A Randomized, Controlled, Multicenter, 2‑Arm, Parallel‑Group, Double-Blind Study To Demonstrate The Equivalence Of CT-P10 To Innovator Rituximab With Respect To Pharmacokinetic Profile In Patients With Rheumatoid Arthritis

Dae-Hyun Yoo¹, Won Park², Slawomir Jeka³, Fidencio Cons Molina⁴, Pawel Hrycaj⁵, Piotr Wiland⁶, Wolfgang Spieler⁷, Jan Brzezicki⁸, Eun Young Lee⁹, Francisco G. Medina-Rodriguez¹⁰, Pavel Shesternya¹¹, Sebastiao Radominski¹², Marina Stanislav¹³, Volodymyr Kovalenko¹⁴, Dong Hyuk Sheen¹⁵, Mie Jin Lim¹⁶, Jung-Yoon Choe¹⁷, Sung Young Lee¹⁸, Seung-Cheol Shim¹⁹ and Chang-Hee Suh²⁰, ¹Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, ²Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, South Korea, ³Clinic of Rheumatology and Connective Tissue Diseases University Hospital No 2 in Bydgoszcz Collegium Medicum UMK in Torun, Bydgoszcz, Poland, ⁴Centro de Investigacion en Artritis y Osteoporosis, Mexicali, Mexico, ⁵Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland, ⁶Department of Rheumatology, Medical University of Wroclaw, Wroclaw, Poland, ⁷Osteologie und Rheumatologie, ZeFOR GmbH Zentrum für Forschung, Zerbst, Germany, ⁸Wojewodzki Szpital Zespolony Oddzial Reumatologiczny, Elblag, Poland, ⁹Internal medicine, Division of Rheumatology, Department of Internal Medicine, Seoul National University, Seoul, South Korea, ¹⁰Centro de Investigación Farmacológica y Biotecnológica, Mexico City, Mexico, ¹¹Rheumatology Department, Krasnoyarsk State Medical University, Krasnoyarsk, Russia, ¹²CETI Centro de Estudos em Terapias Inovadoras Ltda, Curitiba, Brazil, ¹³Central Russian National Institute of Rheumatology, Russian Academy of Medical Science, Moscow, Russia, ¹⁴Section of Non-coronarogenic Myocardial Diseases and Clinical Rheumatology, National Scientific Center, Kiev, Ukraine, ¹⁵Rheumatology, Eulji University Hospital, DaeJeon, South Korea, ¹⁶Division of Rheumatology, Department of Internal Medicine,, Inha University Hospital, Incheon, South Korea, ¹⁷Rheumatology, Daegu Catholic University Medical Center, Daegu, South Korea, ¹⁸Clinical Planning and Medical Affairs Department, CELLTRION, Inc., Incheon, South Korea, ¹⁹Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea, ²⁰Department of Rheumatology, Ajou University Hospital, Suwon, South Korea

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Biologic drugs, Biologics, rheumatoid arthritis (RA) and rituximab

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy: Efficacy and Safety of Novel Entities

Session Type: Abstract Submissions (ACR)

Background/Purpose: CT-P10 was developed as a biosimilar candidate to innovator rituximab (RTX), an anti-CD20 monoclonal antibody. This trial is a phase I study to demonstrate the equivalence of the pharmacokinetic (PK) profile of CT-P10 with RTX in patients with active rheumatoid arthritis (RA) who had an inadequate response or intolerant to previous antitumor necrosis factor (TNF) agents. Equivalence will be concluded if the 90% Confidence Intervals (CI) for the ratios of the geometric means of AUC_0–last and C_max between the CT-P10 and RTX groups are within 80%– 125%. The pharmacodynamics (PD), efficacy, and overall safety of both treatments were also evaluated.

Methods: One hundred and fifty-four patients with active RA were randomized 2:1 to receive 2 infusions (1000 mg, IV each) of either CT-P10 (n=103) or RTX (n=51) with a 2-week interval between infusions, both co-administered with weekly methotrexate and folic acid. The primary endpoints were area under the serum concentration-time curve from time ‘0’ to time of last quantifiable concentration (AUC_0–last) and maximum serum concentration (C_max) (after second infusion) of the CT-P10 and RTX groups. ACR response, EULAR response, B-cell kinetics, immunogenicity and safety parameters were also evaluated up to week 24.

Results: The geometric means were 7870.84 day-µg/mL and 8010.39 day-µg/mL for AUC_0–last and 465.94 µg/mL and 477.52 µg/mL for C_maxin the CT-P10 and RTX groups, respectively. The ratios (%) of the geometric means of AUC_0–last and C_max between the CT-P10 and RTX groups were 98.3% (90% CI: 89.6, 107.8) and 97.6% (90% CI: 92.0, 103.5), respectively.

The geometric mean area under the curve (AUC) of B-cell count, a comparative PD parameter, was 20.8 cells/µL for the CT-P10 group and 20.4 cells/µL for the RTX group. The ratio (%) of the geometric means of AUC for B-cell count was 102% (90% CI: 98, 106). ACR20/50/70 response rates at week 24 were 63.0%/37.0%/16.0% in the CT-P10 group and 66.7%/31.3%/14.6% in the RTX group. The proportions of patients who had a moderate or good response at week 24 were 76.8% and 79.1% for EULAR (ESR) response and 82.1% and 83.7% for EULAR (CRP) response in the CT-P10 and RTX groups, respectively.

The proportions of patients with a positive anti-drug antibody at week 24 were 17.6% (18/102) for the CT-P10 group and 17.6% (9/51) for the RTX group. A total of 166 and 88 treatment-emergent adverse events were reported for the CT-P10 and RTX groups, respectively. Serious adverse events were reported in 16.7% of CT-P10 and 17.6% of RTX patients. Infections were reported in 23.5% of CT-P10 and 25.5% of RTX patients. Infusion reactions were reported in 16.7% of CT-P10 and 19.6% of RTX patients.

Conclusion: CT-P10 and RTX were equivalent in terms of AUC_0–last and C_max in patients with active RA. Clinical efficacy for ACR20/50/70 and EULAR response rates and PD for B-cell kinetics were comparable between the two treatment groups. CT-P10 was well tolerated with a safety profile comparable to that of RTX up to week 24.

Disclosure:

D. H. Yoo,

CELLTRION, Inc,

W. Park,

CELLTRION, Inc.,

S. Jeka,

CELLTRION, Inc.,

F. Cons Molina,

CELLTRION, Inc.,

P. Hrycaj,

CELLTRION, Inc.,

P. Wiland,

CELLTRION, Inc.,

W. Spieler,

CELLTRION, Inc,

J. Brzezicki,

CELLTRION, Inc,

E. Y. Lee,

CELLTRION, Inc,

F. G. Medina-Rodriguez,

CELLTRION, Inc.,

P. Shesternya,

CELLTRION, Inc.,

S. Radominski,

CELLTRION, Inc.,

M. Stanislav,

CELLTRION, Inc.,

V. Kovalenko,

CELLTRION, Inc.,

D. H. Sheen,

CELLTRION, Inc.,

M. J. Lim,

CELLTRION, Inc.,

J. Y. Choe,

CELLTRION, Inc.,

S. Y. Lee,

CELLTRION, Inc.,

S. C. Shim,

CELLTRION, Inc.,

C. H. Suh,

CELLTRION, Inc.,

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