TL011 in Severe, Active Rheumatoid Arthritis Patients

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: TL011, anti CD20, for the treatment of rheumatoid arthritis; Biological: MabThera infusions

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Plzen, Czechia, 323 00
    • Teva Investigational Site 5428
  • Prague 2, Czechia, 12850
    • Teva Investigational Site 5426
  • Uherske Hradiste, Czechia, 686 01
    • Teva Investigational Site 5429
• Hungary
  • Budapest, Hungary, 1083
    • Teva Investigational Site 5123
  • Budapest, Hungary, H-1023
    • Teva Investigational Site 5122
  • Debrecen, Hungary, 4032
    • Teva Investigational Site 5125
  • Szeged, Hungary, H-6720
    • Teva Investigational Site 5124
• Italy
  • Firenze, Italy, 50139
    • Teva Investigational Site 3077
  • Genova, Italy, 16132
    • Teva Investigational Site 3075
  • Pavia, Italy, 27100
    • Teva Investigational Site 3078
  • Siena, Italy, 53100
    • Teva Investigational Site 3076
• Spain
  • Barakaldo, Spain, 48903
    • Teva Investigational Site 3170
  • Guadalajara, Spain, 19002
    • Teva Investigational Site 3168
  • Madrid, Spain, 28009
    • Teva Investigational Site 3167
  • Sevilla, Spain, 41014
    • Teva Investigational Site 3169
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Teva Investigational Site 3434
  • Staffordshire, United Kingdom, WS11 5XY
    • Teva Investigational Site 3433
  • Wirral, Merseyside, United Kingdom, CH49 5PE
    • Teva Investigational Site 3435

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Teva Pharmaceutical Industries, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2010
• Primary Completion (Actual): April 23, 2012
• Study Completion (Actual): April 23, 2012

Study Registration Dates

• First Submitted: May 11, 2010
• First Submitted That Met QC Criteria: May 13, 2010
• First Posted (Estimate): May 14, 2010

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: RA-TL011-101; 2009-015702-18 (EudraCT Number)