This study will aim to assess how effective the next generation of BTX-A-HAC (BTX-A-HAC NG) with an injectable liquid formulation is for improving the appearance of lines (wrinkles) between the eyebrows (glabellar area).

• Register: EUCTR
• Last refreshed on: 12 December 2016
• Main ID: EUCTR2013-002321-34-DE
• Date of registration: 19/09/2014
• Prospective Registration: Yes
• Primary sponsor: Ipsen Innovation
• Public title: This study will aim to assess how effective the next generation of BTX-A-HAC (BTX-A-HAC NG) with an injectable liquid formulation is for improving the appearance of lines (wrinkles) between the eyebrows (glabellar area).
• Scientific 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.
• Date of first enrolment: 04/12/2014
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002321-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany

Contacts

• Name: Global Drug Development
• Affiliation: Ipsen Innovation

• Name: Global Drug Development
• Affiliation: Ipsen Innovation

Key inclusion & exclusion criteria

Inclusion criteria:
(1) Provision of written informed consent prior to any study related procedures.
(2) Male or female between 18 and 65 years of age, inclusive.
(3) 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.
(4) 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.
(5) 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.
(6) Have a negative pregnancy test (for females of childbearing potential only). Nonchildbearing potential is defined as post menopausal for at least 1 year, surgical sterilisation at least 3 months before entering the study, or hysterectomy.
(7) Have 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 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
(1) Previous treatment with any serotype of BTX.
(2) Any prior treatment with permanent fillers in the upper face including the glabellar lines area.
(3) Any prior treatment with long lasting dermal fillers in the upper face including the glabella 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.
(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 glabellar lines 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 glabella lines 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 (antiplatelet agents and/or anticoagulants given for treatment or prevention of cardiovasular/cerebrovascular diseases).
(9) 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).
(10) A history of drug or alcohol abuse.
(11) 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.
(12) Known allergy or hypersensitivity to any serotype of BTX or any component of BTX A HAC NG.
(13) 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.
(14) Use of medications that affect neuromuscular transmission, such as curare like nondepolarising agents, lincosamides, polymyxins, anticholinesterases and aminoglycoside antibiotics, within the past 30 days.
(15) A history of facial nerve palsy.
(16) Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin.
(17) 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to severe Glabellar lines
MedDRA version: 17.0 Level: LLT Classification code 10052609 Term: Glabellar frown lines System Organ Class: 100000004858

Therapeutic area: Body processes [G] - Physical Phenomena [G01]

Intervention(s)

Product Name: BTX-A-HAC NG (Dysport NG)
Product Code: BTX-A-HAC NG (Dysport NG)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CLOSTRIDIUM BOTULINUM TOXIN TYPE A
CAS Number: 93384-43-1
Other descriptive name: BOTULINUM TOXIN TYPE A
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Primary end point(s): • The proportion of responders at Day 29 in the ILA of glabellar lines at maximum frown.

Main Objective: The primary study objective is to demonstrate 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 at maximum frown.
The primary objective will be accomplished by demonstrating the superiority of BTX A HAC NG over placebo assessed by the Investigator’s live assessment (ILA) of the appearance of glabellar lines at maximum frown at Day 29.

Secondary Objective: •To compare the efficacy of a single treatment of BTX A HAC NG to placebo at all timepoints (except Day 29), using the ILA of the appearance of glabellar lines at maximum frown.
•To compare the efficacy of a single treatment of BTX A HAC NG to placebo at all timepoints, using the ILA of the appearance of glabellar lines at rest.
•To compare the efficacy of a single treatment of BTX A HAC NG to placebo at all timepoints, using the subject’s self assessment (SSA) of the appearance of glabellar lines at maximum frown.
•To compare the subject’s level of satisfaction with the appearance of their glabellar lines following treatment with BTX A HAC NG or placebo.
•To determine the time to onset of treatment response.
•To determine the duration of treatment response.
•To compare the safety of a single treatment of BTX A HAC NG to placebo in the treatment of glabellar lines.

Timepoint(s) of evaluation of this end point: Day 29

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Each post-treatment visit to the study centre (except Day 29)
2. Responsders on Day 29 who remain responders on Days 113, 148 and 183
3. At each post-treatment visit.
4. At each post-treatment visit to the study centre as measured by the subject’s self-assessment.

Secondary end point(s): • The proportion of responders at each post treatment visit to the study centre (except Day 29) as measured by the ILA at maximum frown.
• The proportion of responders on Day 29 who remain responders on Days 113, 148 and 183 as measured by the ILA at maximum frown.
• The proportion of responders at each post treatment visit to the study centre as measured by the ILA at rest.
• 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.
• The proportion of responders at each post treatment visit to the study centre as measured by the SSA at maximum frown.
• 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.
• The time to onset of treatment response based on the subject’s diary card.
• Duration of treatment response based on the ILA and SSA at maximum frown.

Secondary ID(s)

Y-52-52120-189

Source(s) of Monetary Support

Ipsen Innovation