Dysport in the Treatment of Glabellar Lines in Chinese Subjects

Glabellar Lines Clinical Trial

Official title:

A Phase III, Randomised, Double Blind and Open Label Phase, Multicentre, Active and Placebo Controlled Study to Investigate the Efficacy and Safety of Dysport Including a Comparison to Botox in the Treatment of Moderate to Severe Glabellar Lines, and to Assess the Long Term Efficacy and Safety of Dysport Following Repeated Treatments in This Indication

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02450526
• Other study ID #: Y-52-52120-158
• Status: Completed
• Phase: Phase 3
• Start date: April 2015
• Est. completion date: September 6, 2017

Study information

• Verified date: July 2019
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to demonstrate the efficacy of Dysport for the improvement in appearance of moderate to severe glabellar lines and to assess the short term and long term safety of Dysport, used for the improvement in appearance of moderate to severe glabellar lines in Chinese subjects.

Description:

The first treatment cycle will be double blind and subjects will be randomised to receive Dysport, Botox or placebo. After the first treatment cycle, all subjects will receive a maximum of four treatment cycles with Dysport, occurring at intervals of no less than 84 Days (12 weeks) between each treatment cycle, depending upon individual duration of response to Dysport treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 520
• Est. completion date: September 6, 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Provision of written informed consent

• Male or female Chinese subjects who are between 18 to 65 years of age inclusive.

• Have moderate or severe wrinkles of vertical glabellar lines (Grade 2 or 3) at maximum frown at baseline (Day 1), as assessed by the subject using SSA.

• Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at baseline (Day 1), as assessed by the Investigator using ILA.

• Be Botulinum Toxin (BTX) naïve or have received their most recent BTX-A treatment more than 1 year prior to screening.

• Have a negative pregnancy test

• Have an understanding of the study

Exclusion Criteria:

• Any prior surgery affecting corrugator supercilii, prior blepharoplasty or brow lift, dermal resurfacing, or any prior cosmetic procedures or scars within 36 months.

• Any prior treatment with permanent fillers in the upper face.

• Any prior treatment with nonpermanent dermal fillers in the upper face within the past 3 years and/or skin abrasions/resurfacing, photorejuvenation or skin/vascular laser intervention within the past 12 months.

• Any planned facial cosmetic surgery or procedures during the study period.

• Lack of capacity to frown.

• Facial conditions that could affect safety or efficacy results.

• History of facial nerve palsy.

• Marked asymmetry; ptosis; excessive dermatochalasis; deep dermal scarring; thick sebaceous skin; photodamage etc.

• Presence of any condition that could affect the safety, conduct or outcome of the study.

• Any subjects who have any psychiatric illness or are taking antidepressant, anxiolytic or antipsychotic medication.

• Pregnant and/or lactating female subjects.

• Female subjects of childbearing potential not willing to use contraceptive measures throughout the course of the study.

• History of drug or alcohol abuse.

• Treatment with an experimental drug or device within 30 days prior to screening for this study and during the conduct of this study.

• Requirement for BTX injection to site(s) for disorders other than glabellar lines.

• Known allergy or hypersensitivity to BTX.

• Any medical condition or laboratory finding from central laboratory results.

• The subject is unable and/or unwilling to comply fully with the protocol and the study.

• Mental incapacity, unwillingness or language barriers.

Related Conditions & MeSH terms

• Glabellar Lines

Intervention

Biological:
• Botulinum toxin type A

• Botulinum toxin type A

Drug:
• Placebo
50 Units
• Placebo
20 Units

Locations

Country	Name	City	State
China	Air Force General Hospital, PLA	Beijing
China	Chinese PLA General Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Peking University First Hospital	Beijing
China	The Third Xiangya Hospital of Central South University	Changsha
China	West China Hospital, Sichuan University	Chengdu
China	The Third Affiliated Hospital of Sun Yat-sen University	Guanzhou
China	Dermatology Hospital of the Chinese Academy of Medical Sciences	Nanjing
China	Tianjin Medical University General Hospital	Tianjing
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The Percentage of Responders Measured by the ILA at Maximum Frown at Cycle 1 Study Visits (DB Period).	At baseline (Cycle 1, Day 1) and at all subsequent study visits, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point photographic scale of glabellar line severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at any given visit, and a severity grade of 2 or 3 at baseline.; Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29).	Up to Cycle 1, Day 85.
Other	The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1 Study Visits (DB Period).	At baseline (Cycle 1, Day 1) and all subsequent study visits, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of 0 or 1 at maximum frown at any given visit, and a severity grade of 2 or 3 at maximum frown at baseline.; Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29).	Up to Cycle 1, Day 85.
Other	The Percentage of Responders Measured by the ILA at Rest at Cycle 1 Study Visits (DB Period).	At baseline (Cycle 1, Day 1) and at all subsequent study visits, the Investigator assessed the appearance of the glabellar lines at rest using a validated 4-point photographic scale of glabellar line severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at rest at any given visit, and a severity grade of 2 or 3 at rest at baseline.; Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29).	Up to Cycle 1, Day 85.
Other	The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 85 (DB Period).	Photographs of the glabellar region of subjects were taken at baseline and at maximum frown at Cycle 1, Day 85. Photographs were assessed by an Independent Experts Committee using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). The median of 3 readings by 3 independent reviewers was used in the analysis. A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 85, and a severity grade of 2 or 3 at baseline.; Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 85 .	At Cycle 1, Day 85.
Other	Mean SGA Score at Cycle 1 Study Visits (DB Period).	On all study visits, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50% worsening; -3 =75% worsening; -4 =100% worsening.; The mean SGA score for study visits on Day 8 to Day 85 in the DB period is presented (except Cycle 1, Day 29).	Up to Cycle 1, Day 85.
Other	The Percentage of Responders With Respect to the SGA Score at Cycle 1 Study Visits (DB Period).	On all study visits, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement).; Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for all visits up to Day 85 in the DB period (except Cycle 1, Day 29).	Up to Cycle 1, Day 85.
Other	Least Squares (LS) Mean Change From Baseline in Subject's Self-perception of Age at Cycle 1 Study Visits (DB Period).	At baseline (Cycle 1, Day 1) and all subsequent study visits in Cycle 1, subjects were asked to evaluate their age over the past 7 days at the time of assessment, using the following categories: I look like my current age; I look _ years younger; I look _ years older.; The LS mean change from baseline in subject's self-perception of age at all study visits in the DB Period was calculated. A negative LS mean change from baseline in the subject's self-perception of age indicates that the subject's self-perception was to look younger compared with baseline.	Up to Cycle 1, Day 85.
Other	The Time to Onset of Treatment Response Based on the Subject's Diary Card (DB Period).	Subjects were given the diary card at baseline (Cycle 1, Day 1 ) and asked to record their assessment of study treatment response for the first 7 days post-treatment (Days 2 to 8). They were asked to respond '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)?' Subjects with no treatment response were censored at the date of last assessment of treatment response recorded in the diary card.; The 50th percentile of Kaplan-Meier estimates was used to estimate the median time to onset of treatment response for each treatment group.	At Cycle 1, Day 8.
Other	The Percentage of Responders Measured by the ILA at Maximum Frown at All Other Study Visits (OL Period).	At baseline (Cycle 1, Day 1) and all subsequent study visits (per treatment cycle) in the OL period, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at each study visit, and a severity grade of 2 or 3 at baseline.; The proportion (percentage) of responders measured by ILA at all study visits in each treatment cycle, is presented.	Up to Cycle 5, Day 85.
Other	The Percentage of Responders Measured by the SSA at Maximum Frown at All Other Study Visits (OL Period).	At baseline (Cycle 1, Day 1) and all subsequent study visits per treatment cycle in the OL period, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of no wrinkles (0) or mild wrinkles (1) at maximum frown at a given visit and a severity grade of moderate wrinkles (2) or severe wrinkles (3) at maximum frown at baseline.; The proportion (percentage) of responders measured by SSA at all study visits in Cycle 2 to 5 is presented.	Up to Cycle 5, Day 85.
Other	The Percentage of Responders Measured by the ILA at Rest at All Study Visits (OL Period).	At baseline (Cycle 1, Day 1) and all subsequent study visits per treatment cycle in the OL period, the Investigator assessed the appearance of the glabellar lines at rest using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at a given visit, and a severity grade of 2 or 3 at baseline. Subjects with a baseline score of 0 or 1 were excluded from the analysis of responders. The proportion (percentage) of responders measured by ILA at all study visits per treatment cycle in in the OL period is presented.	Up to Cycle 5, Day 85.
Other	Mean SGA Score at All Other Study Visits (OL Period).	On each study visit per treatment cycle in the OL period, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening.; The mean SGA score for study visits on Day 8 to Day 85 in the OL period is presented.	Up to Cycle 5, Day 85.
Other	The Proportion of Responders With Respect to the SGA Score at All Other Study Visits (OL Period).	On each study visit per treatment cycle in the OL period, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening.; A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement). The proportion (percentage) of responders at each study visit on Day 8 to Day 85 in the OL period is presented.	Up to Cycle 5, Day 85.
Other	Mean Change From Baseline in Subject's Self-Perception of Age at All Study Visits (OL Period)	At cycle baseline (Day 1 of each treatment cycle) and Day 29 of each cycle in the OL period, subjects were asked to evaluate their age over the past 7 days at the time of assessment, using the following categories: I look like my current age; I look _ years younger; I look _ years older.; The mean change from cycle baseline in subject's self-perception of age at Day 29 of each cycle of the OL Period was calculated. A negative mean change from baseline in the subject's self-perception of age indicates that the subject's self-perception was to look younger compared with baseline.	Up to Cycle 5, Day 29.
Primary	Superiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period).	At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline.; Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.	At Cycle 1, Day 29.
Primary	Superiority Analysis of The Percentage of Responders Measured by the SSA at Maximum Frown at Cycle 1, Day 29 (DB Period).	At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, subjects assessed the appearance of their glabellar lines at maximum frown using a 4-point categorical scale. The 4-point scale represents the severity of glabellar lines as Grade 0 (no wrinkles), Grade 1 (mild wrinkles), Grade 2 (moderate wrinkles) and Grade 3 (severe wrinkles). For the SSA, a responder was defined as having a severity grade of 0 or 1 at maximum frown at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline.; Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.	At Cycle 1, Day 29.
Primary	Non-Inferiority Analysis of The Percentage of Responders Measured by the Investigator's Live Assessment (ILA) at Maximum Frown at Cycle 1, Day 29 (DB Period).	At baseline (Cycle 1, Day 1) and at Cycle 1, Day 29, the Investigator assessed the appearance of the glabellar lines at maximum frown using a validated 4-point Photographic Scale of Glabellar Line Severity. This 4-point scale rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at maximum frown at baseline.; Non Inferiority analysis of Dysport® versus Botox was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.	At Cycle 1, Day 29.
Secondary	The Percentage of Responders With Respect to Independent Reviewer's Assessment of Photographs of the Subject's Glabellar Lines at Maximum Frown at Cycle 1, Day 29 (DB Period).	Photographs of the glabellar region of subjects were taken at maximum frown at baseline (Cycle 1, Day 1) and at Cycle 1, Day 29. Photographs were assessed by an Independent Experts Committee using a validated 4-point Photographic Scale of Glabellar Line Severity which rated the severity of glabellar lines as Grade 0 (none), Grade 1 (mild), Grade 2 (moderate) and Grade 3 (severe). The median of three readings by three independent reviewers was used in the analysis. A responder was defined as having a severity grade of 0 or 1 at Cycle 1, Day 29, and a severity grade of 2 or 3 at baseline.; Superiority analysis of active treatment to placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.	At Cycle 1, Day 29.
Secondary	Mean Subject's Global Assessment (SGA) Score at Cycle 1, Day 29 (DB Period).	On Cycle 1, Day 29, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50%worsening; -3 =75% worsening; -4 =100% worsening.; The mean SGA score at Cycle 1, Day 29 is presented.	At Cycle 1, Day 29.
Secondary	The Percentage of Responders With Respect to the SGA Score at Cycle 1, Day 29 (DB Period).	On Cycle 1, Day 29, subjects were asked to assess the change, since the last treatment administration, in the appearance of their glabellar lines using the following 9-point Global Assessment Scale: +4 =100% improvement; +3 =75% improvement; +2 =50% improvement; +1 =25% improvement; 0 =no change; -1 =25% worsening; -2 =50% worsening; -3 =75% worsening; -4 =100% worsening. A responder, based on the SGA scale, was defined as having a grade of at least +2 (50% improvement).; Superiority analysis of active treatment versus placebo was carried out using a multivariate logistic regression model and adjusted for the stratification factors of gender and baseline severity score of glabellar lines at maximum frown measured by the ILA. The adjusted percentage of responders is presented for Cycle 1, Day 29.	At Cycle 1, Day 29.