Moderate to Severe Glabellar Lines
Conditions
Brief summary
The purpose of this study is to assess the effectiveness and safety of IPN10200 compared to placebo in the improvement of the appearance of moderate to severe glabellar lines in adult participants. Glabellar lines are wrinkle-like lines that appear between the eyebrows and can become more noticeable with age or repeated facial expressions. They may affect a person's appearance and confidence. In this study, all participants will receive a single injection of either IPN10200 or placebo (the study drug). There will be 3 periods in this study: * A screening period (up to 20 days) to assess whether the participant can take part, requiring at least 1 visit to the study centre. * A treatment period (Day 1) where all the eligible participants will receive a single injection of IPN10200 or placebo. * A follow-up period (52 weeks) where participants' health will be monitored, consisting of regular visits to the study centre and 1 telephone call visit. Participants will undergo health measurements and observation, including blood sampling, physical examinations, clinical evaluations and electrocardiograms (ECG: recording of the electrical activity of heart). They will also be asked to fill in questionnaires and keep a diary. Each participant will be in this study for up to 55 weeks. Participants may withdraw consent to participate at any time.
Interventions
BIOLOGICALIPN10200
A single vial of lyophilised powder for solution for injection will be injected locally into several sites across the glabellar region.
BIOLOGICALPlacebo
A single vial of lyophilised powder for solution, containing excipients without active substance, will be injected locally into several sites across the glabellar region.
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participant should be male or female, ≥18 years of age inclusive at the time of signing the ICF. * Moderate or severe (Grade 2 or 3) GL at MF at baseline, as assessed by the ILA using a validated 4-point photographic scale. * Moderate or severe (Grade 2 or 3) GL at MF at baseline, as assessed by the SSA using a 4-point categorical scale. * Dissatisfied or very dissatisfied (Grade 2 or 3) with their lines at baseline, as assessed by the SLS. * For female participants: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. * Participant has both the time and the ability to complete the study and comply with study instructions. * Does not reside in an institution by administrative or court order. * Is not a sponsor employee or clinical research unit personnel directly affiliated with the study or is not an immediate family member. Immediate family is defined as a spouse, parent, child or sibling whether biological or legally adopted.
Exclusion criteria
* An active infection or other skin problems in the upper face including the GL area (e.g. acute acne lesions or ulcers). * A history of eyelid blepharoplasty or brow lift or any other upper facial surgery within the past 5 years. * A history of facial nerve palsy. * Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring or thick sebaceous skin. * Presence of any scars, piercings or tattoos (including micro blading of the eyebrows) in or around the treatment area that have occurred within 6 months prior to baseline, or which in the investigator's opinion, could interfere with evaluations. * Any known medical condition that may put the participant at increased risk in regard to exposure to BoNT of any serotype (i.e. myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, etc.). * Administration of any BoNT (other than the study intervention on baseline visit) into any site of the body and for any indication from 9 months prior to the first study visit until the end of the study. * Participants who have received IPN10200 in a previous study. * Use of medications that affect neuromuscular transmission (such as curare-like nondepolarising agents, lincosamides, polymyxins, anticholinesterases) within the past 30 days prior to baseline are prohibited or a longer washout period of at least five half-lives might be required, as deemed appropriate by the investigator for long-acting medications. * Use of aminoglycoside antibiotics within the past 30 days prior to baseline are prohibited. Note: Topical use apart from the area of injection would be acceptable. * Use of systemic retinoids within the past 30 days prior to baseline and planned use during the study. Note: Topical retinoids are allowed other than in the areas that will be injected (upper facial area) at the discretion of the investigator. * Any prior treatment with permanent fillers, lifting threads, autologous fat or permanent procedures in the upper face including the GL area. * Administration of any non-permanent injectables (such as hyaluronic acid, calcium hydroxylapatite, poly-L-Lactic acid or polymethyl-methacrylate) soft tissue augmentation therapy in the GL region within 12 months prior to baseline. * Any prior facial treatment or aesthetic procedures to the upper face including photo rejuvenation, vascular or pigment laser or microneedling within the 3 months prior to baseline. * Any prior facial treatment or aesthetic procedures to the upper face involving skin resurfacing (including dermabrasion, laser or whatever the interventional technique used) or chemical peel within the past 12 months prior to baseline. * Any planned cosmetic surgery or aesthetic procedures to the upper face during the study and/or any procedures to other parts of the face which in the investigator's opinion, could interfere with evaluations during the study. * Any past surgery in the UFL area including GL. * Planned use of concomitant therapy which, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study intervention. Therapy considered necessary for the participant's welfare may be given at the discretion of the investigator. Note: If the permissibility of a specific medication/treatment is in question, the medical monitor will be contacted. * Use of any experimental device within 30 days prior to baseline visit or use of any treatment with an experimental drug within five times the documented terminal half-life of the respective drug or its metabolites or if the half-life is unknown within 30 days prior to the start of the study (prior to baseline visit) and during the conduct of the study. * Known positive for hepatitis B antigen, hepatitis C virus antibody or for human immunodeficiency virus or a diagnosis of acquired immunodeficiency syndrome. * Clinically diagnosed significant anxiety disorder, or any other significant psychiatric disorder (e.g. depression) that might interfere with the participant's participation in the study. * An inability to substantially lessen GL as determined by the investigator. * Known allergy or hypersensitivity to BoNT or any excipients of IPN10200. * A history of chronic or recreational drug abuse as assessed by the investigator. * Any uncontrolled systemic disease or other significant medical condition which would be harmful for the participant to be entered into the study or continue participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| For North America: Percentage of participants responding to treatment | From baseline to week 4 | Measured by the multicomponent response of ≥2-grade improvement from baseline and a score of 'None' or 'Mild' on Investigator's Live Assessment (ILA) and Subject's Self-Assessment (SSA) at maximum frown ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." SSA: a 4-point categorical scale used to assess the appearance of glabellar lines at maximum frown, where grade 0 = "No wrinkles," grade 1 = "Mild wrinkles," grade 2 = "Moderate wrinkles," and grade 3 = "Severe wrinkles. |
| For EU and ROW: Percentage of participants responding to treatment | From baseline to week 4 | Measured by a ≥2-grade improvement on Investigator's Live Assessment (ILA)at maximum frown ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| For North America: Percentage of participants responding to treatment | At week 24 | Measured by the multicomponent response of ≥2-grade improvement from baseline and a score of 'None' or 'Mild' on Investigator's Live Assessment (ILA) and Subject's Self-Assessment (SSA) at maximum frown. ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." SSA: a 4-point categorical scale used to assess the appearance of glabellar lines at maximum frown, where grade 0 = "No wrinkles," grade 1 = "Mild wrinkles," grade 2 = "Moderate wrinkles," and grade 3 = "Severe wrinkles. |
| For EU and ROW: Response to treatment as measured by a score of 'None' or 'Mild' at Week 4 on the ILA at maximum frown | At week 24 | ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
| Percentage of participants responding to treatment as measured by a score of "None" or "Mild on ILA at maximum frown | At week 24 | ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
| Percentage of participants responding to treatment as measured by a score of "None" or "Mild on SSA at maximum frown | At week 24 | SSA: a 4-point categorical scale used to assess the appearance of glabellar lines at maximum frown, where grade 0 = "No wrinkles," grade 1 = "Mild wrinkles," grade 2 = "Moderate wrinkles," and grade 3 = "Severe wrinkles. |
| For all regions except United States: Percentage of participants satisfied with their facial appearance after the treatment as measured by a score of 'Very Satisfied' or 'Satisfied' on Subject's Level of Satisfaction (SLS) | At week 4 | SLS: a 4-point categorical scale used to assess satisfaction with the appearance of glabellar lines, where grade 0 = "Very satisfied," grade 1 = "Satisfied," grade 2 = "Dissatisfied," and grade 3 = "Very dissatisfied." |
| For all regions except United States: Number of participants satisfied with their facial appearance after the treatment as measured by a score of 'Very Satisfied' or 'Satisfied' on SLS | At week 24 | SLS: a 4-point categorical scale used to assess satisfaction with the appearance of glabellar lines, where grade 0 = "Very satisfied," grade 1 = "Satisfied," grade 2 = "Dissatisfied," and grade 3 = "Very dissatisfied." |
| For EU: Response as measured by an improvement of ≥ 10 points from baseline on the Rasch Transformed Score of the FACE-Q Psychological Function Scale | At week 4 | FACE-Q Psychological Function Scale: a validated 4-point categorical scale used to assess participants' psychological well-being. The scale consists of statements about how participants feel about themselves, with responses indicating the level of agreement on a 4-point scale ranging from "strongly disagree" to "strongly agree." |
| Percentage of participants responding to treatment | From baseline to each post-treatment visit until week 52 (up to 1 year), (except week 4 and 24 for North America) | Measured by the multicomponent response of 2-grade improvement and a score of 'None or 'Mild' on both the ILA and SSA at maximum frown. ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." SSA: a 4-point categorical scale used to assess the appearance of glabellar lines at maximum frown, where grade 0 = "No wrinkles," grade 1 = "Mild wrinkles," grade 2 = "Moderate wrinkles," and grade 3 = "Severe wrinkles. |
| Percentage of participants responding to treatment as measured by the response of 2-grade improvement on ILA at maximum frown | From baseline to each post-treatment visit until Week 52 (up to 1 year) (except Week 4 for EU and ROW) | ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
| Percentage of participants responding to treatment as measured by the response of 2-grade improvement on SSA at maximum frown | From baseline to each post-treatment visit until Week 52 (up to 1 year) | SSA: a 4-point categorical scale used to assess the appearance of glabellar lines at maximum frown, where grade 0 = "No wrinkles," grade 1 = "Mild wrinkles," grade 2 = "Moderate wrinkles," and grade 3 = "Severe wrinkles. |
| Percentage of participants responding to treatment as measured by the response of 1-grade improvement on ILA at maximum frown | From baseline to each post-treatment visit until Week 52 (up to 1 year) | ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
| Percentage of participants responding to treatment as measured by the response of 1-grade improvement on SSA at maximum frown | From baseline to each post-treatment visit until Week 52] (up to 1 year) | SSA: a 4-point categorical scale used to assess the appearance of glabellar lines at maximum frown, where grade 0 = "No wrinkles," grade 1 = "Mild wrinkles," grade 2 = "Moderate wrinkles," and grade 3 = "Severe wrinkles. |
| Percentage of participants responding to treatment as measured by the response of 1-grade improvement on ILA at rest | From baseline to each post-treatment visit until Week 52 (up to 1 year) | ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at rest, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
| Percentage of participants satisfied with their facial appearance after the treatment as measured by a score of 'Very Satisfied' or 'Satisfied' on SLS | From baseline to each post-treatment visit until Week 52 (up to 1 year), (except Week 4 and 24 for all regions except United States) | SLS: a 4-point categorical scale used to assess satisfaction with the appearance of glabellar lines, where grade 0 = "Very satisfied," grade 1 = "Satisfied," grade 2 = "Dissatisfied," and grade 3 = "Very dissatisfied." |
| Percentage of participants answering 'Improved', 'Much Improved' or 'Very Much Improved', as measured by Global Aesthetic Improvement Scale (GAIS) at maximum frown | At week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 (up to 1 year) | GAIS: a validated 7-point categorical scale used to assess global aesthetic improvement in appearance compared to pretreatment, as determined by the participant at maximum frown, where grade -3 = "Very much worse," grade -2 = "Much worse," grade -1 = "Worse," grade 0 = "No change," grade 1 = "Improved," grade 2 = "Much improved," and grade 3 = "Very much improved." |
| Percentage of participants answering 'Improved', 'Much Improved' or 'Very Much Improved', as measured by GAIS at rest | At week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 (up to 1 year) | GAIS: a validated 7-point categorical scale used to assess global aesthetic improvement in appearance compared to pretreatment, as determined by the participant at rest, where grade -3 = "Very much worse," grade -2 = "Much worse," grade -1 = "Worse," grade 0 = "No change," grade 1 = "Improved," grade 2 = "Much improved," and grade 3 = "Very much improved." |
| Percentage of clinicians answering 'Improved', 'Much Improved' or 'Very Much Improved', as measured by Global Aesthetic Improvement Scale (GAIS) at maximum frown | At week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 (up to 1 year) | GAIS: a validated 7-point categorical scale used to assess global aesthetic improvement in appearance compared to pretreatment, as determined by the clinician at maximum frown, where grade -3 = "Very much worse," grade -2 = "Much worse," grade -1 = "Worse," grade 0 = "No change," grade 1 = "Improved," grade 2 = "Much improved," and grade 3 = "Very much improved." |
| Percentage of clinicians answering 'Improved', 'Much Improved' or 'Very Much Improved', as measured by Global Aesthetic Improvement Scale (GAIS) at rest | At week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 (up to one year) | GAIS: a validated 7-point categorical scale used to assess global aesthetic improvement in appearance compared to pretreatment, as determined by the clinician with the participant at rest, where grade -3 = "Very much worse," grade -2 = "Much worse," grade -1 = "Worse," grade 0 = "No change," grade 1 = "Improved," grade 2 = "Much improved," and grade 3 = "Very much improved." |
| Percentage of participants with change from baseline in psychological function, as measured by Psychological Well-Being Scale on FACE-Q | At baseline, week 1, 2, 4 (except the EU), 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 (up to 1 year) | FACE-Q Psychological Function Scale: a validated 4-point categorical scale used to assess participants' psychological well-being. The scale consists of statements about how participants feel about themselves, with responses indicating the level of agreement on a 4-point scale ranging from "strongly disagree" to "strongly agree." |
| Time to onset of treatment response based on subject diary to evaluate the appearance of their lines | At baseline and daily from Day 1 to Day 8 (Week 1) | Participants record in a diary whether they notice an improvement in the appearance of their glabellar lines, with responses captured as Yes/No. |
| Time taken for a responder to re-exhibit their baseline severity grade on the ILA at maximum frown | At all timepoints post-injection (Day 1) until end of study (up to 1 year) | Responder is defined as having a score of 'None' or 'Mild' on the ILA. ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
| Time taken for a responder to re-exhibit a severity grade of 'Moderate' or 'Severe' as measured by the ILA at maximum frown | At all timepoints post-injection (Day 1) until end of study (up to 1 year) | Responder is defined as having a score of 'None' or 'Mild' on the ILA. ILA: a validated 4-point photographic scale used to assess the severity and appearance of glabellar lines at maximum frown, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
| Percentage of participants experiencing treatment emergent adverse events (TEAEs) | At all timepoints post-injection (Day 1) until end of study (up to 1 year) | An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE is an AE for which the start date is on or after the date that the intervention began. |
| Percentage of participants experiencing serious adverse events (SAEs) | At all timepoints post-injection (Day 1) until end of study (up to 1 year) | A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, or is considered medically significant by the investigator. |
| Percentage of participants experiencing Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs) | At all timepoints post-injection (Day 1) until end of study (up to 1 year) | An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE is an AE for which the start date is on or after the date that the intervention began. Adverse events of special interest (AESIs) are AEs that may not be serious but are of special importance to a particular drug or class of drugs. |
| Percentage of participants with clinically significant changes from baseline in vital signs | At all timepoints post-injection (Day 1) until end of study (up to 1 year) | Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator. |
| Percentage of participants with clinically significant change from baseline in 12-lead Electrocardiogram (ECG) readings | At week 4 and week 52 | — |
| Percentage of participants with clinically significant change from baseline in facial examination | At all timepoints post-injection (Day 1) until end of study (up to 1 year) | Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator. |
| Percentage of participants with binding antibodies to IPN10200 | At screening, week 4, 12, 24, 36 and 52 (up to 1 year 1 month) | — |
| Percentage of participants with neutralising antibodies to IPN10200 | At screening, week 4, 12, 24, 36 and 52 (up to 1 year 1 month) | — |
Countries
Canada, United States
Contacts
CONTACTIpsen Recruitment Enquiries
STUDY_DIRECTORIpsen Medical Director
Ipsen
Outcome results
None listed