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出境医 / 临床实验 / Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study III (BLESSIII) (BLESSIII)

Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study III (BLESSIII) (BLESSIII)

Study Description
Brief Summary:
The aim of this study is to assess the efficacy and safety of BoNT/A-DP in the treatment of glabellar lines in comparison with placebo, including efficacy after repeat treatments and long term safety.

Condition or disease Intervention/treatment Phase
Glabellar Frown Lines Drug: Botulinum Toxin A Drug: Placebo Phase 3

Detailed Description:

The study is a parallel-group, randomized, double blind, placebo-controlled study followed by an open label extension.

An interim Analysis will be performed when all subjects finalized the re-evaluation for retreatment visit at week 16 of the first treatment cycle or completed the double blind phase (whichever occurs earlier).

The first treatment cycle of the study will comprise two treatment groups as follows:

  • Group A (active): BoNT/A-DP (20 units, 0.5 mL)
  • Group B (placebo control): sterile, 0.9% sodium chloride, (0.5 mL). Eligible subjects will be randomized at baseline (day 0) to Group A or B to receive the first treatment in a 3:1 randomization scheme, respectively. Investigators and subjects will be blinded to the treatment administered and will evaluate the severity of glabellar lines independently. The subject should perform their assessment independently and ideally before the investigator, to ensure they are not biased by the investigator. The same investigator should assess the subject at baseline and at the visits at weeks 1, 2 and 4 in the first treatment cycle.

After a screening period of up to14 calendar days, subjects will receive the first treatment (BoNT/A-DP or placebo) and attend for visits at 1, 2 and 4 weeks after treatment and at 4 weekly intervals thereafter for evaluation of efficacy and safety (primary and key secondary efficacy endpoints are evaluated in the first treatment cycle in comparison with placebo).

The first treatment cycle will last at least 12 weeks and will end when the subjects qualify for re-treatment (in accordance with the "eligibility for re-treatment criteria"). After the first treatment cycle is completed, all subjects may enter the open label extension phase and will be dosed with BoNT/A-DP (20 U) for subsequent re-treatments.

Evaluation for re-treatment takes place at the earliest at 12 weeks after the first/previous treatment. Subjects who do not qualify for re-treatment at week 12 will have the option (pending eligibility) of re-treatment at a later visit (at 4 weekly intervals thereafter) until they are eligible for re-treatment or until a total of 48 weeks has elapsed since study start. Subjects will attend for visits at 1 and 4 weeks after any re-treatment and at 4 weekly intervals thereafter. At week 2 and week 8 of each open label cycle a telephone call visist will take place. According to the study schedule (Section 2.1 and Section 2.2), a maximum of 4 treatments per subject (4 treatment cycles) is permitted during the study time frame, with treatments separated by a minimum of 12 weeks.

The number of treatments administered per subject will depend on the subject's qualification for re-treatment; however, the last opportunity for re-treatment is at week 48.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 355 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Double Blind Phase 3 Study to Assess the Efficacy and Safety of BoNT/A-DP in the Treatment of Glabellar Lines in Comparison With Placebo Followed by an Open Label Extension Study
Actual Study Start Date : April 29, 2019
Actual Primary Completion Date : March 15, 2020
Actual Study Completion Date : December 22, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: Botulinum toxin A
Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area.
Drug: Botulinum Toxin A
Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area
Other Name: BoNT/A-DP

Placebo Comparator: Placebo
Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area.
Drug: Placebo
injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area
Other Name: sodium chloride 0,9 %

Outcome Measures
Primary Outcome Measures :
  1. Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 4 visit relative to baseline, based on both the investigators´and the subjects´ in-clinic assessments. [ Time Frame: week 4 relative to baseline ]
    The primary endpoint is the proportion of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 4 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators'and the subjects'in-clinic assessments. Thus, the primary endpoint is a composite endpoint comprising investigator and subject assessments of treatment effectiveness.


Secondary Outcome Measures :
  1. Percentage of responders at maximum frown at week 12 [ Time Frame: week 12 ]
    The percentage of responders at maximum frown at week 12 (after the first treatment with BoNT/A-DP or placebo).

  2. Percentage of responders at week 16 [ Time Frame: week 16 ]
    The percentage of responders at week 16 (after the first treatment).

  3. The proportion of subjects with a ≥ 1 point reduction in FWS score at rest at week 4 based separately on the investogators´and the subjects´ in-clinic assessments [ Time Frame: week 4 ]
    3. The proportion of subjects with a ≥ 1 point reduction in FWS score at rest at week 4 in the first treatment cycle, based separately on the investigators'and the subjects'in-clinic assessments (applicable only for subjects who have a FWS score at rest ≥ 1 at baseline).

  4. Percentage of responders at week 20 or up to week 48 [ Time Frame: week 20 ]
    The percentage of responders at week 20 or up to week 48 (after the first treatment)

  5. Frequency, severity and causal relationship of AEs, SAes and AESIs [ Time Frame: through study completion (60 weeks) ]
    Frequency, severity and causal relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) during the entire study period.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages ≥ 18 years or older at time of screening
  • Has moderate to severe glabellar fown lines at maximum frown (severity score of 2 or 3 on FWS) as determinated by in-clinic assessments by both the investigator and the subject (where: 0 =´none´, 1= ´mild´, 2= ´moderate´, 3= ´severe´).

Exclusion Criteria:

  • Any medical condition that may place the subject at increased risk due to exposure to botulinum toxin, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, profound atrophy or weakness in the target muscles, or any other condition (at the inivestigator´s discretion) that might interfere with neuromuscular function or contraindicate botulinum toxin therapy.
  • Previous treatment with any serotype of botulinum toxin for any indication within the 12 months prior to screening, or any planned treatment with botulinum toxin of any serotype for any reason during the trail (other than the investigational treatment).
  • Active skin disease/ infection or irritation at the treatment area
  • Pregnant, breastfeeding or planning to become pregnant during the trial.
Contacts and Locations

Locations
Layout table for location information
United States, Tennessee
Tennessee Clinical Research Center
Nashville, Tennessee, United States, 37215
Sponsors and Collaborators
Croma-Pharma GmbH
Investigators
Layout table for investigator information
Principal Investigator: Jeffrey Adelglass, Dr. SKINTASTIC Medical
Principal Investigator: Sue Ellen Cox, Dr. Aesthetic Solutions P.A.
Principal Investigator: Michael Gold, Dr. Tennessee Clinical Research Center
Principal Investigator: Joely Kaufman-Janette, Dr. Skin Research Institute LLC
Principal Investigator: Susan Taylor, Dr. Perelman Center for Advanced Medicine-University of Pennsylvania
Principal Investigator: Mark Nestor, Dr. Center for Clinical and Cosmetic Research
Principal Investigator: Daniel Mueller, Dr. Yuvell (Austria)
Tracking Information
First Submitted Date  ICMJE June 12, 2019
First Posted Date  ICMJE June 14, 2019
Last Update Posted Date May 19, 2021
Actual Study Start Date  ICMJE April 29, 2019
Actual Primary Completion Date March 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 4 visit relative to baseline, based on both the investigators´and the subjects´ in-clinic assessments. [ Time Frame: week 4 relative to baseline ]
The primary endpoint is the proportion of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 4 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators'and the subjects'in-clinic assessments. Thus, the primary endpoint is a composite endpoint comprising investigator and subject assessments of treatment effectiveness.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • Percentage of responders at maximum frown at week 12 [ Time Frame: week 12 ]
    The percentage of responders at maximum frown at week 12 (after the first treatment with BoNT/A-DP or placebo).
  • Percentage of responders at week 16 [ Time Frame: week 16 ]
    The percentage of responders at week 16 (after the first treatment).
  • The proportion of subjects with a ≥ 1 point reduction in FWS score at rest at week 4 based separately on the investogators´and the subjects´ in-clinic assessments [ Time Frame: week 4 ]
    3. The proportion of subjects with a ≥ 1 point reduction in FWS score at rest at week 4 in the first treatment cycle, based separately on the investigators'and the subjects'in-clinic assessments (applicable only for subjects who have a FWS score at rest ≥ 1 at baseline).
  • Percentage of responders at week 20 or up to week 48 [ Time Frame: week 20 ]
    The percentage of responders at week 20 or up to week 48 (after the first treatment)
  • Frequency, severity and causal relationship of AEs, SAes and AESIs [ Time Frame: through study completion (60 weeks) ]
    Frequency, severity and causal relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) during the entire study period.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
  • Percentage of responders at maximum frown at week 12 [ Time Frame: week 12 ]
    The percentage of responders at maximum frown at week 12 (after the first treatment with BoNT/A-DP or placebo).
  • Percentage of responders at week 16 [ Time Frame: week 16 ]
    The percentage of responders at week 16 (after the first treatment).
  • The proportion of subjects with a ≥ 1 point reduction in FWS score at rest at week 4 based separately on the investogators´and the subjects´ in-clinic assessments [ Time Frame: week 4 ]
    3. The proportion of subjects with a ≥ 1 point reduction in FWS score at rest at week 4 in the first treatment cycle, based separately on the investigators'and the subjects'in-clinic assessments (applicable only for subjects who have a FWS score at rest ≥ 1 at baseline).
  • Percentage of responders at week 20 or later [ Time Frame: week 20 ]
    The percentage of responders at week 20 or later (after the first treatment)
  • Frequency, severity and causal relationship of AEs, SAes and AESIs [ Time Frame: through study completion (60 weeks) ]
    Frequency, severity and causal relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) during the entire study period.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study III (BLESSIII)
Official Title  ICMJE Randomized Double Blind Phase 3 Study to Assess the Efficacy and Safety of BoNT/A-DP in the Treatment of Glabellar Lines in Comparison With Placebo Followed by an Open Label Extension Study
Brief Summary The aim of this study is to assess the efficacy and safety of BoNT/A-DP in the treatment of glabellar lines in comparison with placebo, including efficacy after repeat treatments and long term safety.
Detailed Description

The study is a parallel-group, randomized, double blind, placebo-controlled study followed by an open label extension.

An interim Analysis will be performed when all subjects finalized the re-evaluation for retreatment visit at week 16 of the first treatment cycle or completed the double blind phase (whichever occurs earlier).

The first treatment cycle of the study will comprise two treatment groups as follows:

  • Group A (active): BoNT/A-DP (20 units, 0.5 mL)
  • Group B (placebo control): sterile, 0.9% sodium chloride, (0.5 mL). Eligible subjects will be randomized at baseline (day 0) to Group A or B to receive the first treatment in a 3:1 randomization scheme, respectively. Investigators and subjects will be blinded to the treatment administered and will evaluate the severity of glabellar lines independently. The subject should perform their assessment independently and ideally before the investigator, to ensure they are not biased by the investigator. The same investigator should assess the subject at baseline and at the visits at weeks 1, 2 and 4 in the first treatment cycle.

After a screening period of up to14 calendar days, subjects will receive the first treatment (BoNT/A-DP or placebo) and attend for visits at 1, 2 and 4 weeks after treatment and at 4 weekly intervals thereafter for evaluation of efficacy and safety (primary and key secondary efficacy endpoints are evaluated in the first treatment cycle in comparison with placebo).

The first treatment cycle will last at least 12 weeks and will end when the subjects qualify for re-treatment (in accordance with the "eligibility for re-treatment criteria"). After the first treatment cycle is completed, all subjects may enter the open label extension phase and will be dosed with BoNT/A-DP (20 U) for subsequent re-treatments.

Evaluation for re-treatment takes place at the earliest at 12 weeks after the first/previous treatment. Subjects who do not qualify for re-treatment at week 12 will have the option (pending eligibility) of re-treatment at a later visit (at 4 weekly intervals thereafter) until they are eligible for re-treatment or until a total of 48 weeks has elapsed since study start. Subjects will attend for visits at 1 and 4 weeks after any re-treatment and at 4 weekly intervals thereafter. At week 2 and week 8 of each open label cycle a telephone call visist will take place. According to the study schedule (Section 2.1 and Section 2.2), a maximum of 4 treatments per subject (4 treatment cycles) is permitted during the study time frame, with treatments separated by a minimum of 12 weeks.

The number of treatments administered per subject will depend on the subject's qualification for re-treatment; however, the last opportunity for re-treatment is at week 48.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Glabellar Frown Lines
Intervention  ICMJE
  • Drug: Botulinum Toxin A
    Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area
    Other Name: BoNT/A-DP
  • Drug: Placebo
    injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area
    Other Name: sodium chloride 0,9 %
Study Arms  ICMJE
  • Experimental: Botulinum toxin A
    Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area.
    Intervention: Drug: Botulinum Toxin A
  • Placebo Comparator: Placebo
    Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 25, 2021)
355
Original Estimated Enrollment  ICMJE
 (submitted: June 12, 2019)
353
Actual Study Completion Date  ICMJE December 22, 2020
Actual Primary Completion Date March 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ages ≥ 18 years or older at time of screening
  • Has moderate to severe glabellar fown lines at maximum frown (severity score of 2 or 3 on FWS) as determinated by in-clinic assessments by both the investigator and the subject (where: 0 =´none´, 1= ´mild´, 2= ´moderate´, 3= ´severe´).

Exclusion Criteria:

  • Any medical condition that may place the subject at increased risk due to exposure to botulinum toxin, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, profound atrophy or weakness in the target muscles, or any other condition (at the inivestigator´s discretion) that might interfere with neuromuscular function or contraindicate botulinum toxin therapy.
  • Previous treatment with any serotype of botulinum toxin for any indication within the 12 months prior to screening, or any planned treatment with botulinum toxin of any serotype for any reason during the trail (other than the investigational treatment).
  • Active skin disease/ infection or irritation at the treatment area
  • Pregnant, breastfeeding or planning to become pregnant during the trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03985982
Other Study ID Numbers  ICMJE CPH-303-201400
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: This is not decided yet and will be changed accordingly when the decision has been made
Responsible Party Croma-Pharma GmbH
Study Sponsor  ICMJE Croma-Pharma GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey Adelglass, Dr. SKINTASTIC Medical
Principal Investigator: Sue Ellen Cox, Dr. Aesthetic Solutions P.A.
Principal Investigator: Michael Gold, Dr. Tennessee Clinical Research Center
Principal Investigator: Joely Kaufman-Janette, Dr. Skin Research Institute LLC
Principal Investigator: Susan Taylor, Dr. Perelman Center for Advanced Medicine-University of Pennsylvania
Principal Investigator: Mark Nestor, Dr. Center for Clinical and Cosmetic Research
Principal Investigator: Daniel Mueller, Dr. Yuvell (Austria)
PRS Account Croma-Pharma GmbH
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP