Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial

Abstract

Objective To assess non-inferiority of s.c. to i.v. CT-P13 in RA. Methods Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46–54) then PFS (W56–64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: −0.6). Results Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS. Conclusion CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.

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.…”

“… 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. 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 addition, ACR response rates were similar between treatment arms up to Week 22. 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 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.…”

“…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. 23 …”