- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02149121
PK Similarity Prospective Phase 3 Study in Patients With Rheumatoid Arthritis (rituximab)
A Randomized, Controlled, Double-Blind, Parallel-Group, Phase 3 Study to Compare the Pharmacokinetics, Efficacy and Safety Between CT-P10, Rituxan and MabThera in Patients With Rheumatoid Arthritis
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient is male or female between 18 and 75 years old, inclusive.
- Patient has a diagnosis of RA according to the revised 1987 ACR classification criteria (Arnett et al 1988) for at least 6 months prior to randomization.
- Patient has active disease as defined by the presence of 6 or more swollen joints (of 66 assessed) and 6 or more tender joints (of 68 assessed), and serum CRP ≥1.5 mg/dL (≥15 mg/L) or an ESR ≥28 mm/hour.
- Patient has experienced an inadequate response to previous or current treatment with the anti-TNF agents infliximab
- Patient has a proper discontinuation period after treatment with interleukin-1 receptor (IL-1R) antagonist, interleukin-6 receptor (IL-6R) antibody, or abatacept.
Exclusion Criteria:
- Patient has taken more than 2 biologic agents.
- Patient has previously been administered Rituximab or participated in a Rituximab biosimilar study.
- Patient has allergies or hypersensitivity to murine, chimeric, human, or humanized proteins.
- Patient has current or past history of chronic infection with hepatitis B, hepatitis C, or infection with human immunodeficiency virus (HIV)-1 or -2 or who has a positive result to the screening test for these infections.
- Patient has an infection requiring oral antibiotics 2 weeks before randomization, parenteral injection of antibiotics 4 weeks before randomization, other serious infection 6 months before randomization, a history of recurrent herpes zoster or other chronic or recurrent infection 6 weeks before randomization.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CT-P10
rituximab, CT-P10(experimental drug), 1000mg by intravenous infusion.
2 infusions with a 2-week interval between the first and second infusion
|
1000mg by intravenous infusion.
2 infusions with a 2-week interval between the first and second infusion
Other Names:
|
Active Comparator: Rituxan
US-licensed referece product, 1000mg by intravenous infusion.
2 infusions with a 2-week interval between the first and second infusions
|
1000mg by intravenous infusion.
2 infusions with a 2-week interval between the first and second infusion
Other Names:
US-licensed reference product, 1000mg by intravenous infusion.
2 infusions with a 2-week interval between the first and second infusion
Other Names:
|
Active Comparator: MabThera
EU-approved reference product, 1000mg by intravenous infusion.
2 infusions with a 2-week interval between the first and second infusions
|
1000mg by intravenous infusion.
2 infusions with a 2-week interval between the first and second infusion
Other Names:
EU-approved reference product, 1000mg by intravenous infusion.
2 infusions with a 2-week interval between the first and second infusion
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Analysis of Serum AUC0-last of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
Time Frame: over the first 24 weeks
|
For evaluation of pharmacokinetics (PK), the primary endpoint was defined as the analysis of serum AUC0-last, AUC0-inf and Cmax of rituximab during the 1st course of the Main Study Period (over the first 24 weeks). During the 1st course of the Main Study Period, blood samples for PK analysis were collected every week from Week 0 to Week 4, every 4 weeks from Week 4 to Week 16, followed by Week 24. AUC0-last: Area under the concentration-time curve from time to the last measurable concentration over both doses of the 1st course |
over the first 24 weeks
|
Analysis of Serum AUC0-inf of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
Time Frame: at Week 24 of the Main Study Period
|
For evaluation of PK, the primary endpoint was defined as the analysis of serum AUC0-last, AUC0-inf and Cmax of rituximab during the 1st course of the Main Study Period (over the first 24 weeks). During the 1st course of the Main Study Period, blood samples for PK analysis were collected every week from Week 0 to Week 4, every 4 weeks from Week 4 to Week 16, followed by Week 24. AUC0-inf: Area under the concentration-time curve from time 0 extrapolated to infinity over both doses of the 1st course |
at Week 24 of the Main Study Period
|
Analysis of Serum Cmax of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
Time Frame: at Week 24 of the Main Study Period
|
For evaluation of pharmacokinetics (PK), the primary endpoint was defined as the analysis of serum AUC0-last, AUC0-inf and Cmax of rituximab during the 1st course of the Main Study Period (over the first 24 weeks). During the 1st course of the Main Study Period, blood samples for PK analysis were collected every week from Week 0 to Week 4, every 4 weeks from Week 4 to Week 16, followed by Week 24. Cmax: Observed maximum concentration after the seocnd infusion of the 1st course |
at Week 24 of the Main Study Period
|
Analysis of Change From Baseline of DAS28 (CRP) at Week 24 (ANCOVA)
Time Frame: at Week 24 of the Main Study Period
|
For evaluation of efficacy, the primary endpoint was defined as the analysis of change from baseline in disease activity measured by disease activity score 28 (DAS 28) C-reactive protein (CRP) at Week 24 between 2 treatment groups, CT-P10 and reference products (combined Rituxan and MabThera) groups.
During the 1st course of the Main Study Period, DAS28 was assessed every 4 weeks from Week 0 to Week 24.
DAS28 (CRP) was calculated using the following formula: DAS28 (CRP) = 0.56 X SQRT(TJC28) + 0.28 X SQRT(SJC28) + 0.36 X ln(CRP+1) + 0.014 X GH on VAS + 0.96.
DAS28 (CRP) provides a number on a scale from 0 to 10 with higher values indicating greater RA disease activity.
|
at Week 24 of the Main Study Period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Descriptive Statistics for Means (SD) for Baseline Value and Change From Baseline in Disease Activity Measured by DAS28 (CRP) of the Main Study Period
Time Frame: at Week 24 of the Main Study Period
|
For evaluation of efficacy, the secondary endpoint was defined as descriptive statistics of mean change from baseline in disease activity measured by DAS 28 (CRP) and DAS28 erythrocyte sedimentation rate (ESR) at Week 24 (efficacy population) and Week 48 (efficacy population - 2nd treatment course in Main Study Period subset) for the Main Study Period between 2 treatment groups, CT-P10 and reference products (combined Rituxan and MabThera) groups.
DAS28 was assessed every 4 weeks from Week 0 to Week 24 during the 1st treatment course of the Main Study Period and every 8 weeks from Week 24 to Week 48 during the 2nd treatment course of the Main Study Period.
DAS28 (CRP) was calculated using the following formula: DAS28 (CRP) = 0.56 X SQRT(TJC28) + 0.28 X SQRT(SJC28) + 0.36 X ln(CRP+1) + 0.014 X GH on VAS + 0.96.
DAS28 (CRP) provides a number on a scale from 0 to 10 with higher values indicating greater RA disease activity.
|
at Week 24 of the Main Study Period
|
Descriptive Statistics for Means (SD) for Baseline Value and Change From Baseline in Disease Activity Measured by DAS28 (CRP) of the Extension Study Period
Time Frame: at Week 24 of the Main Study Period
|
For evaluation of efficacy, the secondary endpoint was defined as descriptive statistics of mean change from baseline in disease activity measured by DAS28 (CRP) and DAS28 (ESR) at Week 72 (efficacy population-Extension Study Period subset) for the Extension Study Period between 4 treatment groups, CT-P10/CT-P10, Rituxan/Rituxan, Rituxan/CT-P10 and MabThera/CT-P10 groups.
DAS28 was assessed every 8 weeks from Week 48 (Week 0 of the Extension Study Period) to Week 72 (Week 24 of the Extension Study Period) during the Extension Study Period.
DAS28 (CRP) was calculated using the following formula: DAS28 (CRP) = 0.56 X SQRT(TJC28) + 0.28 X SQRT(SJC28) + 0.36 X ln(CRP+1) + 0.014 X GH on VAS + 0.96.
DAS28 (CRP) provides a number on a scale from 0 to 10 with higher values indicating greater RA disease activity.
|
at Week 24 of the Main Study Period
|
Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) of the Main Study Period
Time Frame: at Week 24 of the Main Study Period
|
For evaluation of efficacy, the secondary endpoint was defined as descriptive statistics of mean change from baseline in disease activity measured by DAS 28 (CRP) and DAS28 (ESR) at Week 24 (efficacy population) and Week 48 (efficacy population - 2nd treatment course in Main Study Period subset) for the Main Study Period between 2 treatment groups, CT-P10 and reference products (combined Rituxan and MabThera) groups.
DAS28 was assessed every 4 weeks from Week 0 to Week 24 during the 1st treatment course of the Main Study Period and every 8 weeks from Week 24 to Week 48 during the 2nd treatment course of the Main Study Period.
DAS28 (ESR) was calculated using the following formula: DAS28 (CRP) = 0.56 X SQRT(TJC28) + 0.28 X SQRT(SJC28) + 0.36 X ln(ESR) + 0.014 X GH on VAS.
DAS28 (ESR) provides a number on a scale from 0 to 10 with higher values indicating greater RA disease activity.
|
at Week 24 of the Main Study Period
|
Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) of the Extension Study Period
Time Frame: at Week 24 of the Main Study Period
|
For evaluation of efficacy, the secondary endpoint was defined as descriptive statistics of mean change from baseline in disease activity measured by DAS28 (CRP) and DAS28 (ESR) at Week 72 (efficacy population-Extension Study Period subset) for the Extension Study Period between 4 treatment groups, CT-P10/CT-P10, Rituxan/Rituxan, Rituxan/CT-P10 and MabThera/CT-P10 groups.
DAS28 was assessed every 8 weeks from Week 48 (Week 0 of the Extension Study Period) to Week 72 (Week 24 of the Extension Study Period) during the Extension Study Period.
DAS28 (ESR) was calculated using the following formula: DAS28 (CRP) = 0.56 X SQRT(TJC28) + 0.28 X SQRT(SJC28) + 0.36 X ln(ESR) + 0.014 X GH on VAS.
DAS28 (ESR) provides a number on a scale from 0 to 10 with higher values indicating greater RA disease activity.
|
at Week 24 of the Main Study Period
|
Analysis of B-cell Counts at Week 24 of the Main Study Period (ANCOVA)
Time Frame: Week 24
|
For evaluation of pharmacodynamics (PD), the endpoint was defined as B-cell counts at Week 24 between 2 treatment groups, CT-P10 and reference products (combined Rituxan and MabThera) groups.
During the 1st course of the Main Study Period, B-cell kinetics blood samples were collected every week from Week 0 to Week 4, every 4 weeks from Week 4 to Week 16, followed by Week 24.
|
Week 24
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: DaeHyun Yoo, M.D., Ph.D, Hanyang University
Publications and helpful links
General Publications
- Shim SC, Bozic-Majstorovic L, Berrocal Kasay A, El-Khouri EC, Irazoque-Palazuelos F, Cons Molina FF, Medina-Rodriguez FG, Miranda P, Shesternya P, Chavez-Corrales J, Wiland P, Jeka S, Garmish O, Hrycaj P, Fomina N, Park W, Suh CH, Lee SJ, Lee SY, Bae YJ, Yoo DH. Efficacy and safety of switching from rituximab to biosimilar CT-P10 in rheumatoid arthritis: 72-week data from a randomized Phase 3 trial. Rheumatology (Oxford). 2019 Dec 1;58(12):2193-2202. doi: 10.1093/rheumatology/kez152.
- Suh CH, Yoo DH, Berrocal Kasay A, Chalouhi El-Khouri E, Cons Molina FF, Shesternya P, Miranda P, Medina-Rodriguez FG, Wiland P, Jeka S, Chavez-Corrales J, Linde T, Hrycaj P, Abello-Banfi M, Hospodarskyy I, Jaworski J, Piotrowski M, Brzosko M, Krogulec M, Shevchuk S, Calvo A, Andersone D, Park W, Shim SC, Lee SJ, Lee SY. Long-Term Efficacy and Safety of Biosimilar CT-P10 Versus Innovator Rituximab in Rheumatoid Arthritis: 48-Week Results from a Randomized Phase III Trial. BioDrugs. 2019 Feb;33(1):79-91. doi: 10.1007/s40259-018-00331-4.
- Park W, Bozic-Majstorovic L, Milakovic D, Berrocal Kasay A, El-Khouri EC, Irazoque-Palazuelos F, Molina FFC, Shesternya P, Miranda P, Medina-Rodriguez FG, Wiland P, Jeka S, Chavez-Corrales J, Garmish O, Linde T, Rekalov D, Hrycaj P, Krause A, Fomina N, Piura O, Abello-Banfi M, Suh CH, Shim SC, Lee SJ, Lee SY, Kim SH, Yoo DH. Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial. MAbs. 2018 Aug/Sep;10(6):934-943. doi: 10.1080/19420862.2018.1487912. Epub 2018 Jul 16.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- CT-P10 3.2
- 2013-004555-21 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Rheumatoid Arthritis
-
Janssen Research & Development, LLCWithdrawnActive Rheumatoid Arthritis; Rheumatoid Arthritis
-
Centocor, Inc.CompletedRheumatoid Arthritis, Juvenile
-
AmgenTerminated
-
Children's Hospital Medical Center, CincinnatiNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedJuvenile Rheumatoid ArthritisUnited States
-
AmgenImmunex CorporationCompletedJuvenile Rheumatoid Arthritis
-
National Institute of Arthritis and Musculoskeletal...Children's Hospital Medical Center, CincinnatiCompleted
-
University of PittsburghNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedRheumatoid Arthritis | Juvenile Rheumatoid ArthritisUnited States
-
University of Missouri-ColumbiaCompletedJuvenile Rheumatoid ArthritisUnited States
-
Assistance Publique - Hôpitaux de ParisSociete Francaise de RhumatologieRecruiting
-
Amsterdam UMC, location VUmcEuropean CommissionCompletedRheumatoId ArthritisNetherlands, Germany, Portugal, Italy, Hungary, Romania, Slovakia
Clinical Trials on CT-P10
-
CelltrionCompletedFollicular LymphomaKorea, Republic of
-
Yuyu Pharma, Inc.Active, not recruiting
-
University of MichiganNational Institute on Aging (NIA)Completed
-
Minneamrita Therapeutics LLCRecruitingMetastatic Adenocarcinoma of the PancreasKorea, Republic of
-
CelltrionCompleted
-
University of WashingtonNational Cancer Institute (NCI)TerminatedRecurrent Marginal Zone Lymphoma | Waldenstrom Macroglobulinemia | Marginal Zone Lymphoma | Refractory Marginal Zone Lymphoma | Recurrent Waldenstrom Macroglobulinemia | Refractory Waldenstrom MacroglobulinemiaUnited States
-
University of PittsburghTerminatedCarcinoma, Squamous Cell of Head and NeckUnited States
-
CelltrionCompleted
-
Northwell HealthHeartFlow, Inc.CompletedAngina, Stable Chest Pain
-
Northwell HealthToshiba America Medical Systems, Inc.Enrolling by invitationCoronary Artery Disease | Chest Pain | Acute Coronary Syndrome | Acute Myocardial InfarctionUnited States