Fri0128 a Novel Formulation of Ct-P13 (Infliximab Biosimilar) for Subcutaneous Administration: 1-Year Results From a Part 1 of Phase I/Iii Randomized Controlled Trial in Patients With Active Rheumatoid Arthritis

Abstract

BackgroundEfficacy and safety of a new subcutaneous (SC) formulation (CT-P13 SC) up to Week 30 were comparable with intravenous (IV) formulation (CT-P13 IV) in both patients with rheumatoid arthritis (RA) [1] and Crohn's disease [2].ObjectivesThis report is to further investigate pharmacokinetics, efficacy and overall safety of CT-P13 SC in patients with RA throughout the 1-year treatment period.MethodsPatients with active RA (presence of 6 or more swollen and tender joints [of 28 assessed], and serum C-reactive protein [CRP] concentration >0.6 mg/dL) were treated with CT-P13 IV at Weeks 0 and 2, and were randomized for continuation with CT-P13 IV or SC administration at Week 6. The IV cohort received CT-P13 IV 3 mg/kg every 8 weeks and the SC cohorts received CT-P13 SC 90 mg, 120 mg or 180 mg, respectively, every 2 weeks up to Week 54. Pharmacokinetics blood samples were collected before study drug administration at each visit and drug levels were determined by electrochemiluminescent assay. Efficacy parameters including DAS28 and ACR criteria and overall safety were evaluated.ResultsA total of 50 patients were enrolled, of whom 48 patients were randomly assigned at Week 6 into 4 cohorts (1:1:1:1 ratio). The mean Ctrough (pre-dose serum concentration of CT-P13 before next dose injection) of SC cohorts throughout the study visits were higher than those of IV cohort after randomization at Week 6. Ctrough levels increased with SC dose and were sufficiently higher than the target therapeutic concentration (1 μg/mL) throughout the study period (Figure 1). Overall, the efficacy results of CT-P13 SC up to Week 54 were comparable to those of CT-P13 IV. Disease improvement by DAS28 (CRP) and ACR20 were comparable across all 4 cohorts, regardless of the route of administration or dosage of CT-P13 (Table 1). The safety profiles which occurred after study drug administration at Week 6 in SC cohorts were generally comparable to those of IV cohort and appeared similar to those previously reported for IV infliximab [3]. All injection site reactions were grade 1 or 2. No malignancy or death was reported (Table 1).ConclusionThe results from 1-year treatment suggest similar efficacy and safety of CT-P13 SC to CT-P13 IV in RA. The mean serum concentration in all SC cohorts consistently exceeded the threshold of target therapeutic concentration. These results show that the novel SC formulation of CT-P13 may enhance treatment options for use of infliximab biosimilar by providing high consistency in drug exposure.Reference1Westhovens et al., Annals of the Rheumatic Disease 2018;77:315.2Schreiber et al., Gastroenterology 2018;154(6):S-1371.3Yoo et al., Arthritis Research & Therapy 2016;18:82. Disclosure of InterestsDaeHyun Yoo Grant/research support from: Celltrion, Inc., Consultant for: Celltrion, Inc., Janusz Jaworski Grant/research support from: Celltrion, Inc., Ewa Matyska-Piekarska Grant/research support from: Celltrion, Inc., Svitlana Smiyan Grant/research support from: Celltrion, Inc., Delina Ivanova Grant/research support from:...

Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters

“… 22 Efficacy up to Week 54 was similar between treatment arms in terms of mean DAS28 (CRP) scores, even after the CT-P13 IV group switched to CT-P13 SC at Week 30. 22 In terms of PK, mean serum concentrations consistently exceeded the threshold target–therapeutic concentration in Part 1 19 and Part 2. 22 Drug exposure was well maintained, with trough serum concentrations higher and more constant with CT-P13 SC versus CT-P13 IV: 19 , 22 this high consistency in drug exposure could enhance treatment options for patients.…”

“… 22 In terms of PK, mean serum concentrations consistently exceeded the threshold target–therapeutic concentration in Part 1 19 and Part 2. 22 Drug exposure was well maintained, with trough serum concentrations higher and more constant with CT-P13 SC versus CT-P13 IV: 19 , 22 this high consistency in drug exposure could enhance treatment options for patients. 19 In addition, overall safety profiles were comparable between arms for both study parts.…”

“…The Phase I CT-P13 SC 1.6 study was conducted in patients with inflammatory bowel disease (IBD): Part 1 was a dose-finding study, conducted in patients with CD, 15 and Part 2 evaluated non-inferiority in terms of PK in patients with CD or UC. 16 The Phase I/III CT-P13 SC 3.5 study, conducted in patients with RA, comprised two Parts: Part 1 was dose-finding study, 19 while Part 2 established non-inferiority of CT-P13 SC versus CT-P13 IV in terms of efficacy and evaluated a single switch from CT-P13 IV to CT-P13 SC (Supplementary Figure 5 shows the study design). 22 While the aforementioned studies administered CT-P13 SC via prefilled syringe, administration of CT-P13 SC via autoinjector was assessed as an alternative in the Phase I CT-P13 SC 1.9 study in healthy volunteers.…”

“…In Part 1 of the CT-P13 SC 3.5 study, efficacy profiles were similar for CT-P13 SC and CT-P13 IV arms up to Week 54. 19 In Part 2, non-inferiority between treatments was concluded for the primary efficacy endpoint, change from baseline to Week 22 in Disease Activity Score in 28 joints (DAS28)-(C-reactive protein [CRP]), since the lower limit of the 95% CI for the estimate of treatment difference (0.27 [95% CI: 0.02–0.52]) exceeded the prespecified non-inferiority margin of −0.6. 22 In addition, ACR response rates were similar between treatment arms up to Week 22.…”

Clinical Benefits of Switching from Original Infliximab to its Biosimilar (CT-P13) as a Potential TNF-α Inhibitor

“…They also discussed the results collected from clinical trials phase I/III studies from June 2018 to August 2018 in their entirity. 43 Celltrion, a South Korean biotechnology company, conducted the research of one year and reported the pharmacokinetics, efficacy and overall safety data of subcutaneous form of CT-P13 in rheumatoid arthritis. 44 Financial gains with the implementation of a biosimilar concept were noticed from the economic budget standpoint and have drawn the attention of economists.…”