Clinical trial NCT02493946: Efficacy and Safety of Botulinum Toxin Type A Haemagglutinin Complex Next Generation (BTX-A-HAC NG) in Glabellar Lines
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glabellar Lines
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2015-07-10
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.
* Known allergy or hypersensitivity to any component of BTX-A-HAC NG.
* 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.
* 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.
* A history of facial nerve palsy.
* Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin.
* The presence of any other condition (e.g. neuromuscular disorder or other disorder that could interfere with neuromuscular function), laboratory finding or circumstance that, in the judgement of the investigator, might increase the risk to the subject or decrease the chance of obtaining satisfactory data to achieve the objectives of the study.

Primary outcomes:
measure: 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
timeFrame: Day 29 (Cycle 1)
Secondary outcomes:
measure: The Percentage of Responders at Each Post-treatment Visit (Except Day 29 Cycle 1) as Measured by the ILA at Maximum Frown: DB Period
timeFrame: Days 8, 57 and 85 (Cycle 1).
measure: 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
timeFrame: Days 29, 57 and 85 (Cycle 1).
measure: The Percentage of Responders at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Rest: DB Period
timeFrame: Days 8, 29, 57 and 85 (Cycle 1).
measure: 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
timeFrame: Days 8, 29, 57 and 85 (Cycle 1).
measure: 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
timeFrame: Days 8, 29, 57 and 85 (Cycle 1).
measure: The Median Time to Onset of Treatment Response Based on the Subject's Diary Card: DB Period
timeFrame: Days 1 to 7 (Cycle 1).
measure: Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: DB Period
timeFrame: Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).
measure: Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: DB Period
timeFrame: Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).
measure: Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal Visual Analogue Scale (VAS): DB Period
timeFrame: Baseline (Day 1) and Days 8, 29, 57 and 85 (Cycle 1).
measure: The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Maximum Frown: LT Analyses
timeFrame: Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).
measure: The Percentage of Responders at Each Post-treatment Visit as Measured by the ILA at Rest: LT Analyses
timeFrame: Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).
measure: The Percentage of Responders at Each Post-treatment Visit as Measured by the SSA at Maximum Frown: LT Analyses
timeFrame: Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).
measure: 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
timeFrame: Days 8, 29, 57 and 85 of Cycles 1 - 5 (up to 15 months).
measure: Median Time to Retreatment in LT Analysis
timeFrame: Cycles 1 - 4 (up to 12 months).
measure: Change From Baseline at All Post-treatment Visits in the FACE-Q Satisfaction With Facial Appearance Overall Scale: LT Analyses
timeFrame: Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.
measure: Change From Baseline at All Post-treatment Visits in the FACE-Q Psychological Well-being Scale: LT Analyses
timeFrame: Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.
measure: Change From Baseline at All Post-treatment Visits in the FACE-Q Aging Appearance Appraisal VAS: LT Analyses
timeFrame: Days 8, 29, 57 and 85 of Cycles 1 to 3; Days 8, 29 and 85 of Cycles 4 and 5.
Other outcomes:
Locations:
city: Arras
country: France
facility: Centre Médical Saint-Jean
city: Besançon cedex
country: France
facility: CHRU Hôpital
city: Cannes
country: France
facility: Cabinet Médical
city: Juan les Pins
country: France
facility: MEDITI/ Clinique Science et Beauté, Villa Sylvana
city: Lyon
country: France
facility: Palais de Flore
city: Paris
country: France
facility: Clinique Iéna
city: Berlin
country: Germany
facility: Dermatologisches Studienzentrum
city: Berlin
country: Germany
facility: Privatpraxis für Dermatologie und ästhetische Medizin
city: Darmstadt
country: Germany
facility: Klinik
city: Darmstadt
country: Germany
facility: Rosenpark Research
city: Düsseldorf
country: Germany
facility: Medical Skin Center
city: Frankfurt
country: Germany
facility: Klinik für Dermatologie
city: Kassel
country: Germany
facility: Abteilung Biochemie und Molekularbiologie Fachrichtung Kosmetikwissenschaft
city: Kassel
country: Germany
facility: Rote Kreuz Krankenhaus
city: Ludwigshafen
country: Germany
facility: Klinik
city: Mahlow
country: Germany
facility: Hautarztpraxis Mahlow
city: Mainz
country: Germany
facility: Universitäts-Hautklinik der Gutenberg Universität Mainz
city: München
country: Germany
facility: Privatpraxis für Dermatologie und Ästhetik
city: Münster
country: Germany
facility: Praxisklinik
city: Osnabrück
country: Germany
facility: Klinische Forschung Osnabrück
city: Starnberg
country: Germany
facility: Hautzentrum am Starnberger See
city: Wuppertal
country: Germany
facility: Praxis für Dermatologie und Venerologie
city: London
country: United Kingdom
facility: London Bridge Plastic Surgery
city: London
country: United Kingdom
facility: PHI clinic
Study officials:
affiliation: Ipsen
name: Ipsen Study Director
role: STUDY_DIRECTOR
References:
citation: Hilton S, Kestemont P, Sattler G, Volteau M, Thompson C, Andriopoulos B, Prygova I, Berg AK, Ascher B. Liquid AbobotulinumtoxinA: Pooled Data From Two Double-Blind, Randomized, Placebo-Controlled Phase III Studies of Glabellar Line Treatment. Dermatol Surg. 2022 Nov 1;48(11):1198-1202. doi: 10.1097/DSS.0000000000003594. Epub 2022 Oct 7.