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

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ClinicalTrials.gov Identifier: NCT01274182
Recruitment Status : Completed
First Posted : January 11, 2011
Results First Posted : January 24, 2018
Last Update Posted : January 24, 2018
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Sandoz

January 10, 2011
January 11, 2011
November 9, 2017
January 24, 2018
January 24, 2018
January 2011
January 2016   (Final data collection date for primary outcome measure)
AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA [ Time Frame: 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
Compare pharmacokinetics (PK) of GP2013 and rituximab following IV infusion in patients with RA [ Time Frame: 24 weeks ]
Complete list of historical versions of study NCT01274182 on ClinicalTrials.gov Archive Site
  • Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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)
  • Summary of Disease Activity According to SDAI [ Time Frame: 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))
  • Participant Response as Assessed by EULAR Response Criteria [ Time Frame: 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).
  • Additional pharmacokinetic (PK) parameters, pharmacodynamic (PD) and efficacy of GP2013 and rituximab in subjects with RA [ Time Frame: 1.5 years ]
  • Safety and tolerability of GP2013 and rituximab in patients with RA [ Time Frame: 1.5 years ]
Number of Patients With at Least One Anti-Drug-Antibody (ADA) Positive Serum Sample [ Time Frame: through study completion, an average of 1 year ]
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).
Not Provided
 
GP2013 in the Treatment of RA Patients Refractory to or Intolerant of Standard Therapy
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.
The purpose of this study is to determine the PK/PD, efficacy and safety of GP2013 in patients with severe rheumatoid arthritis.
Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Rheumatoid Arthritis
  • Biological: GP2013
    1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
  • Biological: MabThera
    1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
    Other Name: EU-Rituximab
  • Biological: Rituxan
    1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
    Other Name: US-Rituximab
  • Experimental: GP2013
    Intervention: Biological: GP2013
  • Active Comparator: MabThera
    Intervention: Biological: MabThera
  • Active Comparator: Rituxan
    Intervention: Biological: Rituxan
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
312
164
November 2016
January 2016   (Final data collection date for primary outcome measure)

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

Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Austria,   Belgium,   Brazil,   Estonia,   France,   Germany,   Hungary,   India,   Italy,   Romania,   Spain,   Turkey,   United States
 
 
NCT01274182
GP13-201
2010-021184-32 ( EudraCT Number )
GPN013A2301 ( Other Identifier: Novartis )
Yes
Not Provided
Not Provided
Sandoz
Sandoz
Novartis Pharmaceuticals
Study Director: Sandoz Biopharmaceuticals Sandoz
Sandoz
January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP