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CompletedNCT02149121rituximabUpdated Dec 16, 2021Results posted

PK Similarity Prospective Phase 3 Study in Patients With Rheumatoid Arthritis

A Phase 3 interventional study of CT-P10 and Rituxan in Rheumatoid Arthritis, sponsored by Celltrion. Completed. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-12-16.

Sponsored by Celltrion · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
384
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This is a Phase 3 Study to Compare the Pharmacokinetics, Efficacy and Safety between CT-P10, Rituxan and MabThera in Patients with Rheumatoid Arthritis.

02

Conditions studied

  • Rheumatoid Arthritis
03

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 384 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Celltrion is the lead sponsor of 76 studies on the registry; 3 are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 13 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patient is male or female between 18 and 75 years old, inclusive.
  2. 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.
  3. 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.
  4. Patient has experienced an inadequate response to previous or current treatment with the anti-TNF agents infliximab
  5. 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

Exclusion Criteria:

  1. Patient has taken more than 2 biologic agents.
  2. Patient has previously been administered Rituximab or participated in a Rituximab biosimilar study.
  3. Patient has allergies or hypersensitivity to murine, chimeric, human, or humanized proteins.
  4. 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.
  5. 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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
384 participants (actual)

Study arms

  • 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

    Biological: CT-P10

  • Active comparator
    Rituxan

    US-licensed referece product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusions

    Biological: CT-P10 · Drug: Rituxan

  • Active comparator
    MabThera

    EU-approved reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusions

    Biological: CT-P10 · Drug: MabThera

Interventions

  • BiologicalCT-P10

    1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion

    Also known as: rituximab

  • DrugRituxan

    US-licensed reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion

    Also known as: rituximab

  • DrugMabThera

    EU-approved reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion

    Also known as: rituximab

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: over the first 24 weeks

  2. 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

    Time frame: at Week 24 of the Main Study Period

  3. 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

    Time frame: at Week 24 of the Main Study Period

  4. 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.

    Time frame: at Week 24 of the Main Study Period

Secondary outcomes

  1. 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.

    Time frame: at Week 24 of the Main Study Period

  2. 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.

    Time frame: at Week 24 of the Main Study Period

  3. 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.

    Time frame: at Week 24 of the Main Study Period

  4. 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.

    Time frame: at Week 24 of the Main Study Period

  5. 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.

    Time frame: Week 24

07

Results

Posted Dec 16, 2021

Participant flow

Participants recruited from 76 study centers (including 1 GCP noncompliant study center) in Europe, Asia Pacific, and Latin America.

Main Study Period
Participant flow — Main Study Period
MilestoneCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)
Started161151600000
Completed140134560000
Not completed211740000
Withdrew: Lack of efficacy2210000
Withdrew: Withdrawal by subject9510000
Withdrew: Adverse event2510000
Withdrew: Protocol violation2000000
Withdrew: Lost to follow-up2100000
Withdrew: Death1000000
Withdrew: Physician decision1000000
Withdrew: Developed any malignancy0110000
Withdrew: Unmet predefined eligibility criteria2200000
Withdrew: Disease progression0100000
Extension Study Period
Participant flow — Extension Study Period
MilestoneCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)
Started000122646247
Completed000121646047
Not completed0001020
Withdrew: Withdrawal by subject0001020

Outcome measures

PrimaryAnalysis 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

Time frame:
over the first 24 weeks
Reported as:
Geometric least squares mean · h*μg/mL
Analysis of Serum AUC0-last of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
h*μg/mLCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)
Analysis of Serum AUC0-last of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)162414.81 ± 1.073167309.07 ± 1.073172450.97 ± 1.075
Statistical analysis
  • CT-P10 (Main Study Period) vs Rituxan (Main Study Period) · Ratio of geometric least squares means: 97.07 · 90% CI 88.08 to 106.99Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
  • CT-P10 (Main Study Period) vs MabThera (Main Study Period) · Ratio of geometric least squares means: 94.18 · 90% CI 85.40 to 103.86Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
  • Rituxan (Main Study Period) vs MabThera (Main Study Period) · Ratio of geometric least squares means: 103.07 · 90% CI 93.32 to 113.85Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
PrimaryAnalysis 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

Time frame:
at Week 24 of the Main Study Period
Reported as:
Geometric least squares mean · h*μg/mL
Analysis of Serum AUC0-inf of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
h*μg/mLCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)
Analysis of Serum AUC0-inf of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)162377.28 ± 1.068169480.80 ± 1.069180637.81 ± 1.072
Statistical analysis
  • CT-P10 (Main Study Period) vs Rituxan (Main Study Period) · Ratio of geometric least squares means: 95.81 · 90% CI 87.39 to 105.04Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
  • CT-P10 (Main Study Period) vs MabThera (Main Study Period) · Ratio of geometric least squares means: 89.89 · 90% CI 81.85 to 98.72Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
  • Rituxan (Main Study Period) vs MabThera (Main Study Period) · Ratio of geometric least squares means: 106.58 · 90% CI 97.03 to 117.08Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
PrimaryAnalysis 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

Time frame:
at Week 24 of the Main Study Period
Reported as:
Geometric least squares mean · ug/mL
Analysis of Serum Cmax of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
ug/mLCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)
Analysis of Serum Cmax of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)367.03 ± 1.042386.65 ± 1.042412.40 ± 1.043
Statistical analysis
  • CT-P10 (Main Study Period) vs Rituxan (Main Study Period) · Ratio of geometric least squares means: 94.92 · 90% CI 89.61 to 100.55Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
  • CT-P10 (Main Study Period) vs MabThera (Main Study Period) · Ratio of geometric least squares means: 89.00 · 90% CI 84.01 to 94.28Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
  • Rituxan (Main Study Period) vs MabThera (Main Study Period) · Ratio of geometric least squares means: 106.66 · 90% CI 100.56 to 113.13Point estimates (geometric least squares means and ratios of geometric means) were calculated by back-transforming the least squares means.
PrimaryAnalysis 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.

Time frame:
at Week 24 of the Main Study Period
Reported as:
Least squares mean · score on a scale
Analysis of Change From Baseline of DAS28 (CRP) at Week 24 (ANCOVA)
score on a scaleCT-P10 (Main Study Period)Reference Products (Main Study Period)
Analysis of Change From Baseline of DAS28 (CRP) at Week 24 (ANCOVA)-2.11 ± 0.176-2.10 ± 0.178
Statistical analysis
  • CT-P10 (Main Study Period) vs Reference Products (Main Study Period) · Mean difference (final values): -0.01 · 90% CI -0.22 to 0.20Adjusted least squares means and standard error, estimate of treatment difference \[CT-P10 - (Rituxan + MabThera)\] and 2-sided 90% confidence interval calculated from the ANCOVA model.
SecondaryDescriptive 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.

Time frame:
at Week 24 of the Main Study Period
Reported as:
Mean · score on a scale
Descriptive Statistics for Means (SD) for Baseline Value and Change From Baseline in Disease Activity Measured by DAS28 (CRP) of the Main Study Period
score on a scaleCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)Reference Products (Main Study Period)
Week 0 (Baseline)5.8 ± 0.915.8 ± 0.926.0 ± 0.875.8 ± 0.91
Week 24 (1st course Week 24)-2.3 ± 1.06-2.3 ± 1.11-2.3 ± 1.30-2.3 ± 1.17
Week 48 (2nd course Week 24)-2.7 ± 1.17-2.6 ± 1.32-2.7 ± 1.32-2.6 ± 1.32
SecondaryDescriptive 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.

Time frame:
at Week 24 of the Main Study Period
Reported as:
Mean · score on a scale
Descriptive Statistics for Means (SD) for Baseline Value and Change From Baseline in Disease Activity Measured by DAS28 (CRP) of the Extension Study Period
score on a scaleCT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension 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-3.0 ± 1.20-3.0 ± 1.32-2.9 ± 1.27-3.0 ± 1.11
SecondaryDescriptive 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.

Time frame:
at Week 24 of the Main Study Period
Reported as:
Mean · score on a scale
Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) of the Main Study Period
score on a scaleCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)Reference Products (Main Study Period)
Week 0 (Baseline)6.7 ± 0.836.7 ± 0.846.8 ± 0.756.7 ± 0.81
Week 24 (1st course Week 24)-2.5 ± 1.13-2.5 ± 1.13-2.3 ± 1.31-2.5 ± 1.18
Week 48 (2nd course Week 24)-2.9 ± 1.29-2.8 ± 1.42-2.9 ± 1.32-2.8 ± 1.39
SecondaryDescriptive 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.

Time frame:
at Week 24 of the Main Study Period
Reported as:
Mean · score on a scale
Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) of the Extension Study Period
score on a scaleCT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)
Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) of the Extension Study Period-3.3 ± 1.24-3.3 ± 1.41-3.2 ± 1.36-3.2 ± 1.15
SecondaryAnalysis 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.

Time frame:
Week 24
Reported as:
Geometric least squares mean · cells/mcL
Analysis of B-cell Counts at Week 24 of the Main Study Period (ANCOVA)
cells/mcLCT-P10 (Main Study Period)Reference Products (Main Study Period)
Analysis of B-cell Counts at Week 24 of the Main Study Period (ANCOVA)25.29 ± 1.07424.70 ± 1.073
Statistical analysis
  • CT-P10 (Main Study Period) vs Reference Products (Main Study Period) · Ratio of geometric least squares means: 102.37 · 95% CI 92.46 to 113.33

Adverse events

Collected over 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).. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CT-P10 (Main Study Period)1/161 (0.6%)13/161 (8.1%)88/161 (54.7%)
Rituxan (Main Study Period)0/151 (0%)14/151 (9.3%)72/151 (47.7%)
MabThera (Main Study Period)0/60 (0%)4/60 (6.7%)29/60 (48.3%)
CT-P10/CT-P10 (Extension Study Period)0/122 (0%)4/122 (3.3%)27/122 (22.1%)
Rituxan/Rituxan (Extension Study Period)0/64 (0%)0/64 (0%)16/64 (25%)
Rituxan/CT-P10 (Extension Study Period)0/62 (0%)1/62 (1.6%)17/62 (27.4%)
MabThera/CT-P10 (Extension Study Period)0/47 (0%)0/47 (0%)7/47 (14.9%)
Most frequent serious events
Showing 10 of 27
Most frequent serious events
EventCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)
FractureInjury, poisoning and procedural complications4/1612/1510/600/1220/640/620/47
OsteoarthritisMusculoskeletal and connective tissue disorders0/1610/1510/603/1220/640/620/47
LeukopeniaBlood and lymphatic system disorders0/1610/1511/600/1220/640/620/47
Adenocarcinoma of colonNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1610/1511/600/1220/640/620/47
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1611/1511/600/1220/640/620/47
LymphangiomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1610/1511/600/1220/640/620/47
PneumoniaInfections and infestations1/1611/1510/600/1220/641/620/47
InjuryInjury, poisoning and procedural complications0/1612/1510/600/1220/640/620/47
Infusion related reactionInjury, poisoning and procedural complications0/1610/1510/601/1220/640/620/47
Ligament sprainInjury, poisoning and procedural complications0/1610/1510/601/1220/640/620/47
Most frequent other events
Showing 10 of 17
Most frequent other events
EventCT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)
Infusion-related reactionInjury, poisoning and procedural complications33/16112/15113/604/1223/642/622/47
Upper respiratory tract infectionInfections and infestations24/16130/1519/6010/12210/648/620/47
Urinary tract infectionInfections and infestations15/1618/1512/608/1222/642/621/47
Lower respiratory tract infectionInfections and infestations10/1617/1513/601/1223/642/622/47
HeadacheNervous system disorders8/1618/1512/601/1220/640/621/47
PruritusSkin and subcutaneous tissue disorders3/1611/1513/600/1220/640/620/47
AnaemiaBlood and lymphatic system disorders6/1615/1512/601/1220/643/621/47
Alanine aminotransferase increasedInvestigations5/1617/1510/601/1220/641/620/47
HypertriglyceridaemiaMetabolism and nutrition disorders7/1614/1511/601/1221/640/620/47
RhinitisInfections and infestations3/1616/1511/600/1221/640/620/47

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)CT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)Total
<=18 years10000001
Between 18 and 65 years142127560000325
>=65 years18244000046
Age, Categorical
Age, Categorical(Participants)CT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)Total
<=18 years00010001
Between 18 and 65 years000105575244258
>=65 years00016710336
Age, Continuous
Age, Continuous(years)CT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)Total
Median53.0 (18 to 74)53.0 (21 to 74)51.5 (20 to 74)————53.0 (18 to 74)
Age, Continuous
Age, Continuous(years)CT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)Total
Median———52.5 (18 to 74)52.5 (24 to 68)53.0 (28 to 72)50.0 (20 to 69)52.0 (18 to 74)
Sex: Female, Male
Sex: Female, Male(Participants)CT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)Total
Female13813050————318
Male232110————54
Sex: Female, Male
Sex: Female, Male(Participants)CT-P10 (Main Study Period)Rituxan (Main Study Period)MabThera (Main Study Period)CT-P10/CT-P10 (Extension Study Period)Rituxan/Rituxan (Extension Study Period)Rituxan/CT-P10 (Extension Study Period)MabThera/CT-P10 (Extension Study Period)Total
Female———100545540249
Male———22107746
08

Study locations

No study locations are listed for this record.

09

References and documents

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. PubMed 31184752 ↗
  • 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. PubMed 30719632 ↗
  • 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. PubMed 30010481 ↗

Related links

Study documents

  • Study protocol · Apr 1, 2016
  • Statistical analysis plan · Mar 2, 2017

Documents are hosted by the registry — open the source record to download them.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 16, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02149121
Lead sponsor
Celltrion
Responsible party
Sponsor
First posted
May 29, 2014
Start date
Aug 2014
Primary completion
Jan 2016
Completion
Jan 2017
Results posted
Dec 16, 2021
Last update
Dec 16, 2021

Study contacts

DaeHyun Yoo, M.D., Ph.D
principal investigator · Hanyang University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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