A Phase I/II Study of Recombinant Botulinum Toxin Type A for the Treatment of Moderate to Severe Glabellar Lines

Study Overview
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Brief Summary
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This is a phase 1/2, multicenter, randomized, double-blind, active-controlled and placebo-controlled study to evaluate safety,immunogenicity and efficacy of YY001 for the treatment of moderate to severe glabellar lines in male and female subjects of Chinese origin. The study has been designed to test the safety,efficacy,immunogenicity of YY001,and compare to onabotulinumtoxinA (BOTOX®) and placebo, in improving the appearance of moderate to severe glabellar lines.

Official Title
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A Phase I/II,Multicenter, Randomized, Double-Blind, Placebo and Active-Controlled Study to Evaluate the Safety,Efficacy and Immunogenicity of Recombinant Botulinum Toxin Type A for the Treatment of Moderate to Severe Glabellar Lines

Conditions
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Moderate to Severe Glabellar Lines

Intervention / Treatment
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* Biological: YY001
* Biological: OnabotulinumtoxinA
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects from ≥18 to ≤65 years of age when signing an informed consent. At screening and baseline,the subject has moderate to severe GL (grade of 2 or 3 on the 4-point Scale) at maximum frown when assessed by both the Investigator and the subject. Agree to take part in the clinic trial and sign the informed consent form voluntarily. Is able to observe the protocol by Investigator's assessment. Male and female of childbearing potential agree to use a highly effective contraceptive method for the duration of the study(such as tubal ligation,abstinence,Intrauterine device,hormone,barrier method).For female of childbearing potential,her blood pregnancy test is negative within 7 days prior to study treatment,and urine pregnancy test is negative within 3 days prior to study treatment.Male can't donate the sperm within 3 months after treatment. Exclusion Criteria: Known allergy or hypersensitivity to any component of the study products(YY001 or BOTOX®). Previous use of any cosmetic therapy in the glabella or forehead area,such as hyaluronic acid,phototherapy,hydrating needle,microneedle,chemical peeling,scar removal surgery or skin dermabrasion within 6 months before screening.Previous use of biodegradable filler within 12 months before screening,such as collagen,polylactic acid or calcium hydroxyapatite.Previous use of autologous fat, any permanent products (such as silicone, polyacrylamide,no matter how long the interval is) ,face-lift,or semi-permanent prosthesis.Planned use of any cosmetic therapy in the glabella or forehead area during the study(other than the study products). Previous use of any botulinum toxin within 6 months prior to screening,or plan to use any botulinum toxin during the study(other than the study products). Use of any non-steroid anti-inflammatory drug or anticoagulant within 1 week prior to study treatment. Use of medications that affect neuromuscular transmission within 4 weeks prior to screening, such as muscle relaxant,aminoglycoside antibiotics,anticholinergic drugs,benzodiazepines,etc. Probably use of prohibited drug during the study,as assessed by the investigator. Abnormal skin at in the treatment area,scar or physical scars, in the investigator's opinion,may interfere with study evaluations. Inability to substantially spread glabellar lines apart by surgery or finger smoothing, as determined by the investigator. Ptosis,excessive facial asymmetry and skin laxity ,at screening and baseline. History of facial nerve palsy. Any medical condition that may interfere neuromuscular function including myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, dysphagia,dyspnea,diplopia,angle-closure glaucoma,eyelid or eyebrow ptosis,etc. Any concomitant disease including,unfit for the study by the investigator. In acute attack. Abnormal lab findings,and unfit for the study in the opinion of the investigator. History of alcohol or drug abuse. History of epilepsy. Any severe psychiatric illness ,in the investigator's opinion, could affect the subject's participation in the study. Female who is pregnant,or breast feeding. In any other clinical study ,or Participated in any other interventional study within 30 days or 5 half-lives prior to screening. Contract research organization,study site personnel or close relatives of the study site personnel , employees or close relatives of employees at the sponsor company. Other conditions, in the Investigator's opinion, unfit for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo and active controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Single injection with YY001 in glabellar lines | Biological: YY001<br>* Single treatment,intramuscularly injected into five sites.The total injection volume is 0.25 ml,0.05 ml per site.<br>|
| Active Comparator: Active-Controlled Group<br>Single injection with BOTOX® in glabellar lines | Biological: OnabotulinumtoxinA<br>* Single treatment,intramuscularly injected into five sites.The total injection volume is 0.25 ml,0.05 ml per site.<br>|
| Placebo Comparator: Placebo-Controlled Group<br>Single injection with placebo in glabellar lines | Biological: Placebo<br>* Single treatment,intramuscularly injected into five sites.The total injection volume is 0.25 ml,0.05 ml per site.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase1:The incidence rate of adverse events and severe adverse events within 28 days after injection |  | Within 28 days | 
| Phase1:The incidence rate of injection site reaction within 28 days after injection |  | Within 28 days | 
| Phase1:The incidence rate of abnormal lab findings which have clinical significance within 28 days after injection |  | Within 28 days | 
| Phase2:The response rate will be evaluated at 28 days by investigator at maximum frown | A response rate is defined as a subject who achieves a score of 0 or 1 in GL severity at maximum frown and at least 2 grades improvement from baseline by investigator's assessment | 28 days | 
| Phase2:The incidence rate of adverse events and severe adverse events within 12 weeks after injection |  | within 12 weeks | 
| Phase2:The incidence rate of injection site reaction within 12 weeks after injection |  | within 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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YY001, Botulinum Toxin, Glabellar Lines