Clostridium botulinum, neurotoxin serotype A/B (also listed as CORABOTASE / Modified recombinant botulinum neurotoxin serotype AB) for Glabellar frown lines | Forehead lines | Lateral canthal lines (crow's feet)

Inclusion criteria

• {"criterion_text":"- 1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.\n- 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.\n- 11. Participant has both the time and the ability to complete the study and comply with study instructions.\n- 12. Does not reside in an institution by administrative or court order.\n- 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.\n- 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.\n- 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.\n- 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).\n- 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).\n- 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.\n- 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.\n- 8. Dissatisfied or very dissatisfied (Grade 2 or 3) with their lines (Stages 1 to 3) at Baseline, as assessed by the SLS.\n- 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."}

Exclusion criteria

• {"criterion_text":"- 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).\n- 10. Any planned facial cosmetic surgery during the study.\n- 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.\n- 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.\n- 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.\n- 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.\n- 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\n- 16. An inability to substantially lessen GL and/or horizontal forehead rhytids even by physically spreading them apart as determined by the investigator.\n- 17. Known allergy or hypersensitivity to BoNT, or any excipients of IPN10200 or Dysport/Azzalure, or allergy to cow's milk protein.\n- 18. A history of drug or alcohol abuse.\n- 19. Pregnant women, nursing women, premenopausal women or women of childbearing potential not willing to practice a highly effective form of contraception method.\n- 2. A history of eyelid blepharoplasty or brow lift within the past 5 years\n- 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.\n- 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.\n- 3. A history of facial nerve palsy.\n- 4. Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin.\n- 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.)\n- 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)\n- 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.\n- 8. Any prior treatment with permanent fillers in the upper face including the GL, FHL and LCL area.\n- 9. Any prior treatment with long lasting dermal fillers or any permanent procedures 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."}

Primary endpoints

• {"endpoint_text":"- 1. Incidence of treatment emergent adverse events (TEAEs) at each dose At Stage 1/Step 1, Stage 3","definition_or_measurement_approach":"Incidence of TEAEs reported at each dose level; safety assessment in Stage 1/Step 1 and Stage 3."}
• {"endpoint_text":"- 2. Incidence of serious adverse events (SAEs) at each dose At Stage 1/Step 1, Stage 3","definition_or_measurement_approach":"Incidence of SAEs reported at each dose level; safety assessment in Stage 1/Step 1 and Stage 3."}
• {"endpoint_text":"- 3. Incidence of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs) At Stage 1/Step 1, Stage 3","definition_or_measurement_approach":"Number and incidence of AEs or SAEs leading to study withdrawal and AESIs, reported by dose and stage."}
• {"endpoint_text":"- 4. Response to treatment At Stage 2 for the FHL group.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:","definition_or_measurement_approach":"Composite response defined as ≥2-grade improvement on both ILA and SSA at maximum contraction on forehead lines; ILA uses a validated 4-point photographic scale; SSA uses a validated 4-point categorical scale."}
• {"endpoint_text":"- 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)s at maximum frown and at rest where 0 is “none” and 3 is “severe”","definition_or_measurement_approach":"ILA measurement: validated 4-point photographic scale (0 none to 3 severe) at maximum frown and at rest."}
• {"endpoint_text":"- 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: 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”","definition_or_measurement_approach":"SSA measurement: validated 4-point categorical patient-reported scale (0 no wrinkles to 3 severe) at maximum frown."}
• {"endpoint_text":"- 5. Response to treatment At Stage 2 for the glabellar lines (GL)+ FHL group. 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”","definition_or_measurement_approach":"Composite ≥2-grade improvement on ILA and SSA for GL+FHL; ILA defined as validated 4-point photographic scale (0–3)."}
• {"endpoint_text":"- 5. Response to treatment At Stage 2 for the glabellar lines (GL)+ FHL group. Measured by the composite response of ≥ 2-grade improvement on ILA and SSA at maximum contraction on the forehead lines (FHL) area: 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”","definition_or_measurement_approach":"SSA defined as validated 4-point categorical scale (0–3) assessing GLs and FHLs at maximum frown."}
• {"endpoint_text":"- 6. Response to treatment At stage 2 for the LCL group. 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”","definition_or_measurement_approach":"Composite ≥2-grade improvement on ILA and SSA for lateral canthal lines; ILA is validated 4-point photographic scale (0–3)."}
• {"endpoint_text":"- 6. Response to treatment At stage 2 for the LCL group. 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: 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”","definition_or_measurement_approach":"SSA is validated 4-point categorical scale (0–3) assessing LCLs at maximum frown."}
• {"endpoint_text":"- 7. Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs Double Blind phase. Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator.","definition_or_measurement_approach":"Proportion of participants with clinically significant changes from baseline in vital signs during the double-blind phase; clinical significance graded by investigator."}
• {"endpoint_text":"- 8. Percentage of participants with clinically significant Change from baseline in 12-lead Electrocardiogram (ECG) readings Double Blind phase.","definition_or_measurement_approach":"Proportion of participants with clinically significant changes from baseline in 12-lead ECG readings during double-blind phase."}
• {"endpoint_text":"- 9. Percentage of participants with clinically significant change from baseline in facial and focused neurological/physical examination. 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.","definition_or_measurement_approach":"Proportion of participants with clinically significant changes from baseline in facial and focused neurological/physical exams during double-blind phase; clinical significance graded by investigator."}

Secondary endpoints

• {"endpoint_text":"- 1.\tPercentage of participants response to treatment 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)","definition_or_measurement_approach":"Composite response ≥2-grade improvement on ILA and SSA for each facial area (GL/LCL/FHL) at each stage."}
• {"endpoint_text":"- 1. 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”","definition_or_measurement_approach":"ILA: validated 4-point photographic scale (0 none to 3 extremely pronounced) assessing severity at maximum frown and at rest."}
• {"endpoint_text":"- 1. 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) 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”","definition_or_measurement_approach":"SSA: validated 4-point categorical patient-reported scale (0 no wrinkles to 3 severe) at maximum frown."}
• {"endpoint_text":"- 2.\tPercentage of participants response to treatment as measured by the reduction of ≥1 grade on the ILA at maximum contraction for each concerned facial area For all stages.","definition_or_measurement_approach":"Proportion with ≥1-grade reduction on ILA at maximum contraction for each facial area, across stages."}
• {"endpoint_text":"- 3.\tPercentage of pa rticipants with clinically significant change from baseline in facial and focused neurological/physical examination. Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator.","definition_or_measurement_approach":"Proportion with clinically significant changes in facial and focused neurological/physical exam vs baseline; graded by investigator."}
• {"endpoint_text":"- 4.\tPercentage of participants response to treatment as achieved by a score of “none” or “mild” as measured by the ILA at rest For all stages.","definition_or_measurement_approach":"Proportion achieving ILA score of 'none' or 'mild' at rest for each stage."}
• {"endpoint_text":"- 5.\tPercentage of participants response to treatment as measured by the reduction of ≥1 grade on the SSA at maximum contraction for each concerned facial area For all stages","definition_or_measurement_approach":"Proportion with ≥1-grade reduction on SSA at maximum contraction for each facial area across stages."}
• {"endpoint_text":"- 6.\tPercentage 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. S","definition_or_measurement_approach":"Proportion achieving SSA score 'none' or 'mild' at maximum contraction for each facial area."}
• {"endpoint_text":"- 7.\tPercentage of participants response to treatment as achieved by a score of “very satisfied” or “satisfied” on the Subject Level of Satisfaction (SLS) for each concerned facial area. For all stages","definition_or_measurement_approach":"Proportion reporting 'very satisfied' or 'satisfied' on SLS for each facial area across stages."}
• {"endpoint_text":"- 8.\t Duration of treatment response based on ILA and SSA at maximum contraction for each concerned facial area. For all stages","definition_or_measurement_approach":"Duration of response determined from ILA and SSA at maximum contraction for each facial area."}
• {"endpoint_text":"- 9.\tTime to onset of treatment response based on subject diary cards to evaluate the appearance of their lines for each concerned facial area For all stages.","definition_or_measurement_approach":"Time to onset evaluated from subject diary cards reporting appearance of lines for each facial area."}
• {"endpoint_text":"- 10.\tSatisfaction with facial appearance, measured by Facial Appearance Overall scale score on the Face-Q satisfaction scale. Stage 3.","definition_or_measurement_approach":"Face-Q Facial Appearance Overall scale score (participant-reported) at Stage 3."}
• {"endpoint_text":"- 10. 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).","definition_or_measurement_approach":"Description of Face-Q instrument and domains used to measure participant-reported outcomes."}
• {"endpoint_text":"- 11.\tSatisfaction with facial appearance, measured by FACE-Q Short Form Facial Appearance scale score. 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.","definition_or_measurement_approach":"FACE-Q Short Form Facial Appearance participant-reported scale (very dissatisfied to very satisfied) at Stage 3."}
• {"endpoint_text":"- 12.\tIncidence, severity and nature of treatment emergent adverse events (TEAEs). All stages (except Stage 1/Step 1)","definition_or_measurement_approach":"Incidence, severity and nature of TEAEs reported for all stages except Stage 1/Step 1."}
• {"endpoint_text":"- 13.\tIncidence, severity and nature of serious adverse events (SAEs) All stages (except Stage 1/Step 1)","definition_or_measurement_approach":"Incidence, severity and nature of SAEs reported for all stages except Stage 1/Step 1."}
• {"endpoint_text":"- 14.\t Incidence, severity and nature of Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs) All stages (except Stage 1/Step 1)","definition_or_measurement_approach":"Incidence, severity and nature of AEs/SAEs leading to withdrawals and AESIs for all stages except Stage 1/Step 1."}
• {"endpoint_text":"- 15.\tPercentage of Participants With Clinically Significant Changes from baseline in Vital Signs. 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","definition_or_measurement_approach":"Proportion with clinically significant changes in vital signs from baseline for all stages except Stage 1/Step 1, graded by investigator."}
• {"endpoint_text":"- 16.\tTime between two consecutive injections. Stage 1/Step 3","definition_or_measurement_approach":"Interval (time) between two consecutive injections measured in Stage 1/Step 3."}
• {"endpoint_text":"- 17.\tPercentage of participants with binding antibodies to IPN10200 Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3","definition_or_measurement_approach":"Proportion of participants with binding antibodies to IPN10200 assessed in specified stages."}
• {"endpoint_text":"- 18.\tPercentage of participants with neutralising antibodies to IPN10200 Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3","definition_or_measurement_approach":"Proportion of participants with neutralising antibodies to IPN10200 assessed in specified stages."}
• {"endpoint_text":"- 19.\tPercentage of participants with binding antibodies to BontA Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3","definition_or_measurement_approach":"Proportion with binding antibodies to BoNT/A assessed in specified stages."}
• {"endpoint_text":"- 20.\tPercentage of participants with neutralising antibodies to BontA Stage 1/Step 2, Stage 1/Step 3, Stage 2, and Stage 3","definition_or_measurement_approach":"Proportion with neutralising antibodies to BoNT/A assessed in specified stages."}

Germany

Earliest CTIS Part Ii Submission Date

20-05-2024

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

714

Number Of Sites

6

Number Of Participants

508

France

Earliest CTIS Part Ii Submission Date

20-05-2024

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

690

Number Of Sites

3

Number Of Participants

263

Primary sponsor

Full Name

Ipsen Innovation

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Multiple sponsorDuties including labs and medical monitoring, review and evaluation of information relevant to the safety of the drug; other duties (codes 1,12,2,8) as listed in CTIS record

Name

Biotrial

Responsibilities

Sponsor duties codes 10 and 6 listed in CTIS record

Name

Meeting Protocol Worldwide LP

Responsibilities

Patient reimbursement (France)

Name

Cognizant Worldwide Limited

Responsibilities

PV case processing

Name

S-Clinica

Responsibilities

IVRS – treatment randomisation

Third parties

• {"country":"Belgium","full_name":"S-Clinica","duties_or_roles":"IVRS – treatment randomisation (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 1, 12, 15 (Labs and medical monitoring, review and evaluation of information relevant to the safety of the drug), 2, 8","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Biotrial","duties_or_roles":"sponsorDuties codes: 10, 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Meeting Protocol Worldwide LP","duties_or_roles":"Patient reimbursement (France) (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Cognizant Worldwide Limited","duties_or_roles":"PV case processing (sponsorDuties code 15)","organisation_type":"Non-Pharmaceutical company"}