THU0191 Novel formulation of ct-p13 for subcutaneous administration in patients with rheumatoid arthritis: initial results from a phase i/iii randomised controlled trial

Abstract

BackgroundWhile the treatment with intravenous (IV) CT-P13, an infliximab biosimilar, is effective and well tolerated, a new subcutaneous (SC) CT-P13 formulation (CT-P13 SC) is developed to provide additional, more convenient treatment options and opportunity for self-injection.ObjectivesTo find the optimal dose of CT-P13 SC and to evaluate efficacy, PK and safety over the first 30 weeks in patients with rheumatoid arthritis.MethodsThis study consists of 1 cohort with CT-P13 IV, and 3 cohorts with 3 different doses of CT-P13 SC injected biweekly. All enrolled patients initially received CT-P13 IV at Weeks 0 and 2 and patients who received 2 full doses and displayed no safety concerns were randomly assigned to receive either CT-P13 SC or IV at Week 6. Using part 1 result, PK-PD modelling was conducted for the 3 regimens.ResultsA total of 50 patients were enrolled, of whom 48 patients were randomly assigned into 4 cohorts.Overall, the efficacy results of CT-P13 SC up to Week 30 were comparable to those of CT-P13 IV. Disease improvement by DAS28 and ACR20 were comparable across all 4 cohorts, regardless of the route of administration or dosage of CT-P13 (table 1).The safety profiles in CT-P13 SC cohorts were generally comparable to CT-P13 IV. One of the 2 patients who experienced a hypersensitivity reaction became anti-drug antibody (ADA) positive at Week 6 and experienced hypersensitivity from Week 2 to 8. All injection site reactions were grade 1 or 2. The proportion of ADA (positive) was lower in the SC cohorts.In PK-PD modelling, bioavailability was 59% (95% CI, 52%–67%). The dose linearity in SC regimens was confirmed based on Weeks 22 to 30 Ctrough, AUCτ and Cmax, ss (figure 1). Ctrough were greater (above 4 µg/mL) than the target exposure (1 µg/mL)[1][2] in all SC regimens. There was a trend towards slightly lower DAS28 score in all SC regimens, which was consistent with the higher Ctrough comparing with CT-P13 IV. Based on the exposure-response safety analyses, there was no correlation between PK (AUCτ or Cmax) and safety (IRRs or infections).Abstract THU0191 – Table 1Efficacy and safety up to Week 30Cohort 1IV 3 mg/kg(n=13)Cohort 2SC 90 mg(n=11)Cohort 3SC 120 mg(n=12)Cohort 4SC 180 mg(n=12) DAS28 (CRP), mean±SDWeek 05.4±0.86.3±0.85.7±0.95.5±0.8 Week 63.9±1.54.6±1.13.9±1.23.4±1.2Week 223.9±1.63.7±1.03.3±1.42.8±1.3Week 303.3±1.33.0±1.13.1±1.02.7±1.0ACR20,n (%)Week 68 (61.5)8 (72.7)7 (58.3)7 (58.3)Week 228 (61.5)8 (72.7)9 (75.0)11 (91.7)Week 3011 (84.6)10 (90.9)10 (83.3)12 (100)Safety, n (%)Hypersensitivity/IRR01 (9.1)1 (8.3)0Injection site reactions02 (18.2)02 (16.7)Infections4 (30.8)2 (18.2)04 (33.3)ADA9 (69.2)3 (27.3)4 (33.3)1 (8.3)Abstract THU0191 – Figure 1Mean (± SD) Simulated CT-P13 Serum Concentration vs Time Profiles for the Simulated Fixed Dose SC Maintenance Dosing Regimens with Overlaid IV Maintenance Reference Treatment (Semi-Logarithmic Scale). Solid line=Period 1 (IV reference regimen: IV loading+IV maintenance dose). Dashed line=Period 2 (SC test regimen: IV loading+SC maintenance dose)Abstract ...

Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease

“…The relatively stable mean serum concentrations observed at steady state with CT-P13 SC treatment were as anticipated based on the pharmacokinetic properties of the SC formulation. 27 Mean observed C trough consistently exceeded the target after patients in the CT-P13 IV arm switched to CT-P13 SC at W30. The increased C trough for CT-P13 SC vs CT-P13 IV may be postulated to translate into higher efficacy.…”

TNF-Alpha Blockers in Inflammatory Bowel Diseases: Practical Recommendations and a User’s Guide: An Update

“…A subcutaneous formulation of the IFX biosimilar (BS) CT-P13 (Celltrion) may soon be available for phase 3 clinical studies in the rheumatoid arthritis population [38], and a phase 1 study in the CD population has been recently conducted [39].…”

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

“…Gains from biosimilar development could also be extended through the use of innovative approaches, such as the development of more convenient or longer-acting drug formulations, as conducted by RP manufacturers [7]. For example, infliximab biosimilars are currently administered intravenously, but a subcutaneous formulation of CT-P13 that could offer increased convenience for patients is in development [187][188][189]. Adding value to a product and dedication to an evidence-based approach will be key factors in determining the future success and sustainability of a developer in the competitive biosimilars market.…”