Efficacy and Safety of Clostridium Botulinum Toxin Type A to Improve Appearance of Moderate to Severe Glabellar Lines

NCT02353871 | Completed Phase 3 Results

• 2 other identifiers: Y-52-52120-1892013-002321-34
• Study Type: interventional
• Target: 185
• Locations: 2 countries
• Sites: 9

Brief 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 to severe glabellar lines (the lines between the eyebrows).

Conditions

Moderate to Severe Glabellar Lines

Keywords

Moderate to Severe

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  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.

  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.

  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.

  Day 8, 15, 29, 57, 85, 113, 148 and 183

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Botulinum toxin type A BIOLOGICAL

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).

Also known as: BTX-A-HAC NG

BTX-A-HAC NG

Placebo DRUG

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).

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (9)

Nouvelle Clinique Bel Air

Bordeaux, 33200, France

Location

Cabinet Medical

Cannes, 06400, France

Location

Mediti

Juan-les-Pins, 06160, France

Location

Clinique IENA

Paris, 75116, France

Location

Rzany & Hund Privatpraxis für Dermatologie

Berlin, 10707, Germany

Location

Medical Skin Center

Düsseldorf, 40212, Germany

Location

University of Hamburg

Hamburg, 20146, Germany

Location

Rote Kreuz Krankenhaus

Kassel, 34121, Germany

Location

Hautzentrum am Starnberger See

Starnberg, 82319, Germany

Location

Related Publications (1)

• 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.

  PMID: 36206385 DERIVED

MeSH Terms

Interventions

Botulinum Toxins, Type A

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Limitations and Caveats

Median could not be calculated because insufficient number of participants with events in the placebo group (3 events for ILA and 8 for SSA).

Results Point of Contact

• Title: Medical Director, Neurology
• Organization: Ipsen

clinical.trials@ipsen.com

clinical.trials@ipsen.com

Study Officials

• Ipsen Study Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 3, 2015
• Study Start: January 1, 2015
• Primary Completion: April 1, 2015
• Study Completion: August 1, 2015
• Last Updated: September 28, 2022
• Results First Posted: October 2, 2017

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Locations

FR (4); DE (5)