Treatment of Moderate to Severe Upper Facial Lines MedDRA version: 21.1 Level: LLT Classification code 10052609 Term: Glabellar frown lines System Organ Class: 100000004858 MedDRA version: 21.1 Level: LLT Classification code 10052610 Term: Frown lines System Organ Class: 100000004858
Conditions
Interventions
Product Code: IPN59011
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Modified recombinant botulinum neurotoxin serotype A (mrBoNT-A)
Current Sponsor code: IPN
Sponsors
Ipsen Innovation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must fulfil all the following criteria to be included in the study: (1) Provision of written informed consent prior to any study related procedures. (2) Female and male subjects between 18 and 65 years of age, inclusive (for dose escalation, females only) (3) 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. (4) 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. (5) Moderate or severe (Grade 2 or 3) FHL at maximum contraction and moderate to severe GL at maximum contraction at Baseline or moderate to severe (Grade 2 or 3) LCL at maximum contraction (Stage as assessed by the ILA using a validated 4-point photographic scale). (6) Moderate or severe (Grade 2 or 3) FHL at maximum contraction and moderate to severe GL at maximum contraction at Baseline and moderate to severe (Grade 2 or 3) LCL at maximum contraction (Stage as assessed by the ILA using a validated 4-point photographic scale). (7) Moderate or severe (Grade 2 or 3) FHL at maximum contraction and moderate to severe GL maximum contraction at Baseline or moderate to severe (Grade 2 or 3) LCL at maximum contraction, as assessed by the SSA using a validated 4-point categorical scale. (8) Moderate or severe (Grade 2 or 3) FHL at maximum contraction and moderate to severe GL maximum contraction at Baseline and moderate to severe (Grade 2 or 3) LCL at maximum contraction, as assessed by the SSA using a validated 4-point categorical scale. (9) Dissatisfied or very dissatisfied (Grade 2 or 3) with their lines at Baseline, as assessed by the subject’s level of satisfaction. (10) A negative pregnancy test (for females of childbearing potential only). Non-childbearing potential is defined as postmenopausal for at least 1 year; surgical sterilisation at least 3 months before entering the study; or hysterectomy. (11) Subject has both the time and the ability to complete the study and comply with study instructions. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 374 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study if they meet any of the following criteria: (1) Previous treatment with any BTX serotype (for dose escalation) or any recent treatment (within the past 6 months prior to Baseline) with any BTX serotype. (2) Any prior treatment with permanent fillers in the upper face including the GL, FHL and LCL area. (3) 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. (4) Any planned facial cosmetic surgery during the study. (5) A history of eyelid blepharoplasty or brow lift within the past 5 years. (6) An inability to substantially reduce GL by physically spreading them apart or lack of capacity to frown. (7) 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). (8) Use of concomitant therapy which, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study treatment, including medications affecting bleeding disorders (e.g. antiplatelet agents and/or anticoagulants given for treatment or prevention of cardiovascular/cerebrovascular diseases). (9) Pregnant women, nursing women, premenopausal women or women of childbearing potential (i.e. not surgically sterile or 1 year postmenopausal) not willing to practice a highly effective form of contraception method at the beginning of the study, for the duration of the study and for a minimum of 12 weeks following last administration of study treatment. Highly effective methods of contraception are defined as methods of birth control which result in a low failure rate (less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices, or vasectomised partner. (10) Male subjects who are not vasectomised and who have female partners of childbearing potential and are not willing to use condoms with spermicide throughout study participation for a minimum of 12 weeks following initial double-blind administration of the treatment. (11) Positive for hepatitis B antigen, or hepatitis C virus antibody, or for human immunodeficiency virus (HIV) or a diagnosis of acquired immunodeficiency syndrome. (12) A history of drug or alcohol abuse. (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 half-life is unknown within 30 days prior to the start of the study (prior to baseline) and during the conduct of the study. (14) Clinically diagnosed significant anxiety disorder, or any other significant psychiatric disorder (e.g. depression) that might interfere with the subject's participation in the study. (15) Use of medications that affect neuromuscular transmission, such as curare-like nondepolarising agents, lincosamides, polymyxins, anticholinesterases and aminoglycoside antibiotics, within the past 30 days prior to Baseline. (16) A history of facial nerve palsy. (17) Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin. (18) Known allergy or hypersensitivity to BTX, or any excipients of IPN59011 or Azzalure, or aller
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the safety and tolerability of increasing doses of a single treatment of IPN59011 compared with placebo in subjects with moderate to severe GL (Glabellar Lines). • To assess the efficacy of IPN59011 compared with placebo in improving the appearance of moderate to severe lines (GL, FHL,LCL) as measured by the Investigator’s Live Assessment (ILA) and subject Self-Assessment (SSA) at maximum contraction at Day 29. • To assess the efficacy of a total dose of IPN59011 compared with placebo in improving the appearance of moderate to severe upper facial lines (GL and FHL and LCL) measured by the ILA and SSA at maximum contraction at Day 29.;Secondary Objective: • To assess the efficacy and safety of increasing and parallel doses of a single treatment of IPN59011 compared with placebo (and/or with Azzalure). • To assess the presence of BoNT-A antibodies and titres (binding and neutralising) and cross reactivity with BoNT-A • To assess the efficacy and safety of parallel doses of a single treatment of IPN59011 compared with placebo. • To assess Face-Q for UFL • To assess the time to onset of treatment response • To determine the duration of treatment response • To assess the presence of IPN59011 antibodies and titres (binding and neutralising). • To assess safety including SAE, TEAEs, AEs or SAEs leading to withdrawal, AESIs, vital signs (absolute values and change from baseline), clinical laboratory evaluations, facial and physical examination, and focused neurological / physical examination. Exploratory: • To assess the PD profile of IPN59011 (CMAP evaluation);Primary end point(s): Efficacy Endpoints: • Safety endpoints • Incidence, severity, and nature, at each dose, of the TEAEs, SAEs, clinically significant AEs, AEs (or SAEs) leading to withdrawals and AESIs. • Vital signs (absolute values and change from Baseline). • Clinical laboratory evaluations. • Presence of botulinum neurotoxin serotype A (BoNT-A) antibodies and IPN59011 antibod | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints : • Response to treatment as measured by the reduction of =2 grades on the ILA at maximum contraction at each post-treatment visit. • Response to treatment as achieved by a score of “none” or “mild” as measured by the ILA at maximum contraction at each post-treatment visit. • Response to treatment as achieved by a score of “none” or “mild” as measured by the ILA at rest at each post-treatment visit. • Response to treatment as measured by the reduction of =2 grades on the SSA at maximum contraction at each post-treatment visit. • Response to treatment as achieved by a score of “none” or “mild” as measured by the SSA at maximum contraction at each post-treatment visit. • Response to treatment as achieved by a score of “very satisfied” or “satisfied” on the SLS at each post-treatment visit • Time to onset of treatment response based on subject diary cards (Day 1 through Day 8). • The duration of treatment response based on the ILA and SSA at maximum contraction. • Face-Q (overall satisfaction with facial appearance) for UFL Exploratory Endpoints: The following pharmacodynamic profile parameters of IPN59011 will be evaluated, based on the CMAP evaluation in corrugator muscle: • Time to onset • Peak effect • Time to peak effect • Duration of action • The percentage of CMAP total amplitude relative to baseline.;Timepoint(s) of evaluation of this end point: Secondary Efficacy Endpoints: • At each post-treatment visit: Visit 3 (Day 2), Visit 4 (Day 3), Visit 5(Day 8), Visit 6 (Day 15), Visit 7 (Day 22; telephone call), Visit 8 (Day29) and then monthly from Visit 9 (Month 2) up to Visit 16 (Month 9) Except for : • Time to onset of treatment response based on subject diary cards : from Day 1 through Day 8 • The duration of treatment response based on the ILA and SSA at maximum contraction.: - each post treatment visits except V4 and V7 for stage1/step1 - each post treatment visits except V5 for stage1/step2, stage 2 an | — |
Countries
Germany
Contacts
Public ContactNeurosciences Therapeutic Area, R&D
Ipsen Innovation
Outcome results
None listed