TL011 in Severe, Active Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and pharmacology of TL011 in patients with severe rheumatoid arthritis.

Official Title
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A Phase Ib Study Evaluating Safety, Pharmacokinetic and Pharmacodynamic Profiles of a Single Course of TL011 Infusions in Subjects With Severe, Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: TL011, anti CD20, for the treatment of rheumatoid arthritis
* Biological: MabThera infusions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects Rheumatoid arthritis as defined by the 1987 ACR Classification Severe active seropositive disease Inadequate response or intolerance to other DMARDs Treatment with MTX Exclusion Criteria: Rheumatic autoimmune disease other than RA Active infection Known immunodeficiency syndrome Positive Hepatitis B surface antigen or antibodies to Hepatitis C History of cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TL011<br>TL011 infusions | Biological: TL011, anti CD20, for the treatment of rheumatoid arthritis<br>* TL011 administered by 2 infusions, 2 weeks apart<br>|
| Active Comparator: MabThera<br>MabThera infusions | Biological: MabThera infusions<br>* MabThera, administered by 2 infusions, 2 weeks apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration Versus Time Curve [AUC(0-t)] in Part B |  | Day 1 to Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) in Part B |  | Day 1 to Day 57 | 
| Number of Participants With Adverse Events in Part B | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | From randomization up to Week 24 | 
| Cmax Post First Dose (C1max) and Post Second Dose (C2max) in Part B |  | Day 1, Day 15 | 
| AUC At First Dose (AUC1) and AUC At Second Dose (AUC2) in Part B |  | Day 1, Day 15 | 
| Percent Change From Baseline in CD19+ B-cell Count in Part B |  | Baseline to Day 57 | 
| Number of Participants With American College of Rheumatology (ACR20) Criteria Response in Part B | Defined as at least 20% improvement from the screening values in swollen and tender joint count and in 3 of the following 5 disease activity measures. Physician's global assessment of disease activity (VAS) Patient's assessment of RA pain (VAS) Patient's global assessment of disease activity Patient's assessment of physical function (Health Assessment Questionnaire) Acute phase reactant (C-reactive protein [CRP]) | Baseline to Day 57 | 
| Area Under the Plasma Concentration Versus Time Curve [AUC (0-t)] for Part A Cohort 2 | Data available for cohort 2 only per planned analysis. | Day 1 to Day 57 | 
| Number of Participants With Adverse Events in Part A | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | From randomization up to Week 24 |