P1112 Pharmacokinetic comparability and safety between original and citrate-free mirikizumab formulations for subcutaneous injections: Results from three clinical trials in healthy participants
Bibliographic record
Abstract
Abstract 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".