Phase III Study of Corabotase for Moderate to Severe Glabellar Lines in Adults

The primary objective is to evaluate the efficacy of a single intramuscular dose of IPN10200 versus placebo in improving the appearance of moderate to severe glabellar lines at Week 4 under maximum frown. Secondary objectives are to:

• In the double‑blind phase, assess efficacy of a single dose at each post‑treatment timepoint.
• Measure participant satisfaction with facial appearance at each post‑treatment visit.
• Evaluate changes in psychological function at each post‑treatment visit.
• Determine time to onset of treatment response.
• Determine duration of response.
• Assess safety and tolerability after a single dose.
• Detect anti‑IPN10200 antibodies after a single dose.
• In the open‑label phase, assess efficacy of repeat doses on the appearance of moderate to severe glabellar lines.
• Measure participant satisfaction with facial appearance after repeat dosing.
• Evaluate changes in psychological function after repeat dosing.
• Determine time to retreatment.
• Assess safety and tolerability after repeat dosing.
• Detect anti‑IPN10200 antibodies after repeat dosing.

The trial enrolled 1,070 adult participants, both male and female, who were at least 18 years of age and presented with moderate to severe glabellar lines at maximum frown as confirmed by validated photographic and categorical scales. All subjects were required to be dissatisfied with the appearance of their lines, capable of providing informed consent, and able to comply with study procedures; females had to use contraception in accordance with local regulations. Individuals residing in institutions, sponsor employees, study personnel, or immediate family members of staff were excluded, as were persons unable to give consent or to complete the study. No specific dietary, physical‑activity, or habit restrictions were imposed beyond the general health requirements for participation.

The study is a Phase III, multicentre, randomized, double-blind, placebo-controlled trial followed by an open‑label extension, designed to evaluate the efficacy and safety of a single intramuscular dose of IPN10200 (corabotase) for moderate to severe glabellar lines and the long‑term outcomes of repeat dosing. Participant involvement spans approximately 52 weeks, beginning with a screening visit to confirm eligibility criteria, followed by a baseline visit on Day 0 where the assigned intervention (IPN10200 or placebo) is administered. Subsequent scheduled assessments occur at Weeks 1, 2, 4, 12, 24, 36 and 52, each comprising investigator‑live assessment, subject self‑assessment, safety evaluations, and collection of immunogenicity data; the Week 4 visit serves as the primary efficacy time point. The open‑label phase permits retreatment cycles with similar follow‑up intervals, concluding with an end‑of‑study visit that finalizes efficacy, safety, and antibody analyses. Participants may be withdrawn prematurely (early termination) for reasons such as serious adverse events, emergence of contraindicating medical conditions, non‑compliance with protocol procedures, or voluntary withdrawal of consent. The primary efficacy outcome is a ≥2‑grade improvement to “None” or “Mild” on the Investigator’s Live Assessment (and Subject’s Self‑Assessment in North America) at Week 4; multiple secondary endpoints assess response durability, patient satisfaction, quality‑of‑life measures, and safety parameters throughout the trial duration.

The investigational product CORABOTASE is supplied as a solution for injection intended for intramuscular use. Each participant receives a single administration of 0.00 ng (nanograms) of the active substance, delivered via the intramuscular route. The formulation is provided in a ready‑to‑use injectable solution, and dosing is limited to one injection per treatment cycle.

The comparator arm utilizes a Placebo consisting of excipients formulated as a lyophilised powder for reconstitution into a solution for injection, also intended for intramuscular administration. No active pharmaceutical ingredient is present in the placebo preparation.

Both investigational and placebo products are administered as a single intramuscular injection at baseline. Subsequent repeat dosing may be performed in an open‑label extension, following the same administration parameters. Compliance with the dosing schedule is monitored by documentation of injection timing, verification of product accountability, and recording of any deviations in the case report form.

Efficacy will be evaluated using predefined clinical and patient‑reported endpoints. The primary endpoint is a multi‑component response defined as an improvement of at least two grades from baseline together with a rating of “None” or “Mild” at Week 4 on both the Investigator’s Live Assessment (ILA) and the Subject’s Self Assessment (SSA) at maximum frown (MF) for participants in North America, and an improvement of at least two grades on the ILA at MF for participants in the EU and the rest of the world. Secondary efficacy assessments include the following measurements at each post‑treatment visit (excluding specified weeks):

• Score of “None” or “Mild” on the ILA at MF.
• Score of “None” or “Mild” on the SSA at MF.
• Combined ILA and SSA response meeting the two‑grade improvement and “None”/“Mild” criteria.
• Two‑grade improvement on the ILA at MF.
• Two‑grade improvement on the SSA at MF.
• One‑grade improvement on the ILA at MF and at rest.
• One‑grade improvement on the SSA at MF.
• “Very Satisfied” or “Satisfied” response on the Subject‑Level Satisfaction (SLS) questionnaire.
• Change from baseline in the ageing appearance visual analogue scale (VAS) of the FACE‑Q scale.
• Improvement of at least 10 points from baseline on the Rasch Transformed Score of the FACE‑Q Psychological Function Scale.
• Time to onset of treatment response recorded in participant diaries (Days 1–8).
• Duration of response defined as the time until the ILA at MF returns to a “Moderate” or “Severe” grade.