Rheumatoid ArthritisPhase 3rituximabNCT02149121

PK Similarity Prospective Phase 3 Study in Patients With Rheumatoid Arthritis

A Phase 3 study testing CT-P10, Rituxan and MabThera in people with Rheumatoid Arthritis, run by Celltrion.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: CT-P10, Rituxan and MabThera
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 384 participants
Where: No sites listed yet
Study dates: Aug 2014to Jan 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

About this study

Official title: 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

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

Conditions: Rheumatoid Arthritis
Being tested: CT-P10, Rituxan, MabThera
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CT-P10Biological
Also called rituximab
1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion
RituxanDrug
Also called rituximab
US-licensed reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion
MabTheraDrug
Also called rituximab
EU-approved reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion

Study groups in NCT02149121
Study group	Role	What they receive
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 Receives: Biological: CT-P10
Rituxan	Active comparator	US-licensed referece product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusions Receives: Biological: CT-P10; Drug: Rituxan
MabThera	Active comparator	EU-approved reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusions Receives: Biological: CT-P10; Drug: MabThera

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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
Measured: at Week 24 of the Main Study Period
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.
Measured: at Week 24 of the Main Study Period

Secondary outcomes (5)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2014Jan 2017

First posted29 May 2014 (estimated)
Study startAug 2014
Primary completionJan 2016
Study completionJan 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 384 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02149121
Sponsor's protocol ID: CT-P10 3.2
Other IDs: 2013-004555-21
Acronym: rituximab
Status last verified: May 2017
First submitted: 23 May 2014
Last updated: 16 Dec 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02149121
Acronym / sponsor ID: rituximab / CT-P10 3.2
Conditions: Rheumatoid Arthritis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 384 participants (actual)
Lead sponsor: CelltrionIndustry (pharma, biotech, devices)
Study start: Aug 2014 (actual)
Primary completion: Jan 2016 (actual)
Study completion: Jan 2017 (actual)
First posted: 29 May 2014 (estimated)
Results: Posted 16 Dec 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
CT-P10	Experimental	Biological: CT-P10rituximab, CT-P10(experimental drug), 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion
Rituxan	Active comparator	Biological: CT-P10, Drug: RituxanUS-licensed referece product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusions
MabThera	Active comparator	Biological: CT-P10, Drug: MabTheraEU-approved reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusions

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CT-P10Also: rituximab1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion	Biological	CT-P10, MabThera, Rituxan
RituxanAlso: rituximabUS-licensed reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion	Drug	Rituxan
MabTheraAlso: rituximabEU-approved reference product, 1000mg by intravenous infusion. 2 infusions with a 2-week interval between the first and second infusion	Drug	MabThera

Primary outcome

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
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
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
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.

5 secondary outcomes

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
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
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
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
Analysis of B-cell Counts at Week 24 of the Main Study Period (ANCOVA)
Time frame: Week 24

Results and safety

Results posted to the registry on 16 Dec 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CT-P10 (Main Study Period)	161	140
Rituxan (Main Study Period)	151	134
MabThera (Main Study Period)	60	56
CT-P10/CT-P10 (Extension Study Period)	0	0
Rituxan/Rituxan (Extension Study Period)	0	0
Rituxan/CT-P10 (Extension Study Period)	0	0
MabThera/CT-P10 (Extension Study Period)	0	0

Primary outcome: 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. Geometric least squares mean (Standard Error). Unit: h*μg/mL

Measure	CT-P10 (Main Study Period) n = 62	Rituxan (Main Study Period) n = 60	MabThera (Main Study Period) n = 59
Value	162414.81 (1.073)	167309.07 (1.073)	172450.97 (1.075)

CT-P10 (Main Study Period) vs Rituxan (Main Study Period): Ratio of geometric least squares means: 97.07 (90% CI 88.08 to 106.99)
CT-P10 (Main Study Period) vs MabThera (Main Study Period): Ratio of geometric least squares means: 94.18 (90% CI 85.40 to 103.86)
Rituxan (Main Study Period) vs MabThera (Main Study Period): Ratio of geometric least squares means: 103.07 (90% CI 93.32 to 113.85)

Population analysed: 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.

Primary outcome: 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. Geometric least squares mean (Standard Error). Unit: h*μg/mL

Measure	CT-P10 (Main Study Period) n = 59	Rituxan (Main Study Period) n = 60	MabThera (Main Study Period) n = 56
Value	162377.28 (1.068)	169480.80 (1.069)	180637.81 (1.072)

CT-P10 (Main Study Period) vs Rituxan (Main Study Period): Ratio of geometric least squares means: 95.81 (90% CI 87.39 to 105.04)
CT-P10 (Main Study Period) vs MabThera (Main Study Period): Ratio of geometric least squares means: 89.89 (90% CI 81.85 to 98.72)
Rituxan (Main Study Period) vs MabThera (Main Study Period): Ratio of geometric least squares means: 106.58 (90% CI 97.03 to 117.08)

Primary outcome: 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. Geometric least squares mean (Standard Error). Unit: ug/mL

Measure	CT-P10 (Main Study Period) n = 62	Rituxan (Main Study Period) n = 59	MabThera (Main Study Period) n = 59
Value	367.03 (1.042)	386.65 (1.042)	412.40 (1.043)

CT-P10 (Main Study Period) vs Rituxan (Main Study Period): Ratio of geometric least squares means: 94.92 (90% CI 89.61 to 100.55)
CT-P10 (Main Study Period) vs MabThera (Main Study Period): Ratio of geometric least squares means: 89.00 (90% CI 84.01 to 94.28)
Rituxan (Main Study Period) vs MabThera (Main Study Period): Ratio of geometric least squares means: 106.66 (90% CI 100.56 to 113.13)

Primary outcome: Analysis of Change From Baseline of DAS28 (CRP) at Week 24 (ANCOVA)

Time frame: at Week 24 of the Main Study Period. Least squares mean (Standard Error). Unit: score on a scale

Measure	CT-P10 (Main Study Period) n = 138	Reference Products (Main Study Period) n = 196
Value	-2.11 (0.176)	-2.10 (0.178)

CT-P10 (Main Study Period) vs Reference Products (Main Study Period): Mean Difference (Final Values): -0.01 (90% CI -0.22 to 0.20)

Population analysed: 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.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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).. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CT-P10 (Main Study Period)	13 of 161 (8.1%)	88 of 161 (54.7%)	1 of 161
Rituxan (Main Study Period)	14 of 151 (9.3%)	72 of 151 (47.7%)	0 of 151
MabThera (Main Study Period)	4 of 60 (6.7%)	29 of 60 (48.3%)	0 of 60
CT-P10/CT-P10 (Extension Study Period)	4 of 122 (3.3%)	27 of 122 (22.1%)	0 of 122
Rituxan/Rituxan (Extension Study Period)	0 of 64 (0%)	16 of 64 (25%)	0 of 64
Rituxan/CT-P10 (Extension Study Period)	1 of 62 (1.6%)	17 of 62 (27.4%)	0 of 62
MabThera/CT-P10 (Extension Study Period)	0 of 47 (0%)	7 of 47 (14.9%)	0 of 47

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31184752Shim 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.
Derived from this study: PubMed 30719632Suh 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.
Derived from this study: PubMed 30010481Park 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.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

DaeHyun Yoo, M.D., Ph.D principal investigator

Hanyang University

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CT-P10, Rituxan and MabThera in people with Rheumatoid Arthritis, run by Celltrion.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02149121, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2021.