Study to Compare 2 Botulinum Type A Toxins in the Treatment of Glabellar Frown Lines

Phase 2

Completed

Conditions: Frown Lines

Interventions: Biological: Botulinum toxin A "BoNT/A-DP"
Biological: Botulinum toxin A "Botox Cosmetics"

Registration Number: NCT04763265

Lead Sponsor: Croma-Pharma GmbH

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 208

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A (n=100): BoNT/A-DP (20 U, 0.5 mL)	Botulinum toxin A "BoNT/A-DP"	The injection sites should be prepared according to standard clinical procedures.. A volume of 0.5 mL of the properly reconstituted BoNT/A-DP should be drawn into the sterile syringe and any air bubbles in the syringe barrel expelled. The needle used to reconstitute the product should be removed and replaced with a sterile insulin or tuberculin-type syringe of 1 mL volume with 0.01 mL graduation and with the gauge range of 30 to 33 G, which the investigator routinely uses for toxin administration. Each subject will receive a total of five i.m. injections of 4 U/0.1 mL (total of 20 U).
Group B (n=100): Botox Cosmetic (20 U, 0.5 mL)	Botulinum toxin A "Botox Cosmetics"	The injection sites should be prepared according to standard clinical procedures. A volume of 0.5 mL of the properly reconstituted Botox Cosmetic should be drawn into the sterile syringe and any air bubbles in the syringe barrel expelled. The needle used to reconstitute the product should be removed and replaced with a sterile insulin or tuberculin-type syringe of 1 mL volume with 0.01 mL graduation and with the gauge range of 30 to 33 G, which the investigator routinely uses for toxin administration. Each subject will receive a total of five i.m. injections of 4 U/0.1 mL (total of 20 U).

Primary Outcome Measures

Name	Time	Method
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.	week 4	The primary endpoint is the percentage of subjects among BoNT/A-DP and Botox Cosmetic groups with a 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 (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. Subjects with missing in-clinic assessments with the FWS at Baseline or Week 4 were assigned as non-responders.

Secondary Outcome Measures

Name	Time	Method
FACE-Q Satisfaction With Outcome Scale Based on Subject Assessment at Weeks 4, 12 and 16 Satisfaction With Outcome Scale.	Weeks 4, 12 and 16	Summary of FACE-Q satisfaction with outcome scale based on subject assessment at weeks 4, 12 and 16 after a single treatment and compared to Botox Cosmetic. 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."
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	Weeks 1, 2, 8, 12 and 16	The percentage of responders based on the independent investigator assessment and subject assessment at Weeks 1, 2, 8, 12 and 16 after a single treatment with BoNT/A-DP and compared to a single treatment of Botox Cosmetic. Responder is defined as having a Facial Wrinkle Scale (FWS) score of 0 or 1 and at least 1 point reduction in FWS score at maximum frown over Baseline, on the 4-point FWS. FWS scores are ranked as 0 (no facial wrinkles), 1 (mild facial wrinkles), 2 (moderate facial wrinkles) and 3 (severe facial wrinkles). Subjects with missing in-clinic assessments with the FWS at Baseline or the respective visit were assigned as non-responders.
Change From Baseline in Blood Pressure at Weeks 1, 4, 12 and 16	Weeks 1, 4, 12, and 16	Summary of change from baseline in diastolic/systolic blood pressure at weeks 1, 4, 12 and 16 after a single treatment and compared to Botox Cosmetic.
Change From Baseline in Pulse Rate at Weeks 1, 4, 12 and 16	Weeks 1, 4, 12, and 16	Summary of change from baseline in pulse rate at weeks 1, 4, 12 and 16 after a single treatment and compared to Botox Cosmetic.
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	Weeks 1, 2, 4, 8, 12 and 16	The percentage of responders based on the independent investigator assessment and subject assessment at Weeks 1, 2, 4, 8, 12 and 16 after a single treatment with BoNT/A-DP and compared to a single treatment of Botox Cosmetic. Responder is defined as having a Facial Wrinkle Scale (FWS) score of 0 or 1 and at least 2 point reduction in FWS score at maximum frown over Baseline, on the 4-point FWS. FWS scores are ranked as 0 (no facial wrinkles), 1 (mild facial wrinkles), 2 (moderate facial wrinkles) and 3 (severe facial wrinkles). Subjects with missing in-clinic assessments with the FWS at Baseline or the respective visit were assigned as non-responders.
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	Weeks 1, 2, 4, 8, 12 and 16	The percentage of responders based on the independent investigator assessment and subject assessment at Weeks 1, 2, 4, 8, 12 and 16 after a single treatment with BoNT/A-DP and compared to a single treatment of Botox Cosmetic. Responder is defined as having a Facial Wrinkle Scale (FWS) score of 0 or 1 and at least 1 point reduction in FWS score at rest over Baseline, on the 4-point FWS. FWS scores are ranked as 0 (no facial wrinkles), 1 (mild facial wrinkles), 2 (moderate facial wrinkles) and 3 (severe facial wrinkles). Subjects with missing in-clinic assessments with the FWS at Baseline or the respective visit were assigned as non-responders.
Time to Onset of Effect Based on Independent Investigator Assessment and Subject Assessment	From treatment at Day 0 to Week 4	Time to onset of effect in days, as measured at Weeks 1, 2, and 4, based on independent investigator and subject assessments after a single treatment with BoNT/A-DP and compared to Botox Cosmetic. Onset of effect is defined as at least 1 point improvement in Glabellar Line Scale - Investigator (GLS-I) and Glabellar Line Scale - Subject (GLS-S) score relative to Baseline at maximum frown in glabellar lines. GLS-I and GLS-S both use the same 4-point scale, ranked as 0 (No lines/minimal lines), 1 (Mild lines), 2 (Moderate lines) and 3 (Severe lines).
Duration of Effect Based on Independent Investigator Assessment and Subject Assessment	16 Weeks	For subjects who are responders at week 4, duration of effect in days is assessed based on independent investigator and subject assessments after a single treatment with BoNT/A-DP and compared to Botox Cosmetic. Responder is defined as having a Facial Wrinkle Scale (FWS) score of 0 or 1 and at least 1 point reduction in FWS score at maximum frown over Baseline, on the 4-point FWS. FWS scores are ranked as 0 (no facial wrinkles), 1 (mild facial wrinkles), 2 (moderate facial wrinkles) and 3 (severe facial wrinkles). Effect is deemed to be lost when scores return to Baseline or worse values. Duration of effect is defined as (the date that loss of response occurred) - (date of single study treatment ) + 1.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs)	through study completion, an average of 16 weeks	Frequency, seriousness and severity of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest (AESIs), as well as causal relationship to the study medication and the study procedure, during the entire study period. A subject with multiple occurrences of an adverse event is counted only once within the worst severity category.

Trial Locations

Locations (5): Sweat Clinics of Canada
🇨🇦
Toronto, Ontario, Canada
Skin Research Institute LLC
🇺🇸
Coral Gables, Florida, United States
ATS Clinical Research
🇺🇸
Santa Monica, California, United States
Monika Sulovsky
🇦🇹
Vienna, Austria
Institute Of Cosmetic
🇨🇦
Oakville, Ontario, Canada