Moderate to Severe Upper Facial Lines
Conditions
Brief summary
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 727 participants. 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 ranging step in participants with moderate to severe GL as compared with Dysport * Step 3 (Phase II): dose finding step in participants with moderate to severe GL as compared with Dysport, followed by an open label (OL) phase for the highest dose cohort to assess the long-term safety and efficacy of IPN10200. In the OL phase, participants may receive repeat administrations of IPN10200 for up to three additional cycles (up to four treatment cycles in total during the study). Stage 2 (phase II) - An evaluation of efficacy and safety of IPN10200 in one of the following regions: GL + forehead lines (FHL), 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)
Interventions
BIOLOGICALIPN10200
Stage 1: 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. Stage 2: One single injection will be injected locally into several sites across the glabellar, forehead and lateral Canthal regions. Stage 3: One single injection will be injected locally into several sites across the upper facial area.
BIOLOGICALIPN10200 Placebo
Stage 1: One single injection of study intervention will be injected locally into several sites across the glabellar region. Stage 2: One single injection will be injected locally into several sites across the glabellar, forehead and lateral Canthal regions. Stage 3: One single injection will be injected locally into several sites across the upper facial area.
BIOLOGICALDysport
Single administration of study intervention in stage 1 / step 2 and 3 only
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent. 2. Moderate or severe (Grade 2 or 3) GL (Stage 1) at maximum contraction at Baseline, as assessed by the ILA using a validated 4-point photographic scale. 3. Moderate or severe (Grade 2 or 3) GL (Stage 1) at maximum contraction at Baseline, as assessed by the SSA using a validated 4-point categorical scale. 4. Moderate or severe (Grade 2 or 3) FHL (Stage 2) at maximum contraction and moderate to severe GL at maximum contraction at Baseline or moderate to severe (Grade 2 or 3) LCL (Stage 2) at maximum contraction (Stage as assessed by the ILA using a 4-point photographic scale). 5. Moderate or severe (Grade 2 or 3) FHL (Stage 3) at maximum contraction and moderate to severe GL at maximum contraction at Baseline and moderate to severe (Grade 2 or 3) LCL (Stage 3) at maximum contraction (Stage as assessed by the ILA using a 4-point photographic scale). 6. Moderate or severe (Grade 2 or 3) FHL (Stage 2) at maximum contraction and moderate to severe GL maximum contraction at Baseline or moderate to severe (Grade 2 or 3) LCL (Stage 2) at maximum contraction as assessed by the SSA using a 4-point photographic scale. 7. Moderate or severe (Grade 2 or 3) FHL (Stage 3) at maximum contraction and moderate to severe GL maximum contraction at Baseline and moderate to severe (Grade 2 or 3) LCL (Stage 3) at maximum contraction, as assessed by the SSA using a 4-point photographic scale. 8. Dissatisfied or very dissatisfied (Grade 2 or 3) with their lines (Stages 1 to 3) at Baseline, as assessed by the SLS. 9. Male and female participants (only female for Stage 1/Step 1). Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 10. Capable of giving signed informed consent includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 11. Participant has both the time and the ability to complete the study and comply with study instructions. 12. Does not reside in an institution by administrative or court order. 13. Is not a sponsor employee or clinical research unit personnel directly affiliated with the study or is not an immediate family member. Immediate family is defined as a spouse, parent, child or sibling whether biological or legally adopted.
Exclusion criteria
1. 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). 2. A history of eyelid blepharoplasty or brow lift within the past 5 years 3. A history of facial nerve palsy. 4. Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin. 5. 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.) 6. Has COVID-19 illness or a known positive SARS-CoV-2 test (Stage 1), or the presence of any other condition (e.g. neuromuscular disorder or other disorder that could interfere with neuromuscular function) 7. Previous treatment with any BoNT serotype for Stage 1 / Step 1 or any recent treatment (within the past 9 months prior to baseline) with any BoNT serotype for Stage 1 / Step 2, Stage 1/Step 3, Stages 2 and 3. Participants treated in earlier Stages/Steps of the study must not be included in any later Stages/Steps. 8. Any prior treatment with permanent fillers in the upper face including the GL, FHL and LCL area. 9. Any prior treatment with long lasting dermal fillers or any permanent procedures in the upper face inclusion 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. 10. Any planned facial cosmetic surgery during the study. 11. Use of concomitant therapy which, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study intervention. Therapy considered necessary for the participant's welfare may be given at the discretion of the investigator. 12. Use of medications that affect neuromuscular transmission, such as curare-like non depolarising agents, lincosamides, polymyxins, anticholinesterases, aminoglycoside antibiotics and systemic retinoids, within the past 30 days prior to baseline are prohibited or a longer washout period of at least five half-lives might be required, as deemed appropriate by the investigator for longer-acting medications. Topical use of for example aminoglycoside medications or topical retinoids on the face apart from the area of injection would be acceptable. 13. 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. 14. Known positive for hepatitis B antigen, or hepatitis C virus antibody, or for human immunodeficiency virus (HIV) or a diagnosis of acquired immunodeficiency syndrome. 15. 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 16. An inability to substantially lessen GL and/or horizontal forehead rhytids even by physically spreading them apart as determined by the investigator. 17. Known allergy or hypersensitivity to BoNT or any excipients of IPN10200 or Dusport/Azzalure, or allergy to cow's milk protein. 18. A history of drug or alcohol abuse 19. Pregnant women, nursing women, premenopausal women or women of childbearing potential not willing to practice a highly effective form of contraception method 20. 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. 21. Any uncontrolled systemic disease or other significant medical condition which would be harmful for the participant to be entered into the study or continue participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment emergent adverse events (TEAEs) at each dose | From the baseline to the end of the study (9 months) | At Stage 1/Step 1, Stage 3 |
| Incidence of serious adverse events (SAEs) at each dose | From the baseline to the end of the study (9 months) | At Stage 1/Step 1, Stage 3 |
| 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) | At Stage 1/Step 1, Stage 3 |
| Response to treatment at Stage 2 for the FHL group | At Week 4 | Measured by the composite response of ≥ 2-grade improvement on Investigator's Live Assessment (ILA) and subject's self-assessment (SSA) at maximum contraction on the forehead lines: ILA: a validated 4-point photographic scale to assess the severity and appearance of the Forehead Lines (FHL) at maximum frown and at rest where 0 is "none" and 3 is "severe" SSA: a validated 4-point categorical scale to assess the appearance of their FHLs at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles" |
| Response to treatment at Stage 2 for the glabellar lines (GL)+ FHL group | At Week 4 | Measured by the composite response of ≥ 2-grade improvement on ILA and SSA at maximum contraction on the forehead lines (FHL) area: ILA: a validated 4-point photographic scale to assess the severity and appearance of the GLs and FHLs at maximum frown and at rest where 0 is "none" and 3 is "severe" SSA: a validated 4-point categorical scale to assess the appearance of their GLs and FHLs at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles" |
| Response to treatment at Stage 2 for the LCL group | At Week 4 | Measured by the composite response of ≥ 2-grade improvement ILA and SSA at maximum contraction on both sides of the lateral canthal lines (LCL) area: ILA: a validated 4-point photographic scale to assess the severity and appearance of the LCLs at maximum frown and at rest where 0 is "none" and 3 is "severe" SSA: a validated 4-point categorical scale to assess the appearance of their LCLs at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles" |
| Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs | From the baseline to the end of the study (6 years, 5 months) | Double Blind phase. Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator. |
| Percentage of participants with clinically significant Change from baseline in 12-lead Electrocardiogram (ECG) readings | From the baseline to the end of the study (6 years, 5 months) | Double Blind phase. |
| Percentage of participants with clinically significant change from baseline in facial and focused neurological/physical examination. | From the baseline to the end of the study (6 years, 5 months) | Double Blind phase. Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants response to treatment. | From the baseline to the end of the study (up to 6 years, 5 months) | For all stages. Measured by the composite response of ≥ 2-grade improvement on ILA and SSA for each concerned facial area in each respective stage (GL/LCL/FHL) ILA: a validated 4-point photographic scale to assess the severity and appearance of the GLs/LCLs/FHLs in each respective stage at maximum frown and at rest where 0 is "no lines are noticeable" and 3 is "lines are extremely pronounced" SSA: a validated 4-point categorical scale to assess the appearance of their GLs/LCLs/FHLs in each respective stage at maximum frown where 0 is "no wrinkles" and 3 is "severe wrinkles" |
| Percentage of participants response to treatment as measured by the reduction of ≥1 grade on the ILA at maximum contraction for each concerned facial area | From the baseline to the end of the study (up to 6 years, 5 months) | For all stages. |
| Percentage of participants with clinically significant change from baseline in facial and focused neurological/physical examination | From the baseline to the end of the study (up to 6 years, 5 months) | For all stages. Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator. |
| Percentage of participants response to treatment as achieved by a score of "none" or "mild" as measured by the ILA at rest on each facial area | From the baseline to the end of the study (up to 6 years, 5 months) | For all stages |
| Percentage of participants response to treatment as measured by the reduction of ≥1 grade on the SSA at maximum contraction for each concerned facial area | From the baseline to the end of the study (up to 6 years, 5 months) | For all stages. |
| Percentage of participants response to treatment as achieved by a score of "none" or "mild" as measured by the SSA at maximum contraction for each concerned facial area. | From the baseline to the end of the study (up to 6 years, 5 months) | Stage 2 and Stage 3. |
| Duration of treatment response based on ILA and SSA at maximum contraction for each concerned facial area | From the baseline to the end of the study (up to 6 years, 5 months) | For all stages. |
| 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) | — |
| Time to onset of treatment response based on subject diary cards to evaluate the appearance of their lines for each concerned facial area | From the baseline to the end of the study (up to 6 years, 5 months) | For all stages. |
| Satisfaction with facial appearance, measured by Facial Appearance Overall scale score on the Face-Q satisfaction scale | From the baseline to the end of the study (up to 6 years, 5 months) | Stage 3. 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 instrument is composed of over 40 scales, covering four domains (Satisfaction with Facial Appearance, Health Related Quality of Life, Adverse Effects, and Process of Care). |
| Satisfaction with facial appearance, measured by FACE-Q Short Form Facial Appearance scale score. | From the baseline to the end of the study (6 years, 5 months) | Stage 3. The FACE-Q Short Form Facial Appearance scale is a participant-reported outcome instrument. It asks how dissatisfied or satisfied the participant is with their upper facial lines (UFL) (GL+FHL+LCL). The scale ranges from very dissatisfied to very satisfied. |
| Incidence, severity and nature of treatment emergent adverse events (TEAEs) | From baseline to the end of the study (up to 6 years, 5 months) | All stages (except Stage 1/Step 1) |
| Incidence, severity and nature of serious adverse events (SAEs) | From baseline to the end of the study (up to 6 years, 5 months) | All stages (except Stage 1/Step 1) |
| 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 (up to 6 years, 5 months) | All stages (except Stage 1/Step 1) |
| Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs | From baseline to the end of the study (6 years, 5 months) | All stages (except Stage 1/Step 1). Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator. |
| Time between two consecutive injections | From baseline to the end of the study (up to 6 years, 5 months) | Stage 1/Step 3 . |
| Percentage of participants with binding antibodies to IPN10200 | At Week 4 , Week 24 and Week 36 | Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3 |
| Percentage of participants with neutralising antibodies to IPN10200 | At Week 4 , Week 24 and Week 36 | Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3 |
| Percentage of participants with binding antibodies to BontA | At Week 4 , Week 24 and Week 36 | Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3 |
| Percentage of participants with neutralising antibodies to BontA | At Week 4 , Week 24 and Week 36 | Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3 |
Countries
France, Germany
Contacts
STUDY_DIRECTORIpsen Medical Director
Ipsen
Outcome results
None listed