Moderate to Severe Glabellar Lines
Conditions
Brief summary
The purpose of this study is to assess the effectiveness and safety of a single dose of IPN10200 compared to placebo (double-blind phase) and how well and safely repeat doses of IPN10200 work over time (open-label phase) in adult participants with moderate to severe glabellar lines. 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. All participants in the double-blind phase will receive IPN10200 or placebo during the first treatment cycle. De novo participants in the open-label phase will receive IPN10200 during the first treatment cycle. Some participants may receive additional treatment cycles with IPN10200 depending on their eligibility. 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 where participants may receive up to 4 treatment cycles. In the double-blind phase, participants receive a single treatment of IPN10200 or placebo. In the open-label phase (rollover participants from double-blind), eligible participants may receive additional cycles of IPN10200. In the open-label phase (de novo participants), participants will receive IPN10200 in the first cycle and eligible participants may receive additional cycles of IPN10200. Requires multiple visits during the first month followed by 1 visit every month. * A follow-up period (24 weeks) after the last injection where participants' health will be monitored. 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 107 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 at the time of signing the informed consent. * 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. * Are 'dissatisfied' or 'very dissatisfied' with their GLs at baseline, as assessed by the SLS score. * 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 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. * Closed-angle glaucoma or a predisposition to it (for Japan only). * Any known medical condition that may put the participant at increased risk with regard to exposure to BoNT of any serotype (i.e. myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, etc.). * Presence of any scars, piercings, or tattoos (including microblading 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. * Administration of any BoNT (other than the study intervention) 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. * Treatment with IPN10200 in any prior 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 is 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 nonpermanent injectables (such as hyaluronic acid, calcium hydroxylapatite, poly-L-lactic acid or polymethyl-methacrylate) for 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 photorejuvenation, 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 upper facial line 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 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) and during the conduct of the study. * Known positive for hepatitis B antigen, or 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 | At week 4 | Measured by the multi-component response of ≥2-grade improvement 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 as measured by ≥2-grades improvement on the ILA at maximum frown | From baseline to week 4 | 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 Double Blind (DB) phase: For North America: Percentage of participants responding to treatment | At week 24 | Measured by the composite response of ≥2-grade improvement and a score of 'None' or 'Mild' on ILA and SSAat 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 DB phase: Percentage participants responding to treatment as measured by a score of "None" or "Mild on ILA at maximum frown | At each post-treatment visit except week 4 (For EU and ROW) and week 24 (for United States) up to 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." |
| For DB phase: 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 DB phase: 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 and week 24 | SLS: a validated 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 DB and Open Label (OL) phase: Percentage of participants responding to treatment as measured by a score of "None" or "Mild" on ILA at maximum frown | DB phase: From baseline to each post-treatment visit until week 52 (except week 4 (for EU and all other regions) and week 24); OL phase: From baseline to each post-treatment visit until week 104 | 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." |
| For DB and OL phase: Percentage of participants responding to treatment as measured by a score of "None" or "Mild" on SSA at maximum frown | DB phase: From baseline to each post-treatment visit until week 52 (except week 24); OL phase: From baseline to each post-treatment visit until week 104 | 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 DB and OL phase: Percentage of participants responding to treatment | From baseline to each post-treatment visit until week 52 (except week 4 and week 24 [for North America]); OL phase: From baseline to each post-treatment visit until week 104 | Measured by the multi-component response of ≥2-grade improvement and a score of 'None' or 'Mild' on 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." |
| For DB and OL phase: Percentage of participants responding to treatment as measured by the response of ≥2-grade improvement and a score of 'None' or 'Mild' on ILA at maximum frown | From baseline to each post-treatment visit until week 52 (except week 4 and week 24 [for North America]); OL phase: From baseline to each post-treatment visit until week 104 | 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." |
| For DB and OL phase: Percentage of participants responding to treatment as measured by the response of ≥2-grade improvement and a score of 'None' or 'Mild' on SSA at maximum frown | DB phase: From baseline to each post-treatment visit until week 52; OL phase: From baseline to each post-treatment visit until week 104 | 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 DB and OL phase: Percentage of participants responding to treatment as measured by the response of ≥1-grade improvement on ILA at maximum frown | DB phase: From baseline to each post-treatment visit until week 52; OL phase: From baseline to each post-treatment visit until week 104 | 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." |
| For DB and OL phase: 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; OL phase: From baseline to each post-treatment visit until week 104 | 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 DB and OL phase: Percentage of participants responding to treatment as measured by the response of ≥1-grade improvement on ILA at rest | DB phase: From baseline to each post-treatment visit until week 52; OL phase: From baseline to each post-treatment visit until week 104 | LA: 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." |
| For DB and OL phase: Percentage of participants satisfied with their facial appearance after the treatment as measured by a score of 'Very Satisfied' or 'Satisfied' on SLS | DB phase: From baseline to each post-treatment visit until week 52 (except week 4 and week 24 [for United States]); OL phase: From baseline to each post-treatment visit until week 104 | SLS: a validated 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 DB and OL phase: Percentage of participants with change from baseline in ageing appearance, as measured by visual analogue scale (VAS) on FACE-Q | DB phase: For each post-treatment visit until end of DB phase (week 52); OL phase: From baseline to all visits until end of OL phase (week 104) | FACE-Q Ageing Appearance VAS: a validated visual analogue scale used to assess participants' perceived age compared with their actual age. Participants respond to the question, "How many years younger or older do you think you look compared with your actual age?" by selecting a point on the scale, where negative values indicate years younger and positive values indicate years older |
| For DB and OL phase: Percentage of participants with an improvement of at least 10 points from baseline on the Rasch Transformed Score of the FACE-Q Psychological Function Scale | DB phase: From baseline to all visits until end of DB phase (week 52) (except at week 4 for EU); OL phase: From baseline to all visits until end of OL phase (week 104) | 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 "definitely disagree" to "definitely agree." |
| For DB phase: Time to onset of treatment response based on participant diary to evaluate the appearance of their lines | From 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. |
| For OL phase: Time between two consecutive injections | OL phase: 24 weeks after the previous injections until week 80 | — |
| For DB phase: Time taken for a responder to re-exhibit a severity grade of 'Moderate' or 'Severe' on the ILA at maximum frown | At all timepoints post-injection until end of DB phase (week 52). | 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 rest, where grade 0 = "None," grade 1 = "Mild," grade 2 = "Moderate," and grade 3 = "Severe." |
| For DB and OL phase: Percentage of participants experiencing treatment emergent adverse events (TEAEs). | DB phase: At all timepoints post-injection until end of DB phase (week 52); OL phase: At all timepoints post-injection until end of OL phase (week 104) | 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. |
| For DB and OL phase: Percentage of participants experiencing serious adverse events (SAEs). | DB phase: At all timepoints post-injection until end of DB phase (week 52); OL phase: At all timepoints post-injection until OL phase (week 104) | 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. |
| For DB and OL phase: Percentage of participants experiencing Adverse Events (AEs) (or SAEs) leading to withdrawals and Adverse Events of Special Interest (AESIs). | At all timepoints post-injection until end of DB phase (week 52); OL phase: At all timepoints post-injection until OL phase (week 104) | 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. |
| For DB and OL phase: Percentage of participants with clinically significant changes from baseline in vital signs. | At all timepoints post-injection until end of DB phase (week 52); OL phase: At all timepoints post-injection until OL phase (week 104) | Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator. |
| For DB and OL phase: Percentage of participants with clinically significant Change from baseline in 12-lead Electrocardiogram (ECG) readings | DB phase: At baseline, week 4 and 52; OL phase: Up to week 104 | — |
| For DB and OL phase: Percentage of participants with clinically significant change from baseline in facial and focused neurological/physical examination | DB phase: At all timepoints post-injection until end of DB phase (week 52); OL phase: At all timepoints post-injection until OL phase (week 104) | Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator. |
| For DB and OL phase: Percentage of participants with binding antibodies to IPN10200 | DB phase: At screening, week 4, 12, 24, 36, 52, & EoS; OL phase: At baseline, week 4, 12, 24, 36, 52 of each cycle & EoS. Cycle 1 is up to 1 year for DB & 18 months for OL, Cycle 2 up to 1 year 1 month, Cycle 3 up to 8 months, and Cycle 4 up to 6 months | — |
| For DB and OL phase: Percentage of participants with neutralising antibodies to IPN10200 | DB phase: At screening, week 4, 12, 24, 36, 52, & EoS; OL phase: At baseline, week 4, 12, 24, 36, 52 of each cycle & EoS. Cycle 1 is up to 1 year for DB & 18 months for OL, Cycle 2 up to 1 year 1 month, Cycle 3 up to 8 months, and Cycle 4 up to 6 months | — |
Countries
France, Germany, Japan, United States
Contacts
CONTACTIpsen Recruitment Enquiries
Outcome results
None listed