Phase 3, open‐label, randomized study of the pharmacokinetics, efficacy and safety of ixekizumab following subcutaneous administration using a prefilled syringe or an autoinjector in patients with moderate‐to‐severe plaque psoriasis (UNCOVER‐A)

Abstract

BackgroundThe efficacy of ixekizumab, an anti‐interleukin‐17A (anti‐IL‐17A) monoclonal IgG4 antibody, was demonstrated in moderate‐to‐severe psoriasis patients when administered via prefilled syringe (PFS).ObjectiveTo evaluate the effect of two drug delivery devices on the pharmacokinetics (PK) of ixekizumab as well as efficacy and safety with both devices.MethodsIn the first 12 weeks of an open‐label, phase 3 study, moderate‐to‐severe psoriasis patients were randomized to ixekizumab delivery via PFS or autoinjector device. Randomization was stratified by weight (<80 kg, 80–100 kg, >100 kg), injection assistance (yes/no) and injection site (arm, thigh or abdomen). Following a 160‐mg initial dose at week 0, patients received subcutaneous 80‐mg ixekizumab as a single injection every 2 weeks for 12 weeks. Blood samples were collected following the initial 160‐mg dose on days 2, 4, 7, 10 and 14 for PK analysis. Primary PK parameters were maximum concentration (C max) and area under the curve (AUC 0‐tlast) where t last is the time of last sample (14 days ± 24 h). Efficacy was assessed by percent improvement on the Psoriasis Area and Severity Index (PASI) at week 12. Adverse event reporting, vital signs and clinical laboratory data were used to evaluate safety.ResultsOf 204 randomized patients, 192 were included in the PK analysis (PFS: 94; autoinjector: 98). The PFS and autoinjector showed similar geometric mean C max (90% CI) [15.0 μg/mL (13.9–16.1) vs. 14.8 μg/mL (13.8–15.9)] and geometric mean AUC 0‐tlast (90% CI) [157 μg × day/mL (147–168) vs. 154 μg × day/mL (144–165)]. When comparing C max and AUC 0‐tlast of the autoinjector to PFS, the geometric LS mean ratios were 0.97. At week 12, mean percent PASI improvement (via modified baseline observation carried forward) was similar with the PFS (89.3%) and autoinjector (86.9%). Both devices had safety results that were consistent with the known safety profile of ixekizumab.ConclusionThe PK, efficacy and safety of ixekizumab administered subcutaneously by PFS and autoinjector were similar. Clinicaltrials.gov number: NCT01777191 https://clinicaltrials.gov/ct2/show/NCT01777191

Usability of a novel disposable autoinjector device for ixekizumab: results from a qualitative study and an open-label clinical trial, including patient-reported experience

“…The study design and primary results, including safety findings, for the UNCOVER-A trial were reported previously. 16 Briefly, in this randomized, open-label, Phase III study, patients with moderate-to-severe Ps were assigned by a computer-generated random sequence to an injection device (prefilled syringe or autoinjector). Patients received 80 mg ixekizumab as one subcutaneous injection every 2 weeks, following a 160 mg initial dose at week 0 (baseline visit; administered as two 80 mg injections).…”

“…The primary objective was to evaluate the pharmacokinetics of ixekizumab delivered via autoinjector or prefilled syringe. 16 A secondary objective was to evaluate the patient/caregiver experience with the autoinjector using the subcutaneous administration assessment questionnaire (SQAAQ). The SQAAQ is a novel, 12-item, self-administered questionnaire that assesses ease of use of the device and patient confidence while using the device to administer a subcutaneous injection of drug ( Table 3 ).…”

“… 14 , 15 In addition, the pharmacokinetic profile of ixekizumab is equivalent when delivered by autoinjector or prefilled syringe. 16 …”

Ixekizumab or secukinumab in psoriasis: what difference does it make?

“…Can the difference in efficacy between the two agents be explained by differences in pharmacokinetics? Table compares the basic pharmacokinetic and dosing characteristics of ixekizumab and secukinumab . Both drugs have similar bioavailability when given subcutaneously.…”

Role of IL-17 in plaque psoriasis: therapeutic potential of ixekizumab

“…In this open label study, patients were randomized to receive ixekizumab 80 mg every 2 weeks up until week 12 following a 160 mg initial dose at week 0. Primary parameters were Cmax (the maximum concentration) and time to reach Cmax (tmax), the results being ~15 μg/mL and 14.8 μg/mL for the prefilled syringe and the auto-injection devices, respectively, with both devices having a tmax of approximately 4 days 20,24…”