GP2013 in the Treatment of RA Patients Refractory to or Intolerant of Standard Therapy

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Biological: MabThera; Biological: GP2013; Biological: Rituxan

• Registration Number: NCT01274182
• Lead Sponsor: Sandoz

Brief Summary

The purpose of this study is to determine the PK/PD, efficacy and safety of GP2013 in patients with severe rheumatoid arthritis.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-01-10
• Study First Submitted QC: 2011-01-10
• Study First Posted: 2011-01-11
• Primary Completion: 2016-01
• Study Completion: 2016-11
• Disposition First Submitted: 2016-12-14
• Disposition First Submitted QC: 2016-12-14
• Disposition First Posted: 2016-12-15
• Results First Submitted: 2017-11-09
• Status Verified: 2018-01
• Results First Submitted QC: 2018-01-23
• Last Update Submitted: 2018-01-23
• Results First Posted: 2018-01-24
• Last Update Posted: 2018-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 312

Inclusion Criteria

• Rheumatoid arthritis as defined by the 1987 ACR classification
• Severe active seropositive disease
• Inadequate response or intolerance to other DMARDs and anti-TNFs
• Treatment with Methotrexate

Exclusion Criteria

• Patients with systemic manifestations of rheumatoid arthritis
• Female patients nursing
• Women of childbearing potential unless using birth control
• Active infection
• Known immunodeficiency syndrome
• Positive Hepatitis B surface antigen or antibodies to Hepatitis C
• History of cancer

Other protocol-defined inclusion/exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MabThera	MabThera	-
GP2013	GP2013	-
Rituxan	Rituxan	-

Primary Outcome Measures

Name	Time	Method
AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA	From baseline to 24 weeks	Area under the curve AUC(0-inf) calculated based on serum samples, collected from baseline up to 24 weeks: Day 1, 4, 8, 15, 18, 29, 57, 85,113 and 169

Secondary Outcome Measures

Name	Time	Method
Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA	From baseline to week 24	Maximum serum concentration (Cmax) after the first infusion of GP2013, MabThera and Rituxan in patients with RA. Samples collected from baseline up to 24 weeks: Day 1, 4, 8, 15, 18, 29, 57, 85,113 and 169.
Area Under the Effect Curve From Baseline to Day 14 (AUEC(0-14d)) of Percent B-cells of GP2013, MabThera and Rituxan in Patients With RA	14 days	Area under the effect curve of percent change of peripheral B-cell count from baseline to Day 14 (AUEC(0-14d)) of GP2013, MabThera and Rituxan in patients with RA
Change From Baseline in DAS28(CRP) at Week 24	24 weeks	Change from baseline in Disease Activity Score 28 joint count - C-reactive proteine DAS28(CRP) at Week 24.; In order to calculate the DAS28(CRP) the number of tender joints and swollen joints were assessed using 28-joint count (tender28 and swollen28).The patient's global assessment of disease activity (GH) measured on a Visual Analogue Scale (VAS from 0mm - best to 100mm - worst) was obtained.; DAS28(CRP) = 0.56 \* sqrt(tender28) + 0.28\* sqrt(swollen28) + 0.36 \* ln(CRP+1) + 0.014 \* GH + 0.96 The DAS28(CRP) provides a number on a scale from 0 to 10 indicating the current activity of the RA, while lower values correspond with less disease activity. A decrease in DAS28 signifies a clinical improvement.
Number of Patients With ACR20 (CRP) Response	24 weeks	A patient will be considered as improved according the ACR20 criteria; * at least 20 % improvement from baseline in tender joint count, using the 68-joint count; * at least 20 % improvement from baseline in swollen joint count, using the 66-joint count; * and at least 20% improvement from baseline in a least 3 of the following 5 measures: * Patient's assessment of RA pain (VAS 100 mm); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire disability index); * Acute phase reactant (C-reactive protein or erythrocyte sedimentation rate)
Summary of Disease Activity According to CDAI	At week 24	In order to calculate the Clinical Disease Activity Index (CDAI) the number of tender and swollen joints were assessed using the 28 -joint count (tender28 and swollen28). The patient's global assessment of disease activity and the physician's global assessment of disease activity were measured using a Visual Analogue Scale (VAS) of 10 cm (from 0=best to 10=worst).; CDAI = tender28 + swollen28 + patient's global assessment (in cm) + physician's global assessment (in cm)
Participant Response as Assessed by EULAR Response Criteria	At week 24	Present DAS28 ≤ 3.2 (low): good response (if improvement \> 1.2), moderate response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6).; Present DAS28 \> 3.2 to ≤ 5.1 (moderate): moderate response (if improvement \> 1.2), moderate response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6).; Present DAS28 \> 5.1 (high): moderate response (if improvement \> 1.2), no response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6).
Summary of Disease Activity According to SDAI	At week 24	In order to calculate the Simplified Disease Activity Index (SDAI) the number of tender and swollen joints were assessed using the 28 -joint count (tender28 and swollen28). The patient's global assessment of disease activity and the physician's global assessment of disease activity were measured using a Visual Analogue Scale (VAS) of 10 cm (from 0=best to 10=worst).; SDAI = CDAI + CRP (in mg/dL); (CDAI = tender28 + swollen28 + patient's global assessment (in cm) + physician's global assessment (in cm))

Trial Locations

Locations (20)

Clinical Pharmacology Study Group; 🇺🇸 Worcester, Massachusetts, United States

Physician Research Collaboration, LLC; 🇺🇸 Lincoln, Nebraska, United States

Bluegrass Community Research, Inc.; 🇺🇸 Lexington, Kentucky, United States

Miller Clinical Research; 🇺🇸 Los Angeles, California, United States

Klein & Associates; 🇺🇸 Hagerstown, Maryland, United States

DJL Clinical Research PLLC; 🇺🇸 Charlotte, North Carolina, United States

Health Research of Oklahoma; 🇺🇸 Oklahoma City, Oklahoma, United States

Altoona Center for Clinical Research; 🇺🇸 Duncansville, Pennsylvania, United States

Clinical Research Center of Reading LLC; 🇺🇸 Wyomissing, Pennsylvania, United States

Arthritis & Osteoporosis Center of South Texas; 🇺🇸 San Antonio, Texas, United States

Investigative Site; 🇹🇷 Izmir, Turkey

The Seattle Arthritis Center; 🇺🇸 Seattle, Washington, United States

Investigative site; 🇪🇸 Santiago de Compostela, Spain

Megyei Csolnoky Ferenc Kórház Nonprofit Zrt.; 🇭🇺 Veszprem, Hungary

North Estonia Medical Centre Foundation; 🇪🇪 Tallinn, Estonia

Pest Megyei Flór Ferenc; 🇭🇺 Kistarcsa, Hungary

Low Country Rheumatology, PA; 🇺🇸 Charleston, South Carolina, United States

West Tennessee Research Institute; 🇺🇸 Jackson, Tennessee, United States

Innovative Health Research; 🇺🇸 Las Vegas, Nevada, United States

Regional Health Clinical Research; 🇺🇸 Rapid City, South Dakota, United States