Moderate to Severe Glabellar LinesPhase 3BTX-A-HAC NGNCT02353871
Efficacy and Safety of Clostridium Botulinum Toxin Type A to Improve Appearance of Moderate to Severe Glabellar Lines
A Phase 3 study testing Botulinum toxin type A in people with Moderate to Severe Glabellar Lines, run by Ipsen at 9 sites in 2 countries.
Trial summary
The purpose of this study was to demonstrate the safety and the efficacy of a single treatment of an injectable liquid form of Clostridium botulinum toxin type A haemagglutinin complex (BTX-A-HAC; hereafter referred to as BTX-A-HAC Next Generation (BTX-A-HAC NG)), used for the improvement in the appearance of moderate… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Moderate to Severe Glabellar Lines
- What is being tested?
- Botulinum toxin type A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 185 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Jan 2015to Aug 2015
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent prior to any study related procedures.
- Male or female between 18 and 65 years of age, inclusive.
- Had 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.
- Had 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.
- Were 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.
- Had a negative pregnancy test (for females of childbearing potential only). Nonchildbearing potential was defined as post menopausal for at least 1 year, surgical sterilisation at least 3 months before entering the study, or hysterectomy.
- Had both the time and the ability to complete the study and comply with study instructions.
Who cannot join
- Previous treatment with any serotype of botulinum toxin (BTX).
- Any prior treatment with permanent fillers in the upper face including the glabellar lines area.
- Any prior treatment with long lasting 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 photorejuvenation 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 lift within the past 5 years.
- An inability to substantially reduce glabellar lines by physically spreading them apart or lack of capacity to frown.
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- 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 have interfered with the evaluation of the safety or efficacy of the study treatment, including medications affecting bleeding disorders (antiplatelet agents and/or anticoagulants given for treatment or prevention of cardiovascular/cerebrovascular diseases).
- Pregnant women, nursing mothers, or women who were planning a pregnancy during the study, or believed they may be pregnant at the start of the study. Throughout the course of the study, women of childbearing potential had to use a reliable form of contraception (e.g. oral contraceptives for more than 12 consecutive weeks, or spermicide and condoms).
- A history of drug or alcohol abuse.
- 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 serotype of BTX or 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 nondepolarising 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.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Germany5 sites
Rzany & Hund Privatpraxis für Dermatologie
Berlin, 10707
Medical Skin Center
Düsseldorf, 40212
University of Hamburg
Hamburg, 20146
Rote Kreuz Krankenhaus
Kassel, 34121
Hautzentrum am Starnberger See
Starnberg, 82319
France4 sites
Nouvelle Clinique Bel Air
Bordeaux, 33200
Cabinet Medical
Cannes, 06400
Mediti
Juan-les-Pins, 06160
Clinique IENA
Paris, 75116
About this study
Official title: A Phase III, Double Blind, Randomised, Placebo Controlled Study To Assess The Efficacy And Safety Of A Single Treatment Of Clostridium Botulinum Toxin Type A To Improve The Appearance Of Moderate To Severe Glabellar Lines
The purpose of this study was to demonstrate the safety and the efficacy of a single treatment of an injectable liquid form of Clostridium botulinum toxin type A haemagglutinin complex (BTX-A-HAC; hereafter referred to as BTX-A-HAC Next Generation (BTX-A-HAC NG)), used for the improvement in the appearance of moderate to severe glabellar lines (the lines between the eyebrows).
Read the detailed description
At the Baseline Visit (Day 1), subjects were randomised in a ratio of 2:1 to receive either BTX-A-HAC NG solution (50 U) or placebo. Randomisation was stratified according to gender and severity of glabellar lines at maximum frown (moderate to severe) at Baseline. A single dose of BTX-A-HAC NG solution 50 U or placebo was injected on Day 1. Subjects were then monitored at the study centre for 30 minutes. On Day 4, subjects were contacted by telephone for adverse event monitoring and to record concomitant medications and treatments.
Subjects attended follow-up visits at the study centre on Days 8, 15, 29, 57, 85, 113, 148 and 183. The Day 183 follow-up visit was the end of study visit; all subjects who had completed the Day 183 Visit were considered to have completed the study.
- Conditions
- Moderate to Severe Glabellar Lines
- Being tested
- Botulinum toxin type A, Placebo
- Keywords
- Moderate to Severe
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum toxin type ABiological
Also called BTX-A-HAC NG
A solution containing 50 U in 0.25 mL (200 U/mL). Each vial contained 0.625 mL of deliverable volume of solution. A volume of 0.25 mL, containing 50 U of BTX-A-HAC NG (i.e. 10 U/0.05 mL) was withdrawn from the vial into a syringe for administration. The total treatment volume (0.25 mL) was divided into five injections (0.05 mL per injection), each of which was to be administered into predefined sites across the glabellar region (two injections into each corrugator muscle and one injection into the procerus muscle).
PlaceboDrug
A solution containing only the excipients of BTX-A-HAC NG (identical in appearance to the active product). Each vial contained 0.625 mL of deliverable volume of solution. A volume of 0.25 mL was withdrawn from the vial into a syringe for administration. The total treatment volume (0.25 mL) was divided into five injections (0.05 mL per injection), each of which was to be administered into predefined sites across the glabellar region (two injections into each corrugator muscle and one injection into the procerus muscle).
| Study group | Role | What they receive |
|---|---|---|
| BTX-A-HAC NG | Experimental | Clostridium Botulinum Toxin Type A (BTX-A-HAC NG) 50 Unit (U) solution, single dose (intramuscular injection). The total treatment volume (0.25 mL) was divided into five injections (0.05 mL per injection) injected in five predefined sites across the glabellar region. A total of 50 U was injected. Receives: Biological: Botulinum toxin type A |
| Placebo | Placebo comparator | Single dose (intramuscular injection). The total placebo volume (0.25 mL) was divided into five injections (0.05 mL per injection) injected in five predefined sites across the glabellar region. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Proportion of Responders at Day 29 in the ILA of Glabellar Lines at Maximum Frown.
ILA
4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3.
A responder at maximum frown was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at maximum frown on Day 29 and a severity grade of moderate (Grade 2) or severe (Grade 3) at Baseline (Day 1).
The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Measured: Day 29
Secondary outcomes (7)
The Proportion of Responders at Each Post-treatment Visit to the Study Centre (Except Day 29) as Measured by the ILA at Maximum Frown.
ILA
4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3.
A responder at maximum frown was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at maximum frown at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at Baseline (Day 1).
The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Measured: Day 8, 15, 57, 85, 113, 148 and 183
The Proportion of Responders on Day 29 Who Remained Responders on Days 57, 85, 113, 148 and 183 as Measured by the ILA at Maximum Frown.
ILA
4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3.
A responder at maximum frown was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at maximum frown at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at Baseline (Day 1). Subjects who were not responders at Day 29 were excluded from the analysis.
The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Measured: Day 57, 85, 113, 148 and 183
The Proportion of Responders at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Rest.
ILA
4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3.
A responder at rest was defined as having a severity grade of none (Grade 0) or mild (Grade 1) at rest at a given visit and a severity grade of moderate (Grade 2) or severe (Grade 3) at Baseline (Day 1).
The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Measured: Day 8, 15, 29, 57, 85, 113, 148 and 183
The Proportion of Subjects With a Reduction of Two or More Grades in the Severity of Glabellar Lines at Each Post-treatment Visit to the Study Centre as Measured by the ILA at Maximum Frown.
ILA
4-point photographic scale: None - Grade 0; mild - Grade 1; moderate - Grade 2; severe - Grade 3.
Adjusted proportion of subjects with a reduction of two or more grades in the severity of glabellar lines at each post-treatment visit compared with Baseline.
The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Measured: Day 8, 15, 29, 57, 85, 113, 148 and 183
The Proportion of Responders at Each Post-treatment Visit to the Study Centre as Measured by the Subject's Self-assessment (SSA) at Maximum Frown.
SSA
4-point photographic scale: No wrinkles - 0; Mild wrinkles - 1; Moderate wrinkles - 2; Severe wrinkles - 3.
A responder at maximum frown was defined as having a severity grade of no wrinkles (Grade 0) or mild wrinkles (Grade 1) at maximum frown at a given visit and a severity grade of moderate wrinkles (Grade 2) or severe wrinkles (Grade 3) at Baseline (Day 1).
The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Measured: Day 8, 15, 29, 57, 85, 113, 148 and 183
The Proportion 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.
Adjusted proportion of responders at each post-treatment visit (measured by the subject's level of satisfaction with the appearance of their glabellar lines).
4-point categorical scale: Grade 0 - very satisfied; Grade 1 - satisfied; Grade 2 - dissatisfied; Grade 3 - very dissatisfied.
A responder was defined as having a satisfaction rating of very satisfied (Grade 0) or satisfied (Grade 1) at a given visit and a satisfaction rating of dissatisfied (Grade 2) or very dissatisfied (Grade 3) at Baseline (Day 1).
The adjusted proportion of responders in each treatment group was provided using a multivariate logistic regression model.
Measured: Day 8, 15, 29, 57, 85, 113, 148 and 183
The Time to Onset of Treatment Response Based on the Subject's Diary Card.
Median time to onset of treatment response: subjects asked to record their assessment of study treatment response in a diary card on Days 1 to 7. They responded 'yes' or 'no' to the following question: 'since being injected have you noticed an improvement in the appearance of your glabellar lines (lines between your eyebrows)?'
Measured: Day 1 to 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionApr 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Moderate to Severe Glabellar LinesStudies of the same condition, open and under way.
- More trials run by IpsenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ipsen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Study Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02353871
- Sponsor's protocol ID
- Y-52-52120-189
- Other IDs
- 2013-002321-34
- Acronym
- BTX-A-HAC NG
- Status last verified
- Sep 2022
- First submitted
- 29 Jan 2015
- Last updated
- 28 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
Publications
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.
PubMed 36206385