Glabellar Frown LinesPhase 3BLESS-IINCT02677805
Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study II
A Phase 3 study testing Botulinum Toxin A and Botulinum Toxin A - Open Label in people with Glabellar Frown Lines, run by Croma-Pharma GmbH at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Glabellar Frown Lines
- What is being tested?
- Botulinum Toxin A and Botulinum Toxin A - Open Label
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 251 participants
- Where
- 7 sitesUnited States
- Study dates
- 30 Mar 2016to 3 Nov 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥ 18 years or older at time of screening on FWS) as determined by in-clinic assessments by both the investigator and the subject(where: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe').
- Subject has a stable medical condition with no uncontrolled systemic disease.
- Female subjects of childbearing potential must test negative for pregnancy and agree to use effective birth control during the course of the study.
- Subjects who wear glasses must be able to adequately self-assess the severity of their glabellar lines (according to the FWS), without glasses obstructing the forehead area.
- The moderate to severe glabellar lines have an important psychological impact on the subject, as indicated by scores >0 on either the Emotional or the Social Functioning subscale of the modified Skindex-16 (GL-QoL).
Who cannot join
- 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 trial (other than the investigational treatment).
- Known hypersensitivity to the study medication or its excipients.
- 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 investigator's discretion) that might interfere with neuromuscular function or contraindicate botulinum toxin therapy.
- Facial laser or light treatment, microdermabrasion, superficial peels or retinoid therapy within the 3 months prior to screening or planned during the study.
- Apart from the procedures specified above, previous treatment with any facial aesthetic procedure in the glabellar area (including chemical peeling, injection with biodegradable fillers,) within 12 months prior to screening or planned during the study.
- Previous insertion of permanent material in the glabellar area or planned during the study.
Show all 27Show fewer
- Any surgery, or history of surgery, in the glabellar area including surgical removal of the corrugator, procerus or depressor supercili muscles or a combination of these, or scars in the glabellar area, or such surgery planned during the study.
- Active skin disease/infection or irritation at the treatment area.
- Inability to substantially lessen glabellar frown lines even by physically spreading them apart.
- Use of a muscle relaxant, , within 2 weeks prior to screening or planned during the study.
- Marked facial asymmetry or ptosis of eyelid and/or eyebrow, or current facial palsy or neuromuscular junction disorders as judged by the investigator.
- Pregnant, breastfeeding or planning to become pregnant during the trial.
- Use of prohibited medication including anticholinergic drugs, or drugs which could interfere with neuromuscular function, including aminoglycoside antibiotics and curare-like compounds within 2 weeks prior to screening or planned during the study.
- Planned surgery with general anaesthetic (use of local anaesthetic outside the glabellar area is permitted).
- Participation in another clinical study within one month of screening and throughout the trial.
- Previous participation in another botulinum toxin aesthetic study which involved the treatment of glabellar lines in combination with canthal lines and/or forehead lines in the previous 18 months.
- Chronic drug or alcohol abuse (as per investigator discretion).
- Eligibility Criteria for re-treatment: The following criteria MUST be met for re-treatment:
- At time of re-treatment subject does not have relevant changes to their health status from enrollment, which would have prevented subject's entry into the study according to the inclusion and exclusion criteria
- The subject must have been randomized to receive treatment and must have received at least one treatment (BoNT/A-DP or placebo).
- A minimum of 12 weeks must have elapsed since the previous study treatment.
- The subject's glabellar lines at maximum frown must have relapsed to a FWS score of 2 or 3 as determined by the investigator and the subject.
- No relevant infection or inflammation in the planned injection area.
- Negative urine pregnancy test, in women of child-bearing potential.
- The subject must have received fewer than four study treatments.
- The subject must agree and consent to re-treatment.
- Re-treatment will be performed at the latest by week 48.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Center for Clinical and Cosmetic Research
Aventura, Florida, 33180
California Dermatology & Clinical Research Institute
Encinitas, California, 92024
Skin Laser And Surgery Specialists Of New York & New Jersey
Hillsborough, New Jersey
The Center for Dermatology, Cosmetic & Laser Surger
Mount Kisco, New York
Lorenc Aesthetic Plastic Surgery Center
New York, New York
Skintastic Medical
Plano, Texas, 75093
Holcomb Kreithen Plastic Surgery
Sarasota, Florida
About this study
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
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.
Read the detailed description
This multicenter Phase 3 study is comprised of two parts. The first part of the study is a randomized, double blind, placebo-controlled, phase which aims to demonstrate efficacy and safety of BoNT/A-DP compared with placebo. The second part is an open label extension phase to evaluate efficacy after repeat treatments and long term safety. Subjects can receive a maximum of four treatment cycles over the duration of the study, a single treatment in the first cycle compared with placebo, and up to three subsequent treatments in the open label extension study.
- Conditions
- Glabellar Frown Lines
- Being tested
- Botulinum Toxin A, Placebo, Botulinum Toxin A - Open Label
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum Toxin ADrug
Also called BoNT/A-DP
Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area
PlaceboDrug
Also called sodium chloride 0.9 %
injection, sodium chloride 0.9% divided in five 0.1 mL i.m. injections into the glabellar area
Botulinum Toxin A - Open LabelDrug
Also called BoNT/A-DP
Open Label Extension Phase with Experimental Drug; Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area
| Study group | Role | What they receive |
|---|---|---|
| Botulinum toxin A | Experimental | 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. Receives: Drug: Botulinum Toxin A |
| Placebo | Placebo comparator | Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Receives: Drug: Placebo |
| Botulinum toxin A open label extension phase | Experimental | Open Label Extension Phase for all Subjects of Arm 1 and 2 for up to 3 treatment cycles Receives: Drug: Botulinum Toxin A - Open Label |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
The primary endpoint is the percentage 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. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 4
Secondary outcomes (24)
Percentage of Responders at Maximum Frown at Week 12
Percentage 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 12 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 12
Percentage of Responders at Maximum Frown at Week 16
Percentage 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 16 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 16
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest at Week 4 Based Separately on the Investigators' and the Subjects' In-clinic Assessments
The Percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (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). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 4
Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32
Percentage 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 the respective visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 20, Week 24, Week 28, Week 32
Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines)
Extent of change in psychological impact at week 4 after first treatment, relative to baseline, assessed by
- modified Skindex-16 (Glabellar Line Quality of Life Scale, [GL-QoL]): Each of 7 items rated on 5-point scale: 0/Never, 1/Rarely, 2/Sometimes, 3/Often, 4/Always bothered, than rescaled to a 0 to 100 standardized score; Emotional Domain is the mean of 4 of the items; Social Functioning Domain is the mean of 3 of the items; Overall score is the mean of all 7 items. All reported scores ranging from 0 (best outcome) to 100 (worst outcome).
- validated FACE-Q Appraisal of Lines Between Eyebrows scale: Each of 7 items rated on 4-point scale: 1/Not at all, 2/a little, 3/moderately, 4/extremely. Reported score is the sum of the 7 items, standardized on a scale from 0 (worst outcome) to 100 (best outcome).
- Age Appraisal visual analog scale [VAS]: Perception of Age compared to actual age, in years ranging from -15 years (best outcome) to +15 years (worst outcome).
Measured: Week 4
Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8
The Percentage of responders among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score at maximum frown of 0 or 1 and an improvement ≥ 2 points in FWS score (at maximum frown) during the first treatment cycle visit relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint, at weeks 1, 2 and 8). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 1, Week 2, Week 8
Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs
The percentage of subjects with ≥ 2-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle visit relative to baseline, based on the independent raters' assessment of photographs (at baseline and visits 2, 4, 12, 16 and 20 weeks after treatment, within the first treatment cycle). The median value of all assessments of the same photography was considered for analysis. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 2, Week 4, Week 12, Week 16, Week 20
Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle
Time to onset of effect in the BoNT/A-DP and placebo groups in the first treatment cycle, as measured at weeks 1, 2 and 4 based separately on subject and investigator assessment. Onset of effect defined as at least a 1 point improvement in Facial Wrinkle Scale (FWS) score from baseline (at maximum frown). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: From treatment at Day 0 to Week 4 in Treatment Cycle 1
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale
The extent of subject perceptions of effect of, and satisfaction with, treatment in the BoNT/A-DP and placebo groups, during each treatment cycle, as assessed by the validated FACE-Q Satisfaction with Outcome Scale. The FACE-Q Satisfaction with Outcome scale is a patient-reported outcome measure designed to assess a patient's satisfaction with the results of a facial aesthetic procedure. This scale comprises six items, each with four response options: "definitely agree", "somewhat agree", "somewhat disagree", and "definitely disagree".
Measured: Week 4 of Treatment Cycles 1, 2, 3 and 4
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs
The Percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest in the BoNT/A-DP and placebo groups, relative to baseline, during the first treatment cycle, based on the independent raters' assessment of photographs. The median value of all assessments of the same photography was considered for analysis. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 2, Week 4, Week 12, Week 16, Week 20, Week 24, Week 28
Percentage of Subjects With a Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at 4 Weeks After Re-treatment Relative to the Rating at the Preceding End-of-Cycle Visit
The percentage of subjects with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at 4 weeks after re-treatment relative to the rating at the preceding end-of-cycle visit, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
Measured: Week 4 of Treatment Cycles 2, 3 and 4
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs)
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.
Measured: Through study completion (60 weeks)
Number of Participants With Neutralizing Anti-Drug Antibodies
Number of Participants with Neutralizing Anti-Drug Antibodies Antibody formation, evaluation pre-dose before each treatment, at 4 weeks after each treatment and at the final study visit.
Measured: Through study completion (60 weeks)
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase
Safety assessments by evaluating change from baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase as per the study schedule
Measured: Week 4 of each treatment cycle
Change From Baseline of Bilirubin, Creatinine
Safety assessments by evaluating change from baseline of Bilirubin, Creatinine as per the study schedule as change from baseline
Measured: Week 4 of each treatment cycle
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen
Safety assessments by evaluating change from baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen as per the study schedule
Measured: Week 4 of each treatment cycle
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
Safety assessments by evaluating change from baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets as per the study schedule
Measured: Week 4 of each treatment cycle
Change From Baseline of Erythrocytes
Safety assessments by evaluating change from baseline of Erythrocytes as per the study schedule
Measured: Week 4 of each treatment cycle
Change From Baseline of Erythrocyte MCHC, Hemoglobin
Safety assessments by evaluating change from baseline of Erythrocyte MCHC, Hemoglobin as per the study schedule
Measured: Week 4 of each treatment cycle
Change From Baseline of of Erythrocyte MCV
Safety assessments by evaluating change from baseline of Erythrocyte MCV as per the study schedule
Measured: Week 4 of each treatment cycle
Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes
Safety assessments by evaluating change from baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes as per the study schedule as change from baseline
Measured: Week 4 of each treatment cycle
Change From Baseline of Systolic and Diastolic Blood Pressure
Safety assessments by evaluating change from baseline of Systolic and Diastolic Blood Pressure as per the study schedule
Measured: Week 4 of Treatment Cycles 1, 2, 3 and 4
Change From Baseline of Pulse Rate
Safety assessments by evaluating change from baseline of Pulse rate as per the study schedule
Measured: Week 4 of Treatment Cycles 1, 2, 3 and 4
Number of Participants With Normal and Abnormal Electrocardiogram
Safety assessments by evaluating Electrocardiogram as per the study schedule
Measured: Last visit of Treatment Cycle 1 (End of Cycle procedures) conducted upon confirmation of eligibility for retreatment, which was assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a maximum of 48 weeks post treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2016 (estimated)
- Study start30 Mar 2016
- Primary completion15 Sep 2016
- Study completion3 Nov 2017
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 Glabellar Frown LinesStudies of the same condition, open and under way.
- 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
- 251 participants (actual)
Sponsor and investigators
- Lead sponsor
- Croma-Pharma GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02677805
- Sponsor's protocol ID
- CPH-302-201030
- Acronym
- BLESS-II
- Status last verified
- May 2022
- First submitted
- 4 Feb 2016
- Last updated
- 19 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cox SE, Kaufman-Janette J, Cohen JL, Gold M, Joseph J, Nestor MS, Rzany B, Taylor S, Zhou J, Cecerle M, Pueraro E, Irvine R, Dayan S. LetibotulinumtoxinA Attenuates the Psychological Burden of Glabellar Lines and Is Associated With High Subject Satisfaction in Phase 3 Clinical Trials. Dermatol Surg. 2024 Jun 1;50(6):535-541. doi: 10.1097/DSS.0000000000004152. Epub 2024 Mar 12.
PubMed 38470985
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02677805
- Acronym / sponsor ID
- BLESS-II / CPH-302-201030
- Conditions
- Glabellar Frown Lines
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 251 participants (actual)
- Lead sponsor
- Croma-Pharma GmbHIndustry (pharma, biotech, devices)
- Study start
- 30 Mar 2016 (actual)
- Primary completion
- 15 Sep 2016 (actual)
- Study completion
- 3 Nov 2017 (actual)
- First posted
- 9 Feb 2016 (estimated)
- Results
- Posted 19 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
This multicenter Phase 3 study is comprised of two parts. The first part of the study is a randomized, double blind, placebo-controlled, phase which aims to demonstrate efficacy and safety of BoNT/A-DP compared with placebo. The second part is an open label extension phase to evaluate efficacy after repeat treatments and long term safety. Subjects can receive a maximum of four treatment cycles over the duration of the study, a single treatment in the first cycle compared with placebo, and up to three subsequent treatments in the open label extension study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Botulinum toxin A | Experimental | Drug: Botulinum Toxin ABotulinum 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. |
| Botulinum toxin A open label extension phase | Experimental | Drug: Botulinum Toxin A - Open LabelOpen Label Extension Phase for all Subjects of Arm 1 and 2 for up to 3 treatment cycles |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged ≥ 18 years or older at time of screening on FWS) as determined by in-clinic assessments by both the investigator and the subject(where: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe').
- Subject has a stable medical condition with no uncontrolled systemic disease.
- Female subjects of childbearing potential must test negative for pregnancy and agree to use effective birth control during the course of the study.
- Subjects who wear glasses must be able to adequately self-assess the severity of their glabellar lines (according to the FWS), without glasses obstructing the forehead area.
- The moderate to severe glabellar lines have an important psychological impact on the subject, as indicated by scores >0 on either the Emotional or the Social Functioning subscale of the modified Skindex-16 (GL-QoL).
Key exclusion criteria (27 listed)
- 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 trial (other than the investigational treatment).
- Known hypersensitivity to the study medication or its excipients.
- 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 investigator's discretion) that might interfere with neuromuscular function or contraindicate botulinum toxin therapy.
- Facial laser or light treatment, microdermabrasion, superficial peels or retinoid therapy within the 3 months prior to screening or planned during the study.
- Apart from the procedures specified above, previous treatment with any facial aesthetic procedure in the glabellar area (including chemical peeling, injection with biodegradable fillers,) within 12 months prior to screening or planned during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Botulinum Toxin AAlso: BoNT/A-DPInjection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area | Drug | Botulinum toxin A |
| PlaceboAlso: sodium chloride 0.9 %injection, sodium chloride 0.9% divided in five 0.1 mL i.m. injections into the glabellar area | Drug | Placebo |
| Botulinum Toxin A - Open LabelAlso: BoNT/A-DPOpen Label Extension Phase with Experimental Drug; Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area | Drug | Botulinum toxin A open label extension phase |
Primary outcome
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
The primary endpoint is the percentage 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. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.
24 secondary outcomes
Percentage of Responders at Maximum Frown at Week 12
Time frame: Week 12
Percentage of Responders at Maximum Frown at Week 16
Time frame: Week 16
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest at Week 4 Based Separately on the Investigators' and the Subjects' In-clinic Assessments
Time frame: Week 4
Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32
Time frame: Week 20, Week 24, Week 28, Week 32
Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines)
Time frame: Week 4
Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8
Time frame: Week 1, Week 2, Week 8
Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs
Time frame: Week 2, Week 4, Week 12, Week 16, Week 20
Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle
Time frame: From treatment at Day 0 to Week 4 in Treatment Cycle 1
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale
Time frame: Week 4 of Treatment Cycles 1, 2, 3 and 4
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs
Time frame: Week 2, Week 4, Week 12, Week 16, Week 20, Week 24, Week 28
Percentage of Subjects With a Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at 4 Weeks After Re-treatment Relative to the Rating at the Preceding End-of-Cycle Visit
Time frame: Week 4 of Treatment Cycles 2, 3 and 4
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs)
Time frame: Through study completion (60 weeks)
Number of Participants With Neutralizing Anti-Drug Antibodies
Time frame: Through study completion (60 weeks)
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase
Time frame: Week 4 of each treatment cycle
Change From Baseline of Bilirubin, Creatinine
Time frame: Week 4 of each treatment cycle
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen
Time frame: Week 4 of each treatment cycle
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
Time frame: Week 4 of each treatment cycle
Change From Baseline of Erythrocytes
Time frame: Week 4 of each treatment cycle
Change From Baseline of Erythrocyte MCHC, Hemoglobin
Time frame: Week 4 of each treatment cycle
Change From Baseline of of Erythrocyte MCV
Time frame: Week 4 of each treatment cycle
Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes
Time frame: Week 4 of each treatment cycle
Change From Baseline of Systolic and Diastolic Blood Pressure
Time frame: Week 4 of Treatment Cycles 1, 2, 3 and 4
Change From Baseline of Pulse Rate
Time frame: Week 4 of Treatment Cycles 1, 2, 3 and 4
Number of Participants With Normal and Abnormal Electrocardiogram
Time frame: Last visit of Treatment Cycle 1 (End of Cycle procedures) conducted upon confirmation of eligibility for retreatment, which was assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a maximum of 48 weeks post treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38470985Cox SE, Kaufman-Janette J, Cohen JL, Gold M, Joseph J, Nestor MS, Rzany B, Taylor S, Zhou J, Cecerle M, Pueraro E, Irvine R, Dayan S. LetibotulinumtoxinA Attenuates the Psychological Burden of Glabellar Lines and Is Associated With High Subject Satisfaction in Phase 3 Clinical Trials. Dermatol Surg. 2024 Jun 1;50(6):535-541. doi: 10.1097/DSS.0000000000004152. Epub 2024 Mar 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Botulinum Toxin A and Botulinum Toxin A - Open Label in people with Glabellar Frown Lines, run by Croma-Pharma GmbH at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02677805, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2025.