A Phase 3 Multicenter Study to Evaluate the Safety and Efficacy of AGN-151586 for the Treatment of Glabellar Lines in Toxin-Naïve Subjects
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 309
- Locations
- 17
- Primary Endpoint
- Percentage of Participants With a Grade 0 or 1 and a ≥ 2-grade Improvement From Baseline on the FWS According to Both Investigator and Subject Assessments of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [US FDA]
Study Overview
Brief Summary
Facial lines that develop from repeated facial expression, such as glabellar lines (GL), are typically treated by selectively weakening specific muscles with small quantities of botulinum toxin. AGN-151586 is an investigational product being developed for the treatment of GL. The purpose of this study is to evaluate the safety and efficacy of AGN-151586 for the treatment of GL in toxin-naïve participants with moderate to severe GL.
This is a 12 week study in which eligible subjects will be enrolled into the study containing 2 treatment periods, double-blind period and open-label period. Participants are randomly assigned to receive AGN-151586 or placebo. There is 1 in a 4 chance that participants will receive placebo. Around 300 adult participants with moderate to severe GL will be enrolled in the study in approximately 15 sites.
Participants will receive either AGN-151586 or Placebo administered as 5 intramuscular injections to the glabellar complex on Day 1. Participants meeting retreatment criteria may receive an open-label treatment of AGN-151586 during the study.
Participants will attend regular visits during the study at a study site. The effect of the treatment will be checked by medical assessments, blood tests, telephone calls, questionnaires and checking for side effects.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants must be able to accurately assess their facial lines without the use of eyeglasses (contact lens use is acceptable).
- •Participant must have moderate or severe Glabellar Lines at maximum frown as assessed by both the investigator and participant using the Facial Wrinkle Scale (FWS) at Screening and Baseline Day 1 visit.
Exclusion Criteria
- •Uncontrolled systemic disease.
- •Participants must not have a history of any use of botulinum neurotoxin of any serotype for any indication (including any investigational botulinum neurotoxin product).
- •Presence or history of any medical condition that may place the participant at increased risk following exposure to AGN-151586 or interfere with the study evaluation, including:
- •Diagnosed myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function
- •History of facial nerve palsy
- •Infection or dermatological condition at the treatment injection sites
- •Marked facial asymmetry, dermatochalasis, deep dermal scarring, excessively thick sebaceous skin, excessively photodamaged skin, or the inability to substantially lessen facial lines even by physically spreading them apart
- •Any eyebrow or eyelid ptosis at screening or Baseline Day 1 visit as determined by the investigator
- •History of known immunization to any botulinum neurotoxin serotype.
- •Tattoos, jewelry, or clothing which obscure the glabellar area and cannot be removed.
- •Anticipated need for surgery or overnight hospitalization during the study.
- •History of surgical procedures on forehead and/or periorbital areas or affecting these areas including any lifting procedure (e.g., rhinoplasty, facial lift, suture lift, thread lift, brow lift, eyelid and/or eyebrow surgery).
- •History of periorbital, mid-facial, or upper-facial treatment with semi permanent or permanent soft tissue fillers (e.g., poly-L-lactic acid, polyalkylimide, polymethylmethacrylate, polytetrafluoroethylene, and silicone), synthetic implantation and/or autologous fat transplantation.
- •Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
- •Female subject who is pregnant or breastfeeding, and is considering becoming pregnant or donating eggs during the study or for approximately 30 days after the last dose of study drug or until the end of study, whichever is longer.
- •Participant who has been treated with any investigational drug within 30 days of the drug prior to the first dose of study drug or is currently enrolled in another clinical study or was previously enrolled in this study.
- •Anticipated need for treatment with botulinum neurotoxin of any serotype for any reason during the study (other than study drug).
Arms & Interventions
AGN-151586
Participants will receive 5 intramuscular injections of AGN-151586 in the glabellar complex on Day 1. Based on meeting the retreatment criteria, the participant may also receive 1 open-label treatment of AGN-151586.
Intervention: AGN-151586 (Drug)
Placebo
Participants will receive 5 intramuscular injections of Placebo in the glabellar complex on Day 1. Based on meeting the retreatment criteria, the participant may also receive 1 open-label treatment of AGN-151586.
Intervention: AGN-151586 (Drug)
Placebo
Participants will receive 5 intramuscular injections of Placebo in the glabellar complex on Day 1. Based on meeting the retreatment criteria, the participant may also receive 1 open-label treatment of AGN-151586.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With a Grade 0 or 1 and a ≥ 2-grade Improvement From Baseline on the FWS According to Both Investigator and Subject Assessments of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [US FDA]
Time Frame: Baseline, Day 7 (Double-blind period)
\[Primary endpoint for the United States FDA\] Percentage of participants achieving a Grade 0 or 1 (none or mild) and a ≥ 2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to both investigator and participant assessments of glabellar lines (GL) severity at maximum frown at Day 7 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal.
Percentage of Participants With a ≥ 2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]
Time Frame: Baseline, Day 7 (Double-blind period)
\[Primary endpoint for European Union regulatory agencies\] Percentage of participants with a ≥ 2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to participant assessment of glabellar lines (GL) severity at maximum frown at Day 7 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal.
Percentage of Participants With a ≥ 2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]
Time Frame: Baseline, Day 7 (Double-blind Period)
\[Primary endpoint for European Union regulatory agencies\] Percentage of participants with a ≥ 2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to investigator assessment of glabellar lines (GL) severity at maximum frown at Day 7 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal.
Number of Participants With Adverse Events
Time Frame: From time of informed consent to end of study; median time on follow-up was 85 days for all groups.
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.
Secondary Outcomes
- Percentage of Participants With a Grade 0 or 1 and a ≥ 2-grade Improvement From Baseline on the FWS According to Both Investigator and Participant Assessments of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA](Baseline, Hours 8, 12, 24, 36, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period))
- Percentage of Participants With a Grade 0 or 1 and a ≥ 2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA](Baseline, Hours 8, 12, 24, 36, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period))
- Percentage of Participants With a Grade 0 or 1 and a ≥ 2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA](Baseline, Hours 8, 12, 24, 36, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period))
- Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Day 7 [US FDA](Day 7 (Double-blind Period))
- Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Hour 24 [United States FDA](Hour 24 (Double-blind Period))
- Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [US FDA](Day 7 (Double-blind Period))
- Percentage of Participants With a ≥ 20-point Improvement From Baseline in FLO-11 Total Scores for GL at Day 7 [European Union Regulatory Agencies](Baseline, Day 7 (Double-blind Period))
- Percentage of Participants With a ≥ 2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies](Baseline, Hour 24 (Double-blind Period))
- Percentage of Participants With a ≥ 2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies](Baseline, Hour 24 (Double-blind Period))
- Percentage of Participants With a ≥ 1-grade Improvement From Baseline on FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies](Baseline, Hour 24 (Double-blind Period))
- Percentage of Participants With a ≥ 1-grade Improvement From Baseline on FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies](Baseline, Hour 24 (Double-blind Period))
- Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Hour 24 [European Union Regulatory Agencies](Hour 24 (Double-blind Period))
- Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [European Union Regulatory Agencies](Day 7 (Double-blind Period))
- Percentage of Participants With a ≥ 4-point Improvement From Baseline in FLO-11 Item 10 (Look Angry) for GL at Day 7 [European Union Regulatory Agencies](Day 7 (Double-blind Period))
- Percentage of Participants With a ≥ 4-point Improvement From Baseline in FLO-11 Item 5 (Look Less Attractive) for GL at Day 7 [European Union Regulatory Agencies](Baseline, Day 7 (Double-blind Period))