A Study to Assess the Safety and Efficacy of IPN10200 in Adult Participants With Moderate to Severe Upper Facial Lines

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy profile of increasing doses of IPN10200 in comparison to placebo, with the aim to discover the doses(s) that offer the best efficacy/safety profile when used for the treatment of moderate to severe Upper Facial Lines. This study will be conducted in three stages. The full study (including all stages) will have a maximum 448 participants. The protocol is currently approved up to stage 1, step 1 and stage 1/ step 2. Stage 1 (phase Ib & II) Step 1 (Phase Ib): a dose-escalation first-in-human step in participants with moderate to severe Glabellar Lines (GL) Step 2 (Phase II): dose finding step in participants with moderate to severe GL as compared with Dysport Stage 2 (phase II) - An evaluation of efficacy and safety of IPN10200 in one of the following regions: GL + forehead lines (FHL) or lateral canthal lines (LCL) Stage 3 (phase II) - A safety and efficacy evaluation of IPN10200 in all three regions (GL, FHL and LCL)

Official Title
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A Phase Ib/II, Multicentre, Double-blind, Randomised, Placebo-controlled, Dose Escalation and Dose-finding Study to Evaluate the Safety and Efficacy of IPN10200 in Improving the Appearance of Moderate to Severe Upper Facial Lines in Adults

Conditions
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Moderate to Severe Upper Facial Lines

Intervention / Treatment
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* Biological: IPN10200
* Biological: IPN10200 Placebo
* Biological: Dysport


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent. Moderate or severe (Grade 2 or 3) GL at maximum contraction at Baseline, as assessed by the ILA using a validated 4-point photographic scale. Moderate or severe (Grade 2 or 3) GL at maximum contraction at Baseline, as assessed by the SSA using a validated 4-point categorical scale. Dissatisfied or very dissatisfied (Grade 2 or 3) with their lines at Baseline, as assessed by the SLS. Exclusion Criteria: An active infection or other skin problems in the upper face including the GL, FHL, and LCL area (e.g. acute acne lesions or ulcers). A history of eyelid blepharoplasty or brow lift within the past 5 years A history of facial nerve palsy. Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin. Any known medical condition that may put the participant at increased risk in regard to exposure to BoNT of any serotype (i.e. myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, etc.) Has COVID-19 illness or a positive SARS-CoV-2 test, or the presence of any other condition (e.g. neuromuscular disorder or other disorder that could interfere with neuromuscular function) Previous treatment with any BoNT serotype for Stage 1 / Step 1 or any recent reatment (within the past 6 months prior to baseline) with any BoNT serotype for Stage 1 / Step 2. Any prior treatment with permanent fillers in the upper face including the GL, FHL and LCL area. Any prior treatment with long lasting dermal fillers in the upper face including the GL area within the past 3 years and/or skin abrasions/resurfacing (whatever the interventional technic used) within the past 5 years, or photo rejuvenation or skin/vascular laser intervention within the 12 months prior to Baseline. Any planned facial cosmetic surgery during the study. Use of concomitant therapy which, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study intervention, including medications affecting bleeding disorders (e.g. antiplatelet agents and/or anticoagulants given for treatment or prevention of cardiovascular/cerebrovascular diseases). Use of medications that affect neuromuscular transmission, such as curare-like non depolarising agents, lincosamides, polymyxins, anticholinesterases and aminoglycoside antibiotics, within the past 30 days prior to Baseline. Use of any experimental device within 30 days or use of any treatment with an experimental drug within five times the documented terminal half-life of the respective drug or its metabolites or if the halflife is unknown within 30 days prior to the start of the study (prior to Baseline) and during the conduct of the study. Known positive for hepatitis B antigen, or hepatitis C virus antibody, or for human immunodeficiency virus (HIV) or a diagnosis of acquired immunodeficiency syndrome. Clinically diagnosed significant anxiety disorder, or any other significant psychiatric disorder (e.g. depression) that might interfere with the participant's participation in the study An inability to substantially lessen GL and/or horizontal forehead rhytids even by physically spreading them apart as determined by the investigator. Known allergy or hypersensitivity to BoNT or any excipients of IPN10200 or Dusport/Azzalure, or allergy to cow's milk protein. A history of drug or alcohol abuse Pregnant women, nursing women, premenopausal women or women of childbearing potential not willing to practice a highly effective form of contraception method Male participants who are not vasectomized and who have female partners of childbearing potential and are not willing to use condoms with spermicide throughout study participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPN10200 group<br>Several cohorts of participants will be randomized in a ratio of 3:1 in a dose-escalation manner. The decision to escalate to the next dose for each cohort will be based on Data Monitoring Committee recommendation. | Biological: IPN10200<br>* Several different doses will be administrated in a dose-escalation manner. One single injection will be injected locally into several sites across the glabellar region.<br>|
| Placebo Comparator: Placebo group<br>Several cohorts of participants will be randomized in a ratio of 3:1 in a dose-escalation manner. The decision to escalate to the next dose for each cohort will be based on Data Monitoring Committee recommendation. | Biological: IPN10200 Placebo<br>* One single injection of study intervention will be injected locally into several sites across the glabellar region.<br>|
| Active Comparator: Dysport group (stage 1 / step 2 only)<br> | Biological: Dysport<br>* Single administration of study intervention in stage 1 / step 2 only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (TEAEs) at each dose |  | From the baseline to the end of the study (9 months) | 
| Incidence of serious adverse events (SAEs) at each dose |  | From the baseline to the end of the study (9 months) | 
| Incidence of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs) |  | From the baseline to the end of the study (9 months) | 
| Response to treatment as measured by the composite response of 2-grade improvement on Investigator's Live Assessment (ILA) at maximum contraction | ILA: a validated 4-point photographic scale to assess the severity and appearance of the GLs at maximum frown and at rest where 0 is no lines are noticeable and 3 is lines are extremely pronounced | At Week 4 | 
| Response to treatment as measured by the composite response of 2-grade improvement on subject's self-assessment (SSA) at maximum contraction | SSA: a validated 4-point categorical scale to assess the appearance of their Glabellar Lines (GLs) at maximum frown where 0 is no wrinkles and 3 is severe wrinkles. | At Week 4 | 
| Response to treatment as measured by the composite response of 2-grade improvement on ILA at maximum contraction on the forehead lines (FHL) area | At Stage 2 for the glabellar lines (GL)+ FHL group | At Week 4 | 
| Response to treatment as measured by the composite response of 2-grade improvement on SSA at maximum contraction on the forehead lines (FHL) area | At Stage 2 for the glabellar lines (GL)+ FHL group | At Week 4 | 
| Response to treatment as measured by the composite response of 2-grade improvement ILA at maximum contraction on the lateral canthal lines (LCL) area | At stage 2 for the LCL group | At Week 4 | 
| Response to treatment as measured by the composite response of 2-grade improvement on SSA at maximum contraction on the LCL area | At stage 2 for the LCL group | At Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment measured by the composite response of 2-grade improvement on ILA | For all stages. ILA: a validated 4-point photographic scale to assess the severity and appearance of the GLs at maximum frown and at rest where 0 is no lines are noticeable and 3 is lines are extremely pronounced | From the baseline to the end of the study (9 months) | 
| Response to treatment measured by the composite response of 2-grade improvement on SSA | For all stages. SSA: a validated 4-point categorical scale to assess the appearance of their Glabellar Lines (GLs) at maximum frown where 0 is no wrinkles and 3 is severe wrinkles. | From the baseline to the end of the study (9 months) | 
| Response to treatment as measured by the reduction of ≥2 grades on the ILA at maximum contraction |  | From the baseline to the end of the study (9 months) | 
| Response to treatment as achieved by a score of none or mild as measured by the ILA at maximum contraction |  | From the baseline to the end of the study (9 months) | 
| Response to treatment as achieved by a score of none or mild as measured by the ILA at rest |  | From the baseline to the end of the study (9 months) | 
| Response to treatment as measured by the reduction of ≥2 grades on the SSA at maximum contraction |  | From the baseline to the end of the study (9 months) | 
| Response to treatment as achieved by a score of none or mild as measured by the SSA at maximum contraction |  | From the baseline to the end of the study (9 months) | 
| Response to treatment as achieved by a score of very satisfied or satisfied on the Subject Level of Satisfaction (SLS) |  | From the baseline to the end of the study (9 months) | 
| Duration of treatment response based on ILA and SSA at maximum contraction |  | From the baseline to the end of the study (9 months) | 
| Time to onset of treatment response based on subject diary cards to evaluate the appearance of their lines |  | From the baseline to the end of the study (9 months) | 
| Satisfaction with facial appearance scale score on the Face-Q satisfaction scale | Face Q is a participant-reported outcome instrument to evaluate the experience and outcomes of aesthetic facial procedures from the participant's perspective. The Face Q is composed of over 40 scales, covering four domains (Satisfaction with Facial Appearance, Health Related Quality of Life, Adverse Effects, and Process of Care). | From the baseline to the end of the study (9 months) | 
| Incidence, severity and nature of treatment emergent adverse events (TEAEs) |  | From baseline to the end of the study (9 months) | 
| Incidence, severity and nature of serious adverse events (SAEs) |  | From baseline to the end of the study (9 months) | 
| Incidence, severity and nature of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs) |  | From baseline to the end of the study (9 months) | 
| Presence of IPN10200 antibodies and titres (binding and neutralizing) |  | At Week 4 , Week 24 and Week 36 | 
| Presence of BoNT-A antibodies and titres (binding and neutralizing) |  | At Week 4 , Week 24 and Week 36 |