Clinical trial NCT04763265: Study to Compare 2 Botulinum Type A Toxins in the Treatment of Glabellar Frown Lines
Official title: A Double-Blinded, Randomized, Controlled Study to Compare the Efficacy, Time to Onset, and Duration of Effect of Botulinum Type A Toxins in the Treatment of Glabellar Frown Lines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Frown Lines
Lead sponsor: Croma-Pharma GmbH
Sponsor class: INDUSTRY
Collaborators: name: Hugel
First posted: 2021-02-21
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, randomized, double-blind, comparator-controlled study. The study will take place in the EU, US and Canada. The benefit of participation in this study is the expected reduction in the severity of glabellar frown lines. All subjects will benefit from free medical screenings and follow up.
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to provide preliminary comparative data on BoNT/A-DP versus Botox Cosmetic. Subsequently the sample size is primarily based on clinical judgement and practical considerations.

Detailed description: This will be a multi-center, randomized, double-blind, comparator-controlled study. The study will take place in the EU, US and Canada.

To allow all subjects to profit from treatment and to obtain adequate data for BoNT/A DP treatment, the study will be comprised of a double-blinded treatment comparing BoNT/A-DP with Botox Cosmetic (ratio 1:1). Primary and secondary endpoints will compare efficacy, safety and subject satisfaction after a single treatment of the investigational BoNT/A DP to an existing commercially available product (Botox Cosmetic).

Two hundred subjects will be enrolled, which should allow for a precise estimate of response rate and for post-hoc sensitivity analyses.

The duration of study participation for each subject will be up to 18 weeks, to include screening (maximum of 2 weeks; re-screening will not be permitted), and a single treatment (comprised of one injection at five injection points) of BoNT/A-DP (Group A) or Botox Cosmetic (Group B) followed by six efficacy and safety follow-up visits. A total of 200 subjects will be randomized 1:1 to Group A or Group B at Baseline. Both investigators and subjects will be blinded to treatment. Investigators and subjects will evaluate the severity of glabellar lines independently.

Eligibility criteria: Inclusion Criteria:• Has moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on GLS-I/GLS-S) 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 highly 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 GLS-S), without glasses obstructing the forehead area.

Exclusion Criteria:

* 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 study (other than the investigational treatment).
* Known hypersensitivity to either 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 three months prior to Screening or planned during the study.

  o Apart from the procedures specified above, previous treatment with any facial aesthetic procedure in the glabellar area (including chemical peeling, injection with biodegradable fillers, photo rejuvenation) within 12 months prior to Screening or planned during the study.
* Previous insertion of permanent material in the glabellar area, or planned insertion during the study.
* Any planned or history of surgery in the glabellar area and/or canthal line area, or scars in the glabellar and/or canthal line.
* Active skin disease/infection or irritation at the treatment area.
* Inability to substantially lessen glabellar frown lines and or lateral canthal lines even by physically spreading them apart.
* Use of a muscle relaxant within 2 weeks prior to Screening, or planned use 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 study.
* 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 anesthetic (use of local anesthetic outside the glabellar area is permitted).
* Participation in another clinical study within one month of Screening and throughout the study.
* 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).

Primary outcomes:
measure: Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 1 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.
timeFrame: week 4
Secondary outcomes:
measure: Responder Status (With a Facial Wrinkle Scale (FWS) Score of 0 or 1 and at Least 1 Point Reduction at Maximum Frown) Based on Independent Investigator Assessment and Subject Assessment at Weeks 1, 2, 8, 12 and 16
timeFrame: Weeks 1, 2, 8, 12 and 16
measure: Responder Status (With a Facial Wrinkle Scale (FWS) Score of 0 or 1 and at Least 2 Point Reduction at Maximum Frown) Based on Independent Investigator Assessment and Subject Assessment at Weeks 1, 2, 4, 8, 12 and 16
timeFrame: Weeks 1, 2, 4, 8, 12 and 16
measure: Responder Status (With a Facial Wrinkle Scale (FWS) Score of 0 or 1 and at Least 1 Point Reduction at Rest) Based on Independent Investigator Assessment and Subject Assessment at Weeks 1, 2, 4, 8, 12 and 16
timeFrame: Weeks 1, 2, 4, 8, 12 and 16
measure: Time to Onset of Effect Based on Independent Investigator Assessment and Subject Assessment
timeFrame: From treatment at Day 0 to Week 4
measure: Duration of Effect Based on Independent Investigator Assessment and Subject Assessment
timeFrame: 16 Weeks
measure: FACE-Q Satisfaction With Outcome Scale Based on Subject Assessment at Weeks 4, 12 and 16 Satisfaction With Outcome Scale.
timeFrame: Weeks 4, 12 and 16
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs)
timeFrame: through study completion, an average of 16 weeks
measure: Change From Baseline in Blood Pressure at Weeks 1, 4, 12 and 16
timeFrame: Weeks 1, 4, 12, and 16
measure: Change From Baseline in Pulse Rate at Weeks 1, 4, 12 and 16
timeFrame: Weeks 1, 4, 12, and 16
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: ATS Clinical Research
state: California
city: Coral Gables
country: United States
facility: Skin Research Institute LLC
state: Florida
city: Vienna
country: Austria
facility: Monika Sulovsky
city: Oakville
country: Canada
facility: Institute Of Cosmetic
state: Ontario
city: Toronto
country: Canada
facility: Sweat Clinics of Canada
state: Ontario
Study officials:
References: