Dataset Information

Ixekizumab Citrate-Free Formulation: Results from Two Clinical Trials.

ABSTRACT:

Introduction

Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A.

Methods

Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensity on injection as measured by visual analog scale of pain (VAS) scores. Subjects (N = 70) were randomized 1:1:1 at the beginning to three possible treatment sequences and received a 1 mL SC injection of the three formulations sequentially in the abdomen on days 1, 8, and 15, respectively. A mixed-effects repeated measures analysis model was used to analyze VAS score by time post-injection. Study B (NCT04259346) evaluated the bioequivalence of a single 80 mg dose of CF formulation compared to the original commercial formulation. Subjects (N = 245) were randomized 1:1 to either commercial or CF formulation and received a single SC injection into the abdomen, arm, or thigh.

Results

Primary endpoint was achieved in both studies. In study A, least-squares mean (LSM) difference of VAS scores immediately post injection between commercial (n = 61) and CF formulation (n = 63) was - 21.7 (p < 0.0001), indicating a lower degree of pain associated with CF formulation. In study B, bioequivalence of the CF formulation was established as 90% CIs for the ratio of geometric LSM AUC_0-tlast, AUC_0-∞, and C_max between treatments were contained within the prespecified limits of 0.8 and 1.25. Except for less ISP in the CF formulation, overall safety profile was comparable.

Conclusion

Ixekizumab CF formulation proved to be bioequivalent, was associated with less ISP, and had no other notable differences in the safety profile compared to the original commercial formulation.

Trail registration

ClinicalTrials.gov identifier NCT03848403, NCT04259346.

SUBMITTER: Chabra S

PROVIDER: S-EPMC9022732 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Ixekizumab Citrate-Free Formulation: Results from Two Clinical Trials.

Chabra Sanjay S Gill B J BJ Gallo Gaia G Zhu Danting D Pitou Celine C Payne Christopher D CD Accioly Ana A Puig Luis L

Advances in therapy 20220421 6

<h4>Introduction</h4>Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A.<h4>Methods</h4>Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensi ...[more]

PMID: 35449322

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Project description:IntroductionDifferences in psoriatic arthritis (PsA) treatment response between sexes for ixekizumab, an interleukin-17A antagonist, are largely unexplored. This analysis used data from randomized clinical trials (RCTs) evaluating ixekizumab to study differences in treatment response between male and female patients with PsA.MethodsWe used pooled data from patients enrolled in SPIRIT-P1 and SPIRIT-P2 (NCT01695239 and NCT02349295, respectively), phase 3 RCTs evaluating ixekizumab every 4 and 2 weeks in patients with active PsA. Subgroups of patients were defined by sex (male, female). Efficacy was measured by the proportion of male and female patients achieving American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70), minimal disease activity or very low disease activity (MDA/VLDA), and Disease Activity Index for Psoriatic Arthritis (DAPSA) scores representing low disease activity (LDA) or remission through week 156. Changes from baseline in components of the above measures were also assessed through week 156.ResultsCompared to male patients at baseline, female patients were older, had higher body mass index and lower C-reactive protein levels, and had worse tender joint count, Health Assessment Questionnaire Disability Index, and Leeds Enthesitis Index scores. Through week 156, female patients in all treatment arms had lower response rates than male patients in all analyzed composite measures (ACR20/50/70; MDA/VLDA; DAPSA LDA/remission), with significant differences observed at multiple timepoints in both ixekizumab treatment arms. Female patients also had smaller numeric changes from baseline in the composite measures' individual components.ConclusionCompared to female patients, male patients had greater response rates in ACR20/50/70, MDA/VLDA, and DAPSA LDA/remission and numerically larger improvements in these measures' individual components, although clinical significance is unclear. Continued efforts to understand sex differences in treatment response may provide insights that can help optimize clinical decision making.Trial registrationClinicalTrials.gov identifiers, NCT01695239 and NCT02349295.

Project description:ObjectiveTo evaluate ixekizumab safety in adults with psoriatic arthritis (PsA).MethodsSafety data from 2 integrated data sets are presented: 1) 24-week, double-blind, placebo-controlled period of SPIRIT-P1 and SPIRIT-P2; and 2) all ixekizumab-treated patients of SPIRIT-P1 and SPIRIT-P2 plus SPIRIT-P3 open-label period. We report adverse event (AE) frequency and exposure-adjusted incidence rates per 100 patient-years at 12-week intervals to week 96.ResultsThe placebo-controlled period had 678 patients (safety population): 224 placebo, 229 ixekizumab every 4 weeks, and 225 ixekizumab every 2 weeks. Overall, 1,118 patients received ixekizumab (total exposure 1,373.4 patient-years). In the placebo-controlled period, the frequencies of ixekizumab-treated patients experiencing ≥1 treatment-emergent AE (TEAE) and those experiencing serious AEs were 68.1% (56.7% placebo) and 4.4% (2.7% placebo), respectively. Injection site reactions (ISRs) were very common (21.4% ixekizumab [4.5% placebo]), with ISR discontinuation rates of 1.1% (ixekizumab) and 0.4% (placebo). Through week 96, the incidence rates of ISRs decreased with increasing ixekizumab exposure. The frequencies of AEs of special interest were 32.8% (ixekizumab) and 27.7% (placebo); for serious infections, the frequencies were 1.3% and 0%, respectively; Candida infections, 2.6% and 0.4%; confirmed major adverse cardiac events, 0% and 0%; malignancy, 0.4% and 0%; hypersensitivities, 5.3% and 1.8%; and depression-related, 1.8% and 1.3%. The frequency of Crohn's disease and ulcerative colitis (investigator-reported) was 0% in both groups, and the frequencies of sponsor-determined inflammatory bowel disease were 0.2% in the ixekizumab group and 0% in the placebo group. Overall, no active tuberculosis, invasive Candida infections, anaphylaxis, or suicide/self-injury behaviors were reported.ConclusionThe PsA ixekizumab safety integrated data set reached 1,373.4 patient-years total exposure. Ixekizumab-treated patients had higher rates of overall TEAEs, serious infections, mucocutaneous Candida, hypersensitivities (non-anaphylactic), and ISRs than placebo-treated patients. No unexpected safety outcomes were reported.

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Dataset Information

Ixekizumab Citrate-Free Formulation: Results from Two Clinical Trials.

Introduction

Methods

Results

Conclusion

Trail registration

Publications

Ixekizumab Citrate-Free Formulation: Results from Two Clinical Trials.

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