ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1736

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: , ,

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 AUC0–last and Cmax 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 (AUC0–last) and maximum serum concentration (Cmax) (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 AUC0–last and 465.94 µg/mL and 477.52 µg/mL for Cmax in the CT-P10 and RTX groups, respectively. The ratios (%) of the geometric means of AUC0–last and Cmax 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 AUC0–last and Cmax 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,

5;

W. Park,

CELLTRION, Inc.,

5;

S. Jeka,

CELLTRION, Inc.,

2;

F. Cons Molina,

CELLTRION, Inc.,

2;

P. Hrycaj,

CELLTRION, Inc.,

2;

P. Wiland,

CELLTRION, Inc.,

2;

W. Spieler,

CELLTRION, Inc,

2;

J. Brzezicki,

CELLTRION, Inc,

2;

E. Y. Lee,

CELLTRION, Inc,

2;

F. G. Medina-Rodriguez,

CELLTRION, Inc.,

2;

P. Shesternya,

CELLTRION, Inc.,

2;

S. Radominski,

CELLTRION, Inc.,

2;

M. Stanislav,

CELLTRION, Inc.,

2;

V. Kovalenko,

CELLTRION, Inc.,

2;

D. H. Sheen,

CELLTRION, Inc.,

2;

M. J. Lim,

CELLTRION, Inc.,

2;

J. Y. Choe,

CELLTRION, Inc.,

2;

S. Y. Lee,

CELLTRION, Inc.,

3;

S. C. Shim,

CELLTRION, Inc.,

2,

CELLTRION, Inc.,

5;

C. H. Suh,

CELLTRION, Inc.,

2,

CELLTRION, Inc.,

5.

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