PK Similarity Prospective Phase 3 Study in Patients With Rheumatoid Arthritis

NCT02149121 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CT-P10 3.22013-004555-21
• Study Type: interventional
• Target: 384
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (4)

• 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)

  For evaluation of efficacy, the primary endpoint was defined as the analysis of change from baseline in disease activity measured by disease activity score 28 (DAS 28) C-reactive protein (CRP) at Week 24 between 2 treatment groups, CT-P10 and reference products (combined Rituxan and MabThera) groups. During the 1st course of the Main Study Period, DAS28 was assessed every 4 weeks from Week 0 to Week 24. DAS28 (CRP) was calculated using the following formula: DAS28 (CRP) = 0.56 X SQRT(TJC28) + 0.28 X SQRT(SJC28) + 0.36 X ln(CRP+1) + 0.014 X GH on VAS + 0.96. DAS28 (CRP) provides a number on a scale from 0 to 10 with higher values indicating greater RA disease activity.

  at Week 24 of the Main Study Period

Secondary 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

  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

  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

  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

  at Week 24 of the Main Study Period

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

  Week 24

Study Arms (3)

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

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

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

Biological: CT-P10; Drug: MabThera

Interventions

CT-P10 BIOLOGICAL

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

Also known as: rituximab

CT-P10; MabThera; Rituxan

Rituxan DRUG

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

Rituxan

MabThera DRUG

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

MabThera

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celltrion: lead

Related Publications (3)

• 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.

  PMID: 31184752 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.

  PMID: 30719632 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.

  PMID: 30010481 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

CT-P10; Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: SungYoung Lee
• Organization: Celltrion, Inc.

SungYoung.Lee@celltrion.com

+82 32 850 6532

Study Officials

• DaeHyun Yoo, M.D., Ph.D

  Hanyang University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2014
• First Posted: May 29, 2014
• Study Start: August 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2017
• Last Updated: December 16, 2021
• Results First Posted: December 16, 2021

Record last verified: 2017-05