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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004555-21 | EudraCT Number |
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This is a Phase 3 Study to Compare the Pharmacokinetics, Efficacy and Safety between CT-P10, Rituxan and MabThera in Patients with Rheumatoid Arthritis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CT-P10 | Experimental | rituximab, CT-P10(experimental drug), 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion |
|
| Rituxan | Active Comparator | US-licensed referece product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusions |
|
| MabThera | Active Comparator | EU-approved reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusions |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CT-P10 | Biological | 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion |
|
| 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) | 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) | 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) | 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) |
| 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 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| DaeHyun Yoo, M.D., Ph.D | Hanyang University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31184752 | Derived | 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. | |
| 30719632 |
| Label | URL |
|---|---|
| Related Info | View source |
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A total of 495 participants were screened for the study. Of theses, 111 participants were excluded from the study due to screening failure and 384 participants were enrolled in the study. Of these 384 participants, 12 participants from the significantly GCP noncompliant study center were excluded from all analysis populations.
Participants recruited from 76 study centers (including 1 GCP noncompliant study center) in Europe, Asia Pacific, and Latin America.
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| ID | Title | Description |
|---|---|---|
| FG000 | CT-P10 (Main Study Period) | This group received 1000mg rituximab (CT-P10; experimental drug) by intravenous (IV) infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, Methotrexate (MTX) (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| FG001 | Rituxan (Main Study Period) | This group received 1000mg rituximab (Rituxan; US-licensed reference product) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| FG002 | MabThera (Main Study Period) | This group received 1000mg rituximab (MabThera; EU-approved reference product) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| FG003 | CT-P10/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive CT-P10 with their first infusion in the Main Study Period, were considered as CT-P10/CT-P10 group and maintained CT-P10 for the treatment course of the Extension Study Period at Extension Week 0. This group received 1000mg rituximab (CT-P10; experimental drug) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course in the Extension Study Period followed by 1000mg rituximab (CT-P10; experimental drug) infusions in the Main Study Period. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| FG004 | Rituxan/Rituxan (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive Rituxan with their first infusion in the Main Study Period, were randomized in a 1:1 ratio to Rituxan/Rituxan group and Rituxan/CT-P10 group at Extension Week 0. This group is for participants who were assigned as Rituxan/Rituxan group and received 1000mg rituximab (Rituxan; US-licensed reference product) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course in the Extension Study Period followed by 1000mg rituximab (Rituxan; US-licensed reference product) infusions in the Main Study Period. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| FG005 | Rituxan/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive Rituxan with their first infusion in the Main Study Period, were randomized in a 1:1 ratio to Rituxan/Rituxan group and Rituxan/CT-P10 group at Extension Week 0. This group is for participants who were assigned as Rituxan/CT-P10 group and received 1000mg rituximab (CT-P10; experimental drug) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course in the Extension Study Period followed by 1000mg rituximab (Rituxan; US-licensed reference product) infusions in the Main Study Period. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| FG006 | MabThera/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive MabThera with their first infusion in the Main Study Period, were considered as MabThera/CT-P10 group and received CT-P10 for the treatment course of the Extension Study Period at Extension Week 0. This group received 1000mg rituximab (CT-P10; experimental drug) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course in the Extension Study Period followed by 1000mg rituximab (Rituxan; US-licensed reference product) infusions in the Main Study Period. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Main Study Period |
|
| ||||||||||||||||||
| Extension Study Period |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | CT-P10 (Main Study Period) | This group received 1000mg rituximab (CT-P10; experimental drug) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Study is divided in 2 period (Main Study Period and Extension Study Period) and baseline measures were separately entered. Therefore, a row population differs from the Overall. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Analysis of Serum AUC0-last of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA) | 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 | PK population - The PK analysis set for the Main Study Period consisted of all patients who received 2 full doses (Week 0 and Week 2) of the study drug and provided at least 1 post-treatment PK concentration result during the 1st course in the Main Study Period. | Posted | Geometric Least Squares Mean | Standard Error | h*μg/mL | over the first 24 weeks |
|
Serious adverse events (SAEs) and adverse events (AEs) were assessed from the date the informed consent form was signed until the participant's last visit, up to week 24 of extension period (up to week 72).
At each level of summarization, a participant is counted only once if they reported one or more events. Only the most severe event is counted. SAEs and AEs are considered to have occurred in the Main Study Period if start date is before the first infusion of the Extension Study Period or if participant did not enter the Extension Study Period, and considered to have occurred in the Extension Study Period if the start date is on or after the date of first infusion of the Extension Study Period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CT-P10 (Main Study Period) | This group received 1000mg rituximab (CT-P10; experimental drug) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| SungYoung Lee | Celltrion, Inc. | +82 32 850 6532 | SungYoung.Lee@celltrion.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 1, 2016 | Aug 19, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 2, 2017 | Aug 19, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| C000626854 | CT-P10 |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
| Rituxan | Drug | US-licensed reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion |
|
|
| MabThera | Drug | EU-approved reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion |
|
|
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 |
| 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 | 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 | 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 | 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) | 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 |
| Derived |
| 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. |
| 30010481 | Derived | 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. |
| Withdrawal by Subject |
|
| Adverse Event |
|
| Protocol Violation |
|
| Lost to Follow-up |
|
| Death |
|
| Physician Decision |
|
| Developed any malignancy |
|
| Unmet predefined eligibility criteria |
|
| Disease progression |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG001 | Rituxan (Main Study Period) | This group received 1000mg rituximab (Rituxan; US-licensed reference product) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| BG002 | MabThera (Main Study Period) | This group received 1000mg rituximab (MabThera; EU-approved reference product) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| BG003 | CT-P10/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive CT-P10 with their first infusion in the Main Study Period, were considered as CT-P10/CT-P10 group and maintained CT-P10 for the treatment course of the Extension Study Period at Extension Week 0. This group received 1000mg rituximab (CT-P10; experimental drug) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course in the Extension Study Period followed by 1000mg rituximab (CT-P10; experimental drug) infusions in the Main Study Period. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| BG004 | Rituxan/Rituxan (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive Rituxan with their first infusion in the Main Study Period, were randomized in a 1:1 ratio to Rituxan/Rituxan group and Rituxan/CT-P10 group at Extension Week 0. This group is for participants who were assigned as Rituxan/Rituxan group and received 1000mg rituximab (Rituxan; US-licensed reference product) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course in the Extension Study Period followed by 1000mg rituximab (Rituxan; US-licensed reference product) infusions in the Main Study Period. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| BG005 | Rituxan/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive Rituxan with their first infusion in the Main Study Period, were randomized in a 1:1 ratio to Rituxan/Rituxan group and Rituxan/CT-P10 group at Extension Week 0. This group is for participants who were assigned as Rituxan/CT-P10 group and received 1000mg rituximab (CT-P10; experimental drug) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course in the Extension Study Period followed by 1000mg rituximab (Rituxan; US-licensed reference product) infusions in the Main Study Period. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| BG006 | MabThera/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive MabThera with their first infusion in the Main Study Period, were considered as MabThera/CT-P10 group and received CT-P10 for the treatment course of the Extension Study Period at Extension Week 0. This group received 1000mg rituximab (CT-P10; experimental drug) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course in the Extension Study Period followed by 1000mg rituximab (Rituxan; US-licensed reference product) infusions in the Main Study Period. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| BG007 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Age, Categorical | Study is divided in 2 period (Main Study Period and Extension Study Period) and baseline measures were separately entered. Therefore, a row population differs from the Overall | Count of Participants | Participants |
|
| Age, Continuous | Study is divided in 2 period (Main Study Period and Extension Study Period) and baseline measures were separately entered. Therefore, a row population differs from the Overall | Median | Full Range | years |
|
| Age, Continuous | Study is divided in 2 period (Main Study Period and Extension Study Period) and baseline measures were separately entered. Therefore, a row population differs from the Overall | Median | Full Range | years |
|
| Sex: Female, Male | Study is divided in 2 period (Main Study Period and Extension Study Period) and baseline measures were separately entered. Therefore, a row population differs from the Overall | Count of Participants | Participants |
|
| Sex: Female, Male | Study is divided in 2 period (Main Study Period and Extension Study Period) and baseline measures were separately entered. Therefore, a row population differs from the Overall | Count of Participants | Participants |
|
| CT-P10 (Main Study Period) |
This group received 1000mg rituximab (CT-P10; experimental drug) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| OG001 | Rituxan (Main Study Period) | This group received 1000mg rituximab (Rituxan; US-licensed reference product) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
| OG002 | MabThera (Main Study Period) | This group received 1000mg rituximab (MabThera; EU-approved reference product) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. |
|
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| Primary | Analysis of Serum AUC0-inf of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA) | 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 | PK population - The PK analysis set for the Main Study Period consisted of all patients who received 2 full doses (Week 0 and Week 2) of the study drug and provided at least 1 post-treatment PK concentration result during the 1st course in the Main Study Period. | Posted | Geometric Least Squares Mean | Standard Error | h*μg/mL | at Week 24 of the Main Study Period |
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| Primary | Analysis of Serum Cmax of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA) | 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 | PK population - The PK analysis set for the Main Study Period consisted of all patients who received 2 full doses (Week 0 and Week 2) of the study drug and provided at least 1 post-treatment PK concentration result during the 1st course in the Main Study Period. | Posted | Geometric Least Squares Mean | Standard Error | ug/mL | at Week 24 of the Main Study Period |
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| Primary | Analysis of Change From Baseline of DAS28 (CRP) at Week 24 (ANCOVA) | 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. | Efficacy population - The efficacy analysis set for the Main Study Period consisted of all who received at least 1 full dose (1000mg) of study drug (CT-P10, Rituxan or MabThera), who had at least 1 post-treatment efficacy result and who did not have any major protocol violation including a violation of the inclusion and exclusion criteria. | Posted | Least Squares Mean | Standard Error | score on a scale | at Week 24 of the Main Study Period |
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| Secondary | Descriptive Statistics for Means (SD) for Baseline Value and Change From Baseline in Disease Activity Measured by DAS28 (CRP) 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. | Weeks 0 and 24 data were analysed by efficacy population who received at least 1 full dose of study drug and provided at least 1 post treatment efficacy result during 1st course. Week 48 data were analysed by 'efficacy-2nd course subset' who received at least 1 full dose and provided at least 1 post treatment efficacy result during 2nd course. | Posted | Mean | Standard Deviation | score on a scale | at Week 24 of the Main Study Period |
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| Secondary | Descriptive Statistics for Means (SD) for Baseline Value and Change From Baseline in Disease Activity Measured by DAS28 (CRP) of the Extension 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. | Efficacy - Extension Study Period subset: The "efficacy - Extension Study Period subset" consisted of all patients in the efficacy population who received at least 1 full dose (1000 mg) of study drug and provided at least 1 post-treatment efficacy result during the Extension Study Period. | Posted | Mean | Standard Deviation | score on a scale | at Week 24 of the Main Study Period |
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| Secondary | Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) 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. | Weeks 0 and 24 data were analysed by efficacy population who received at least 1 full dose of study drug and provided at least 1 post treatment efficacy result during 1st course. Week 48 data were analysed by 'efficacy-2nd course subset' who received at least 1 full dose and provided at least 1 post treatment efficacy result during 2nd course. | Posted | Mean | Standard Deviation | score on a scale | at Week 24 of the Main Study Period |
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| Secondary | Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) of the Extension 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. | Efficacy - Extension Study Period subset: The "efficacy - Extension Study Period subset" consisted of all patients in the efficacy population who received at least 1 full dose (1000 mg) of study drug and provided at least 1 post-treatment efficacy result during the Extension Study Period. | Posted | Mean | Standard Deviation | score on a scale | at Week 24 of the Main Study Period |
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| Secondary | Analysis of B-cell Counts at Week 24 of the Main Study Period (ANCOVA) | 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. | PD population - The PD analysis set for the Main Study Period consisted of all patients who received at least 1 full dose (1000mg) of study drug and provided at least 1 post-treatment PD result during the 1st course in the Main Study Period. | Posted | Geometric Least Squares Mean | Standard Error | cells/mcL | Week 24 |
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| 1 |
| 161 |
| 13 |
| 161 |
| 88 |
| 161 |
| EG001 | Rituxan (Main Study Period) | This group received 1000mg rituximab (Rituxan; US-licensed reference product) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. | 0 | 151 | 14 | 151 | 72 | 151 |
| EG002 | MabThera (Main Study Period) | This group received 1000mg rituximab (MabThera; EU-approved reference product) by IV infusion. Each participant received up to 3 treatment courses (2 treatment courses in the Main Study Period, and 1 additional treatment course in the Extension Study Period), if they met predefined eligibility criteria. Each course consisted of 2 infusions with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. | 0 | 60 | 4 | 60 | 29 | 60 |
| EG003 | CT-P10/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive CT-P10 with their first infusion in the Main Study Period, were considered as CT-P10/CT-P10 group and maintained CT-P10 for the treatment course of the Extension Study Period at Extension Week 0. This group received 1000mg rituximab (CT-P10; experimental drug) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. | 0 | 122 | 4 | 122 | 27 | 122 |
| EG004 | Rituxan/Rituxan (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive Rituxan with their first infusion in the Main Study Period, were randomized in a 1:1 ratio to Rituxan/Rituxan group and Rituxan/CT-P10 group at Extension Week 0. This group received 1000mg rituximab (Rituxan; US-licensed reference product) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. | 0 | 64 | 0 | 64 | 16 | 64 |
| EG005 | Rituxan/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive Rituxan with their first infusion in the Main Study Period, were randomized in a 1:1 ratio to Rituxan/Rituxan group and Rituxan/CT-P10 group at Extension Week 0. This group received 1000mg rituximab (CT-P10) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. | 0 | 62 | 1 | 62 | 17 | 62 |
| EG006 | MabThera/CT-P10 (Extension Study Period) | For the Extension Study Period, participants, who were assigned to receive MabThera with their first infusion in the Main Study Period, were considered as MabThera/CT-P10 group and received CT-P10 for the treatment course of the Extension Study Period at Extension Week 0. This group received 1000mg rituximab (CT-P10) by IV infusion with a 2-week interval between the first and second infusions of a 24-week course. Throughout the study, MTX (7.5-25 mg/week orally or parenterally) and folic acid (≥ 5 mg/week) were coadministered. | 0 | 47 | 0 | 47 | 7 | 47 |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
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| Colitis ischaemic | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Chest pain | General disorders | MedDRA (18.1) | Systematic Assessment | General disorders and administration site conditions |
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| Cholecystitis | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Localised infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Fracture | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Injury | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Hand deformity | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Adenocarcinoma of colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.1) | Systematic Assessment |
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| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.1) | Systematic Assessment |
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| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.1) | Systematic Assessment |
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| Lymphangioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.1) | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
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| Vertebrobasilar insufficiency | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA (18.1) | Systematic Assessment |
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| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Infleunza | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Infusion-related reaction | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
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| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Vaginal infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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Investigators could publish any information whatsoever and/or any discussion relating to Sponsor, Confidential Information, Inventions or work performed by investigator for Sponsor with the prior written consent of Sponsor.
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Between 18 and 65 years |
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| >=65 years |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Male |
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| Primary PK analysis were analyzed using an ANCOVA model with treatment group as a fixed effect and gender, region, race, prior anti TNF alpha blocker status, and RF or anti-CCP status fitted as covariates. | Ratio of geometric least squares means | 89.89 | 2-Sided | 90 | 81.85 | 98.72 | Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means. | Equivalence | The equivalence of PK was to be concluded if the 90% CI for the ratio of geometric means in AUC0-last, AUC0-inf, and Cmax was entirely contained within the PK equivalence bounds of 80% and 125% for the following comparisons: CT-P10 versus Rituxan, CT-P10 versus MabThera, and Rituxan versus MabThera. |
| Primary PK analysis were analyzed using an ANCOVA model with treatment group as a fixed effect and gender, region, race, prior anti TNF alpha blocker status, and RF or anti-CCP status fitted as covariates. | Ratio of geometric least squares means | 106.58 | 2-Sided | 90 | 97.03 | 117.08 | Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means. | Equivalence | The equivalence of PK was to be concluded if the 90% CI for the ratio of geometric means in AUC0-last, AUC0-inf, and Cmax was entirely contained within the PK equivalence bounds of 80% and 125% for the following comparisons: CT-P10 versus Rituxan, CT-P10 versus MabThera, and Rituxan versus MabThera. |
| Primary PK analysis were analyzed using an ANCOVA model with treatment group as a fixed effect and gender, region, race, prior anti TNF alpha blocker status, and RF or anti-CCP status fitted as covariates. | Ratio of geometric least squares means | 89.00 | 2-Sided | 90 | 84.01 | 94.28 | Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means. | Equivalence | The equivalence of PK was to be concluded if the 90% CI for the ratio of geometric means in AUC0-last, AUC0-inf, and Cmax was entirely contained within the PK equivalence bounds of 80% and 125% for the following comparisons: CT-P10 versus Rituxan, CT-P10 versus MabThera, and Rituxan versus MabThera. |
| Primary PK analysis were analyzed using an ANCOVA model with treatment group as a fixed effect and gender, region, race, prior anti TNF alpha blocker status, and RF or anti-CCP status fitted as covariates. | Ratio of geometric least squares means | 106.66 | 2-Sided | 90 | 100.56 | 113.13 | Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means. | Equivalence | The equivalence of PK was to be concluded if the 90% CI for the ratio of geometric means in AUC0-last, AUC0-inf, and Cmax was entirely contained within the PK equivalence bounds of 80% and 125% for the following comparisons: CT-P10 versus Rituxan, CT-P10 versus MabThera, and Rituxan versus MabThera. |
Therapeutic equivalence was to be concluded if the 90% CI for the treatment difference in the change from baseline of DAS28 (CRP) at Week 24 was entirely within the equivalence margin of ±0.50. |
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| Week 24 (1st course Week 24) |
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| Week 48 (2nd course Week 24) |
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| Week 24 (1st course Week 24) |
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| Week 48 (2nd course Week 24) |
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