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

Rheumatoid Arthritis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01274182
• Other study ID #: GP13-201
• Secondary ID: 2010-021184-32GP
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 10, 2011
• Last updated: January 23, 2018
• Start date: January 2011
• Est. completion date: November 2016

Study information

• Verified date: January 2018
• Source: Sandoz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: November 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• GP2013
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
• MabThera
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
• Rituxan
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)

Locations

Country	Name	City	State
Argentina	Investigative Site	Buenos Aires#1
Argentina	Investigative Site	Buenos Aires#2
Austria	Investigative Site	Innsbruck
Austria	Investigative Site	Vienna#1
Belgium	Investigative site	Kortrijk
Belgium	Investigative site	Merksem
Brazil	Investigative Site	Curitiba
Brazil	Investigative Site	Goiânia
Brazil	Investigative Site	Sao Paulo#1
Brazil	Investigative site	Sao Paulo#2
Estonia	North Estonia Medical Centre Foundation	Tallinn
France	Investigative Site	Amiens Cedex
France	Investigative site	Cahors
France	Investigative Site	Corbeil Essonnes
France	Investigative site	La Gaillarde
France	Investigative Site	Orleans
Germany	Investigative Site	Frankfurt
Germany	Investigative Site	Freiburg
Germany	Investigative Site	Göttingen
Germany	Investigative Site	Hildesheim
Germany	Investigative Site	Jena
Germany	Investigative Site	München
Germany	Investigative Site	Nürnberg
Germany	Investigative Site	Ratingen
Germany	Investigative Site	Regensburg
Germany	Investigative Site	Würzburg
Hungary	Pest Megyei Flór Ferenc	Kistarcsa
Hungary	Megyei Csolnoky Ferenc Kórház Nonprofit Zrt.	Veszprem
India	Investigative site	Ajmer
India	Investigative Site	Bangalore
India	Investigative Site	Hyderabad
India	Investigative Site	Jaipur
India	Investigative Site	New Delhi
India	Investigative Site	Secunderabad
Italy	Investigative Site	Milano
Romania	Investigative site	Bucharest#1
Romania	Investigative site	Bucharest#2
Romania	Investigative site	Cluj
Spain	Investigative Site	Madrid
Spain	Investigative Site	Mérida
Spain	Investigative site	Santiago de Compostela
Spain	Investigative Site	Sevilla
Turkey	Investigative Site	Istanbul
Turkey	Investigative Site	Izmir
United States	Low Country Rheumatology, PA	Charleston	South Carolina
United States	DJL Clinical Research PLLC	Charlotte	North Carolina
United States	Klein & Associates	Cumberland	Maryland
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Klein & Associates	Hagerstown	Maryland
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Innovative Health Research	Las Vegas	Nevada
United States	Bluegrass Community Research, Inc.	Lexington	Kentucky
United States	Physician Research Collaboration, LLC	Lincoln	Nebraska
United States	Miller Clinical Research	Los Angeles	California
United States	Health Research of Oklahoma	Oklahoma City	Oklahoma
United States	Regional Health Clinical Research	Rapid City	South Dakota
United States	Arthritis & Osteoporosis Center of South Texas	San Antonio	Texas
United States	The Seattle Arthritis Center	Seattle	Washington
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts
United States	Clinical Research Center of Reading LLC	Wyomissing	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Sandoz	Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Estonia,  France,  Germany,  Hungary,  India,  Italy,  Romania,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Patients With at Least One Anti-Drug-Antibody (ADA) Positive Serum Sample	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).	through study completion, an average of 1 year
Primary	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	From baseline to 24 weeks
Secondary	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.	From baseline to week 24
Secondary	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	14 days
Secondary	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.	24 weeks
Secondary	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)	24 weeks
Secondary	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)	At week 24
Secondary	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))	At week 24
Secondary	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).	At week 24