search
Back to results

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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GP2013
MabThera
Rituxan
Sponsored by
Sandoz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Miller Clinical Research
  • Bluegrass Community Research, Inc.
  • Klein & Associates
  • Klein & Associates
  • Clinical Pharmacology Study Group
  • Physician Research Collaboration, LLC
  • Innovative Health Research
  • DJL Clinical Research PLLC
  • Health Research of Oklahoma
  • Altoona Center for Clinical Research
  • Clinical Research Center of Reading LLC
  • Low Country Rheumatology, PA
  • Regional Health Clinical Research
  • West Tennessee Research Institute
  • Arthritis & Osteoporosis Center of South Texas
  • The Seattle Arthritis Center
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative site
  • Investigative site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative site
  • North Estonia Medical Centre Foundation
  • Investigative Site
  • Investigative site
  • Investigative Site
  • Investigative site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Pest Megyei Flór Ferenc
  • Megyei Csolnoky Ferenc Kórház Nonprofit Zrt.
  • Investigative site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative site
  • Investigative site
  • Investigative site
  • Investigative Site
  • Investigative Site
  • Investigative site
  • Investigative Site
  • Investigative Site
  • Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

GP2013

MabThera

Rituxan

Arm Description

Outcomes

Primary Outcome Measures

AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA
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

Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA
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
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
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
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
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)
Summary of Disease Activity According to SDAI
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))
Participant Response as Assessed by EULAR Response Criteria
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).

Full Information

First Posted
January 10, 2011
Last Updated
January 23, 2018
Sponsor
Sandoz
Collaborators
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT01274182
Brief Title
GP2013 in the Treatment of RA Patients Refractory to or Intolerant of Standard Therapy
Official Title
A Randomized, Double-blind, Controlled Study to Evaluate PK, PD, Safety and Efficacy of GP2013 and Rituximab in Patients With Rheumatoid Arthritis Refractory or Intolerant to Standard DMARDs and up to Three Anti-TNF Therapies.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sandoz
Collaborators
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
312 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GP2013
Arm Type
Experimental
Arm Title
MabThera
Arm Type
Active Comparator
Arm Title
Rituxan
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
GP2013
Intervention Description
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
Intervention Type
Biological
Intervention Name(s)
MabThera
Other Intervention Name(s)
EU-Rituximab
Intervention Description
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
Intervention Type
Biological
Intervention Name(s)
Rituxan
Other Intervention Name(s)
US-Rituximab
Intervention Description
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
Primary Outcome Measure Information:
Title
AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA
Description
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
Time Frame
From baseline to 24 weeks
Secondary Outcome Measure Information:
Title
Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA
Description
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.
Time Frame
From baseline to week 24
Title
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
Description
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
Time Frame
14 days
Title
Change From Baseline in DAS28(CRP) at Week 24
Description
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.
Time Frame
24 weeks
Title
Number of Patients With ACR20 (CRP) Response
Description
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)
Time Frame
24 weeks
Title
Summary of Disease Activity According to CDAI
Description
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)
Time Frame
At week 24
Title
Summary of Disease Activity According to SDAI
Description
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))
Time Frame
At week 24
Title
Participant Response as Assessed by EULAR Response Criteria
Description
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).
Time Frame
At week 24
Other Pre-specified Outcome Measures:
Title
Number of Patients With at Least One Anti-Drug-Antibody (ADA) Positive Serum Sample
Description
Number of patients with at least one post-baseline Anti-Drug-Antibody (ADA) positive serum sample until the last study visit. Sampling was at Day 1, 29, 113, 169, 267, 365, optional visit 1 (could be at any time between day 169 - week 24 and day 365 - week 52 for patients, who received a 2nd treatment course) and optional visit 2 (only applicable for patients, who received a 2nd treatment course, 26 weeks thereafter, if this was after day 365 - week 52).
Time Frame
through study completion, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandoz Biopharmaceuticals
Organizational Affiliation
Sandoz
Official's Role
Study Director
Facility Information:
Facility Name
Miller Clinical Research
City
Los Angeles
State/Province
California
ZIP/Postal Code
90057
Country
United States
Facility Name
Bluegrass Community Research, Inc.
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40504
Country
United States
Facility Name
Klein & Associates
City
Cumberland
State/Province
Maryland
ZIP/Postal Code
21502
Country
United States
Facility Name
Klein & Associates
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Clinical Pharmacology Study Group
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
Physician Research Collaboration, LLC
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68516
Country
United States
Facility Name
Innovative Health Research
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
DJL Clinical Research PLLC
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
Health Research of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Clinical Research Center of Reading LLC
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Low Country Rheumatology, PA
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Regional Health Clinical Research
City
Rapid City
State/Province
South Dakota
Country
United States
Facility Name
West Tennessee Research Institute
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
Facility Name
Arthritis & Osteoporosis Center of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78232
Country
United States
Facility Name
The Seattle Arthritis Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98133
Country
United States
Facility Name
Investigative Site
City
Buenos Aires#1
Country
Argentina
Facility Name
Investigative Site
City
Buenos Aires#2
Country
Argentina
Facility Name
Investigative Site
City
Innsbruck
Country
Austria
Facility Name
Investigative Site
City
Vienna#1
Country
Austria
Facility Name
Investigative site
City
Kortrijk
Country
Belgium
Facility Name
Investigative site
City
Merksem
Country
Belgium
Facility Name
Investigative Site
City
Curitiba
Country
Brazil
Facility Name
Investigative Site
City
Goiânia
Country
Brazil
Facility Name
Investigative Site
City
Sao Paulo#1
Country
Brazil
Facility Name
Investigative site
City
Sao Paulo#2
Country
Brazil
Facility Name
North Estonia Medical Centre Foundation
City
Tallinn
Country
Estonia
Facility Name
Investigative Site
City
Amiens Cedex
Country
France
Facility Name
Investigative site
City
Cahors
Country
France
Facility Name
Investigative Site
City
Corbeil Essonnes
Country
France
Facility Name
Investigative site
City
La Gaillarde
Country
France
Facility Name
Investigative Site
City
Orleans
Country
France
Facility Name
Investigative Site
City
Frankfurt
Country
Germany
Facility Name
Investigative Site
City
Freiburg
Country
Germany
Facility Name
Investigative Site
City
Göttingen
Country
Germany
Facility Name
Investigative Site
City
Hildesheim
Country
Germany
Facility Name
Investigative Site
City
Jena
Country
Germany
Facility Name
Investigative Site
City
München
Country
Germany
Facility Name
Investigative Site
City
Nürnberg
Country
Germany
Facility Name
Investigative Site
City
Ratingen
Country
Germany
Facility Name
Investigative Site
City
Regensburg
Country
Germany
Facility Name
Investigative Site
City
Würzburg
Country
Germany
Facility Name
Pest Megyei Flór Ferenc
City
Kistarcsa
ZIP/Postal Code
2143
Country
Hungary
Facility Name
Megyei Csolnoky Ferenc Kórház Nonprofit Zrt.
City
Veszprem
ZIP/Postal Code
H-2800
Country
Hungary
Facility Name
Investigative site
City
Ajmer
Country
India
Facility Name
Investigative Site
City
Bangalore
Country
India
Facility Name
Investigative Site
City
Hyderabad
Country
India
Facility Name
Investigative Site
City
Jaipur
Country
India
Facility Name
Investigative Site
City
New Delhi
Country
India
Facility Name
Investigative Site
City
Secunderabad
Country
India
Facility Name
Investigative Site
City
Milano
Country
Italy
Facility Name
Investigative site
City
Bucharest#1
Country
Romania
Facility Name
Investigative site
City
Bucharest#2
Country
Romania
Facility Name
Investigative site
City
Cluj
Country
Romania
Facility Name
Investigative Site
City
Madrid
Country
Spain
Facility Name
Investigative Site
City
Mérida
Country
Spain
Facility Name
Investigative site
City
Santiago de Compostela
Country
Spain
Facility Name
Investigative Site
City
Sevilla
Country
Spain
Facility Name
Investigative Site
City
Istanbul
Country
Turkey
Facility Name
Investigative Site
City
Izmir
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
28637670
Citation
Smolen JS, Cohen SB, Tony HP, Scheinberg M, Kivitz A, Balanescu A, Gomez-Reino J, Cen L, Zhu P, Shisha T. A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis. Ann Rheum Dis. 2017 Sep;76(9):1598-1602. doi: 10.1136/annrheumdis-2017-211281. Epub 2017 Jun 21.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs