Phase III, Randomised, Double Blind, Placebo Controlled and Open Label Phase Multicentre Study to Investigate the Efficacy and Safety of BTX-A-HAC NG in the Treatment of Moderate to Severe Glabellar Lines, and Assess the Long Term Efficacy and Safety of BTX-A-HAC NG Following Repeated Treatments in This Indication
Overview
- Phase
- Phase 3
- Intervention
- Botulinum toxin type A
- Conditions
- Glabellar Lines
- Sponsor
- Ipsen
- Enrollment
- 600
- Locations
- 23
- Primary Endpoint
- The Percentage of Responders at Day 29 Cycle 1 as Measured by Investigator's Live Assessment (ILA) of Glabellar Lines at Maximum Frown: DB Period
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of the protocol is to demonstrate the safety and the efficacy of a single injection of a new formulation of Clostridium Botulinum toxin type A haemagglutinin complex (BTX A HAC NG) to improve the appearance of moderate to severe glabellar lines (the lines between the eyebrows) and to assess the long term efficacy and safety of BTX-A-HAC NG after repeated injections.
Detailed Description
This is a multicentre study conducted in two periods. Subjects will first be enrolled to enter the double blind (DB) period Cycle 1. Subjects who are eligible for retreatment will then be offered to enter open label (OL) Cycles 2 to 5 as DB roll-over subjects. Once recruitment of the DB period is complete, the study will enrol additional BTX-naïve subjects (hereafter referred to as OL de novo subjects) into the OL period Cycle 1. All OL de novo subjects who are eligible for retreatment will also be offered to enter OL Cycles 2 to 5. A total of 580 subjects (180 subjects randomised in the DB period and an additional 400 de novo subjects in the OL period) are planned to complete the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of written informed consent prior to any study related procedures.
- •Male or female subjects between 18 and 65 years of age.
- •Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at Baseline (Day 1), as assessed by the ILA using a validated 4- point photographic scale.
- •Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at Baseline (Day 1), as assessed by the SSA using a validated 4-point categorical scale.
- •Are dissatisfied or very dissatisfied (Grade 2 or 3) with their glabellar lines at Baseline (Day 1), as assessed by the subject's level of satisfaction.
- •Have a negative pregnancy test (for females of childbearing potential only). No childbearing potential is defined as post-menopausal for at least 1 year, surgical sterilisation at least 3 months before entering the study, or hysterectomy.
- •Have both the time and the ability to complete the study and comply with study instructions.
Exclusion Criteria
- •Previous treatment with any serotype of BTX.
- •Any prior treatment with permanent fillers in the upper face including the glabellar lines area.
- •Any prior treatment with any dermal fillers in the upper face including the glabellar lines 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 past 12 months.
- •Any planned facial cosmetic surgery during the study.
- •A history of eyelid blepharoplasty or brow lifts within the past 5 years.
- •An inability to substantially reduce glabellar lines by physically spreading them apart or lack of capacity to frown.
- •An active infection or other skin problems in the upper face including the glabellar lines area (e.g. acute acne lesions or ulcers).
- •Use of concomitant therapy, which in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the investigational medicinal product (IMP), including medications affecting bleeding disorders (antiplatelet agents and/or anticoagulants given for treatment or prevention of cardio/cerebro vascular diseases).
- •Pregnant women, nursing mothers, or women who are planning a pregnancy during the study, or believe they may be pregnant at the start of the study. Throughout the course of the study, women of childbearing potential must use a reliable form of contraception (e.g. oral contraceptives for more than 12 consecutive weeks, or spermicide and condoms).
- •Treatment with an experimental drug or use of any experimental device within 30 days prior to the start of the study and during the conduct of the study.
Arms & Interventions
BTX-A-HAC NG
Clostridium Botulinum Toxin Type A (BTX A HAC NG), total treatment volume 0.25mL will be divided into 5 injections (0.05mL per injections) injected in 5 pre-defined sites across the glabellar region. A total of 50 Units of BTX-A-HAC NG will be injected/ cycle.
Intervention: Botulinum toxin type A
Placebo
The total placebo volume 0.25mL will be divided into 5 injections (0.05mL per injections) injected in 5 pre-defined sites across the glabellar region. Administered in Cycle 1 of the double blind phase only.
Intervention: Placebo
Outcomes
Primary Outcomes
The Percentage of Responders at Day 29 Cycle 1 as Measured by Investigator's Live Assessment (ILA) of Glabellar Lines at Maximum Frown: DB Period
Time Frame: Day 29 (Cycle 1)
The appearance of glabellar lines at maximum frown was assessed in the DB period at the Day 29 follow-up visit using the ILA, a validated 4-point photographic scale of glabellar line severity. A responder was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at baseline (Day 1 Cycle 1). The adjusted percentage of responders (determined by multivariate logistic regression analysis) at Day 29 of Cycle 1 is presented.
Secondary Outcomes
- The Percentage of Responders on Day 29 Cycle 1 Who Remained Responders on Days 57 and 85 as Measured by the ILA at Maximum Frown: DB Period(Days 29, 57 and 85 (Cycle 1).)
- The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Rest: DB Period(Days 8, 29, 57 and 85 (Cycle 1).)
- The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the Subject's Level of Satisfaction With the Appearance of Their Glabellar Lines: DB Period(Days 8, 29, 57 and 85 (Cycle 1).)
- The Median Time to Onset of Treatment Response Based on the Subject's Diary Card: DB Period(Days 1 to 7 (Cycle 1).)
- Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: DB Period(Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).)
- The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Maximum Frown: LT Analyses(Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).)
- The Percentage of Responders at Each Post-treatment Visit (Except Day 29 Cycle 1) as Measured by the ILA at Maximum Frown: DB Period(Days 8, 57 and 85 (Cycle 1).)
- Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal VAS: LT Analyses(Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.)
- The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the Subject's Self-Assessment (SSA) at Maximum Frown: DB Period(Days 8, 29, 57 and 85 (Cycle 1).)
- Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: DB Period(Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).)
- Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal Visual Analogue Scale (VAS): DB Period(Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).)
- The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Rest: LT Analyses(Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).)
- The Percentage of Responders at Each Post-treatment Visit as Measured by the SSA at Maximum Frown: LT Analyses(Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).)
- The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the Subject's Level of Satisfaction With the Appearance of Their Glabellar Lines: LT Analyses(Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).)
- Median Time to Retreatment in LT Analysis(Cycles 1 - 4 (up to 12 months).)
- Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: LT Analyses(Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.)
- Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: LT Analyses(Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.)