P1112 Pharmacokinetic comparability and safety between original and citrate-free mirikizumab formulations for subcutaneous injections: Results from three clinical trials in healthy participants
Authors: Otani Y , Feagan B , D’Haens G , Escobar R , Morris N , Payne C , Ugolini Lopes M , Zhang X 
Published: January 2025

Background

Mirikizumab (miri), a humanized IgG4 monoclonal antibody which selectively binds to the p19 subunit of human IL-23, is administered via subcutaneous (SC) injection. Since injection site pain (ISP) may be negatively affected by formulation buffer excipients such as citrate1, a citrate-free (CF) formulation of miri has been developed. We assessed the bioequivalence, ISP, and overall safety of the CF formulation of miri.

Methods

Three phase 1, two-arm, randomised, single-dose, subject-blind, parallel design studies were conducted in healthy subjects: one pilot relative bioavailability (RBA) study A (NCT04548219), and two bioequivalence (BE) studies B (NCT05515601) and C (NCT05644353). Subjects were randomised 1:1 to CF or original miri in all studies.

The primary endpoint in all studies was to assess the comparability between CF and original formulations via Cmax, area under the concentration versus time curve (AUC) (0-∞), and AUC(0-tlast). Study A assessed the RBA of a single 200 mg SC dose, Study B assessed the BE of a single 200 mg SC dose, and Study C assessed the BE of a single 300 mg SC dose. The 200 mg and 300 mg doses are proposed for ulcerative colitis and Crohn’s disease, respectively.

The secondary endpoint was safety assessment by spontaneous treatment-emergent adverse events and serious adverse events. In addition, in Study A, ISP was also quantified prospectively using the 100-mm validated visual analogue scale (VAS) assessment form2. Injection site reactions (ISRs) were prospectively assessed in Study A.

Results

The number of subjects who received miri were 60 in Study A, 396 in Study B, and 450 in Study C. Baseline characteristics were similar across studies and treatment groups.

There was no statistically significant difference in exposure between the formulations in Study A. Figure 1 shows that the CF formulation demonstrated BE in Studies B and C, with the 90% confidence intervals (CIs) of the ratios of geometric least squares means (LSM) within the pre-specified equivalence limits.

Figure 2 shows a statistically significant difference of 13.43 in the VAS Pain Score LSM at 1-minute post-dose for Study A, which is also considered clinically relevant3. Overall, CF and original miri demonstrated an acceptable safety profile consistent with previous work in healthy participants.

Conclusion

The CF formulation of mirikizumab is bioequivalent to the original formulation and is associated with a lower VAS pain score which may positively affect treatment experience.

References

1.Shi GH, Pisupati K, Parker JG, et al. Subcutaneous Injection Site Pain of Formulation Matrices. Pharm Res. 2021;38:779-793.

2.Williamson A and Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin Nurs. 2005;14(7):798-804.

3.Myles PS, Myles DB, Galagher W, et al. Measuring acute postoperative pain using the visual analog scale: the minimal clinically important difference and patient acceptable symptom state. Br J Anaesth. 2017;118(3):424-429.