The primary endpoint was to demonstrate equivalent efficacy of CT-P13 to INX at week 30, as determined by ACR20 response criteria. Equivalence of efficacy was concluded if the 95% CIs for treatment difference were within ±15% at week 30.
Secondary endpoints included additional efficacy, immunogenicity, safety, PK and PD parameters. Clinical assessments of disease activity, including the additional measures: ACR individual component scores; ACR20/ACR50/ACR70; time-to-onset of ACR20; mean decrease in Disease Activity Score 28 (DAS28); European League Against Rheumatism (EULAR) response criteria; Clinical Disease Activity Index (CDAI); Simplified Disease Activity Index (SDAI) and general health status (Medical Outcomes Study Short-Form Health Survey (SF-36)), were performed before infusion at baseline, weeks 14 and 30. A post hoc analysis of ACR–EULAR remission rate at week 30 was also performed.4 (link)
Blood samples collected at screening and weeks 14 and 30 were assessed for antidrug antibodies (ADA), and a post hoc analysis of endpoints by ADA status was conducted. Immunogenicity testing used both the CT-P13 tag and INX tag (see online supplementary appendix C). Antibodies against CT-P13 or INX were measured using an electrochemiluminescent immunoassay method using the Meso Scale Discovery platform (MSD, Rockville, Maryland, USA).
Safety endpoints included incidence and type of adverse events (AEs) and infection, serious AEs, incidence of infusion-related reactions and changes from baseline in clinical laboratory parameters. AEs were coded using the Medical Dictionary for Regulatory Activities and severity was characterised as mild, moderate or severe.
All patients were screened for latent or active tuberculosis (TB) by an interferon γ-release assay using QuantiFERON-TB Gold in tube (QTF-TB Gold-IT, Cellestis, Australia) and chest x-ray and monitored for any clinical signs and symptoms of TB at each planned visit. Patients with latent TB received prophylactic medication before and during the study period according to country-specific guidelines. For countries with an increased incidence of TB, QTF-TB Gold-IT was used at weeks 14 and 30 to identify positive conversion from negative results at baseline, according to WHO recommendations for sole use of interferon γ-release assay in non-HIV adults receiving anti-TNF therapy.5
6
PK endpoints included Cmax, Cmin, Cav,ss, peak to trough fluctuation ratio and time to reach Cmax (Tmax). PD endpoints included concentrations of serum CRP, rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) and ESR. Serum blood samples were obtained immediately before each dosing for PK and PD analyses, and at the end and 1 h after the end of each treatment infusion for PK analysis. All PK analyses were conducted using a flow-through immunoassay platform (GyrolabxP; Gyros AB, Sweden).
Secondary endpoints included additional efficacy, immunogenicity, safety, PK and PD parameters. Clinical assessments of disease activity, including the additional measures: ACR individual component scores; ACR20/ACR50/ACR70; time-to-onset of ACR20; mean decrease in Disease Activity Score 28 (DAS28); European League Against Rheumatism (EULAR) response criteria; Clinical Disease Activity Index (CDAI); Simplified Disease Activity Index (SDAI) and general health status (Medical Outcomes Study Short-Form Health Survey (SF-36)), were performed before infusion at baseline, weeks 14 and 30. A post hoc analysis of ACR–EULAR remission rate at week 30 was also performed.4 (link)
Blood samples collected at screening and weeks 14 and 30 were assessed for antidrug antibodies (ADA), and a post hoc analysis of endpoints by ADA status was conducted. Immunogenicity testing used both the CT-P13 tag and INX tag (see online supplementary appendix C). Antibodies against CT-P13 or INX were measured using an electrochemiluminescent immunoassay method using the Meso Scale Discovery platform (MSD, Rockville, Maryland, USA).
Safety endpoints included incidence and type of adverse events (AEs) and infection, serious AEs, incidence of infusion-related reactions and changes from baseline in clinical laboratory parameters. AEs were coded using the Medical Dictionary for Regulatory Activities and severity was characterised as mild, moderate or severe.
All patients were screened for latent or active tuberculosis (TB) by an interferon γ-release assay using QuantiFERON-TB Gold in tube (QTF-TB Gold-IT, Cellestis, Australia) and chest x-ray and monitored for any clinical signs and symptoms of TB at each planned visit. Patients with latent TB received prophylactic medication before and during the study period according to country-specific guidelines. For countries with an increased incidence of TB, QTF-TB Gold-IT was used at weeks 14 and 30 to identify positive conversion from negative results at baseline, according to WHO recommendations for sole use of interferon γ-release assay in non-HIV adults receiving anti-TNF therapy.5
6
PK endpoints included Cmax, Cmin, Cav,ss, peak to trough fluctuation ratio and time to reach Cmax (Tmax). PD endpoints included concentrations of serum CRP, rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) and ESR. Serum blood samples were obtained immediately before each dosing for PK and PD analyses, and at the end and 1 h after the end of each treatment infusion for PK analysis. All PK analyses were conducted using a flow-through immunoassay platform (GyrolabxP; Gyros AB, Sweden).
