NOVEL FORMULATION OF CT-P13 FOR SUBCUTANEOUS ADMINISTRATION IN PATIENTS WITH RHEUMATOID ARTHRITIS: INITIAL RESULTS FROM A PHASE I/III RANDOMISED CONTROLLED TRIAL

Abstract

Background While 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.

Objectives To 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.

Methods This 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.

Results A 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).