint count (range: 0-28), patient global assessment (recorded on a visual analog scale \[VAS\] scale of 0-100 mm), and CRP (milligram per liter). DAS28-CRP score ranges from 0 to 9.4. The lower the DAS28-CRP score is, the better the participant has response (remission = score\<2.6, low disease activity = score≤3.2). A negative value in change from BL indicates an improvement. Mixed Model Repeated Measures was used for statistical analysis, which used the change from BL of DAS28-CRP as an outcome and treatment, scheduled study visit, BL value of DAS28-CRP, treatment by visit interaction and BL by visit interaction as fixed effects. The model used the unstructured covariance matrix.
Time frame: BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12
DAS28-CRP Remission (<2.6) Rates at Week 24
DAS28-CRP is derived using differential weighting given to 4 components: tender joint count, swollen joint count, patient global assessment, and CRP. Remission is defined as DAS28-CRP score \<2.6. Remission rate = the number of responders (who had remission) / (number of responders + non-responders + non-responder assigned by non-responder imputation \[NRI\] after removal of missingness due to COVID-19 and missing components at a given visit)
Time frame: Week 24
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs), and Withdrawals Due to TEAEs
An adverse event (AE) was any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.
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,,UMHAT - Georgi Stranski" EAD
Pleven, Bulgaria
Medical Diagnostic Laboratory Rusev EOOD
Plovdiv, Bulgaria
MHAT Plovdiv AD
Plovdiv, Bulgaria
DCC Sveti Georgi EOOD
Plovdiv, Bulgaria
Independent Medical Diagnostic Laboratory Mediscan EOOD
Plovdiv, Bulgaria
"Medical Center-Teodora" EOOD
Rousse, Bulgaria
UMHAT "Kanev" AD
Rousse, Bulgaria
Medical Center "Spectar" OOD
Sofia, Bulgaria
MHAT "Lyulin" EAD
Sofia, Bulgaria
"DCC 17 - Sofia" EOOD
Sofia, Bulgaria
...and 134 more locations
Time frame: From first dose of study intervention (Day 1) to Week 28
Number of Participants With Clinical Laboratory Abnormalities (Hematology and Chemistry, Without Regard to Baseline Abnormality)
Clinical laboratory abnormality was determined at the investigator's discretion.
Time frame: From BL to Week 28
Number of Participants With Change From Baseline in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria
Abnormality in change from BL in vital signs included: sitting/semi-supine diastolic blood pressure (BP) increase and decrease from BL of \>=20mmHg, systolic BP increase and decrease from BL of \>=30mmHg
Time frame: From BL to Week 28
Number of Participants With Adverse Events of Special Interest
These AEs included severe and opportunistic infection AEs; herpes virus infection AEs; clinically significant categorical increases in hepatic enzymes AST, and ALT and total bilirubin, and potential cases meeting Hy's Law criteria for increased risk of drug induced liver injury (DILI); major adverse cardiovascular events, including pulmonary embolism and deep vein thrombosis, cerebrovascular accident; AEs for decreased renal function, acute kidney injury, clinically significant increases in serum creatinine (Scr) and decreases in estimated glomerular filtration rate (eGFR). Only participants with AEs mentioned above were reported in the table below.
Time frame: From first dose of study intervention (Day 1) to Week 28
Change From Baseline in DAS28-CRP at Week 24
DAS28 is a measure based on assessment of 28 joints for tenderness and swelling (tender and swollen joint counts). DAS28-CRP is derived using differential weighting given to 4 components: tender joint count (range: 0-28), swollen joint count (range: 0-28), patient global assessment (recorded on a visual analog scale \[VAS\] scale of 0-100 mm), and CRP (milligram per liter). DAS28-CRP score ranges from 0 to 9.4. The lower the DAS28-CRP score is, the better the participant has response (remission = score\<2.6, low disease activity = score≤3.2). A negative value in change from BL indicates an improvement.
Time frame: BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 24
American College of Rheumatology (ACR)20, ACR 50, ACR 70, and ACR 90 Responder Rates at Week 12 and Week 24
The American College of Rheumatology's definition for calculating improvement in rheumatoid arthritis (ACR20) is calculated as a \>=20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and CRP. Similarly, ACR50, ACR70, and ACR 90 were calculated with the respective percent improvement. Responder rate = number of responders (who had ACR20/50/70/90 response)/(number of responders + non-responders + non-responder assigned by non-responder imputation \[NRI\] after removal of missingness due to COVID-19 and missing components at a given visit)
Time frame: BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24
Change From Baseline in the Tender/Painful and Swollen Joint Count at Week 12 and Week 24
The endpoint included Tender/Painful Joint Count 68 (TJC68) and 28 (TJC28). TJC68 was assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful in upper body and upper/lower extremity. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). The 28-joints set is the subset of 68 joints set including the following joints: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees. TJC28 was calculated by Pfizer from TJC68. Higher scores indicate higher level of disability.
Time frame: BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24
Change From Baseline in the Physician's Global Assessment (PhGA) of Arthritis at Week 12 and Week 24
PhGA of Arthritis is an evaluation done by investigator based on the participant's disease signs, functional capacity and physical examination, and should be independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS. Physician's Global Assessment score ranges from 0 to 100. Higher scores indicate higher level of disability. A negative value in change from BL indicates an improvement.
Time frame: BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24