GP2013 in the Treatment of RA Patients Refractory to or Intolerant of Standard Therapy
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| ClinicalTrials.gov Identifier: NCT01274182 |
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Recruitment Status :
Completed
First Posted : January 11, 2011
Results First Posted : January 24, 2018
Last Update Posted : January 24, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rheumatoid Arthritis | Biological: GP2013 Biological: MabThera Biological: Rituxan | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 312 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 Start Date : | January 2011 |
| Actual Primary Completion Date : | January 2016 |
| Actual Study Completion Date : | November 2016 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: GP2013 |
Biological: GP2013
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15) |
| Active Comparator: MabThera |
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 |
| Active Comparator: Rituxan |
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 |
- 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
- 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).
- 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).
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01274182
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| Study Director: | Sandoz Biopharmaceuticals | Sandoz |
| Responsible Party: | Sandoz |
| ClinicalTrials.gov Identifier: | NCT01274182 |
| Other Study ID Numbers: |
GP13-201 2010-021184-32 ( EudraCT Number ) GPN013A2301 ( Other Identifier: Novartis ) |
| First Posted: | January 11, 2011 Key Record Dates |
| Results First Posted: | January 24, 2018 |
| Last Update Posted: | January 24, 2018 |
| Last Verified: | January 2018 |
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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases |
Immune System Diseases Rituximab Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |