A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study

Abstract

Objectives: To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS).

Methods: Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed.

Results: Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively.

Conclusions: The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.

Figure 1

Flowchart of patient disposition. A total of 370 patients were screened for the study, and 250 eligible patients were randomised to the CT-P13 group (N=125), and the innovator infliximab (INX) group (N=125) to receive 5 mg/kg of CT-P13 or INX, respectively. All 250 randomly assigned patients were included in the intent-to-treat population. *Seven patients (three from CT-P13 group, four from INX group) from a potentially fraudulent study site were excluded from analyses.

Figure 2

Mean (±SD) serum concentrations of innovator infliximab (INX) and CT-P13 versus time by treatment. Serum concentration of drug was measured using a flow-through immunoassay platform (GyrolabxP). Mean serum drug concentration profiles of CT-P13 and INX were plotted by treatment on scheduled sample times. (A) Mean serum drug concentration following administration of Dose 5 (10 scheduled sample times between weeks 22 and 30) of CT-P13 (5 mg/kg) or INX (5 mg/kg). (B) Mean serum drug concentration of CTP13 and INX following administration of Doses 1–6. Blood samples were obtained 15 min prior to infusion, at the end of the infusion and 1 h postinfusion.