Clinical trial NCT02149121: PK Similarity Prospective Phase 3 Study in Patients With Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Celltrion
Sponsor class: INDUSTRY
First posted: 2014-05-29
Enrollment: 384
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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:

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.

Primary outcomes:
measure: Analysis of Serum AUC0-last of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
timeFrame: over the first 24 weeks
measure: Analysis of Serum AUC0-inf of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
timeFrame: at Week 24 of the Main Study Period
measure: Analysis of Serum Cmax of Rituximab During the 1st Course of the Main Study Period (Over the First 24 Weeks) (ANCOVA)
timeFrame: at Week 24 of the Main Study Period
measure: Analysis of Change From Baseline of DAS28 (CRP) at Week 24 (ANCOVA)
timeFrame: at Week 24 of the Main Study Period
Secondary outcomes:
measure: Descriptive Statistics for Means (SD) for Baseline Value and Change From Baseline in Disease Activity Measured by DAS28 (CRP) of the Main Study Period
timeFrame: at Week 24 of the Main Study Period
measure: Descriptive Statistics for Means (SD) for Baseline Value and Change From Baseline in Disease Activity Measured by DAS28 (CRP) of the Extension Study Period
timeFrame: at Week 24 of the Main Study Period
measure: Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) of the Main Study Period
timeFrame: at Week 24 of the Main Study Period
measure: Descriptive Statistics for Actual Value and Change From Baseline in Disease Activity Measured by DAS28 (ESR) of the Extension Study Period
timeFrame: at Week 24 of the Main Study Period
measure: Analysis of B-cell Counts at Week 24 of the Main Study Period (ANCOVA)
timeFrame: Week 24
Other outcomes:
Locations:
Study officials:
affiliation: Hanyang University
name: DaeHyun Yoo, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.