E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of Glabellar Lines (GL) - deep furrows or frown lines in the glabellar area of the face |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052609 |
E.1.2 | Term | Glabellar frown lines |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy between 24 U MT10109L and placebo for the treatment of GL in participants with moderate to severe GL |
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E.2.2 | Secondary objectives of the trial |
• To compare the efficacy between MT10109L and placebo for the treatment of GL in participants with moderate to severe GL
• To compare the safety between MT10109L and placebo for the treatment of GL in participants with moderate to severe GL |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must be ≥ 18 years of age and considered to be an adult in her/his local jurisdiction at the time of signing the informed consent.
- Moderate to severe GL at maximum frown (as assessed by both the investigator and participant; investigator and participant ratings must be the same) using the FWS.
- Participants must have sufficient visual acuity without the use of eyeglasses (contact lens use acceptable) to accurately assess their GL lines, in the opinion of the investigator.
- Male and female
- Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period.
- Female participants of childbearing potential must have a negative urine pregnancy test before each study intervention. A female is considered NOT to be of childbearing potential if she is premenarchal, postmenopausal (at least 12 consecutive months without menstruation), or permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral oophorectomy).
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Written informed consent from the participant has been obtained prior to any study-related procedures.
- Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable. (eg, Written Authorization for Use and Release of Health and Research Study Information [US sites] and written Data Protection consent [EU sites]).
- Ability to follow study instructions, including completing study assessment tools without any assistance or alteration to the assessment tools and likely to complete all required visits. |
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E.4 | Principal exclusion criteria |
- Any condition which precludes a participant’s ability to comply with study requirements, including completion of the study visits or inability to read, understand, and/or self-assess GL severity using FWS.
- Known immunization or hypersensitivity to any botulinum toxin serotype.
- Any medical condition that may put the participant at increased risk with exposure to MT10109L including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other condition that might interfere with neuromuscular function.
- Any history of significant cardiovascular disease, family history of long QT syndrome, or a clinically significant electrocardiogram (ECG) abnormality at the Screening Visit.
- Marked facial asymmetry, dermatochalasis, deep dermal scarring, excessively thick sebaceous skin, or the inability to substantially lessen facial lines even by physically spreading them apart, as determined by the investigator.
- Any brow or eyelid ptosis, as determined by the investigator.
- Infection or skin disorder at the injection sites.
- History of facial nerve palsy.
- Any uncontrolled systemic disease.
- Recent history of alcohol or drug abuse based on the investigator’s judgment
- Anticipated need for treatment with botulinum toxin of any serotype for any reason during the study (other than study intervention).
- Anticipated need for surgery or overnight hospitalization during the study.
- Prior exposure to botulinum toxin of any serotype for any reason
- Any of the following procedures or treatments occurring in the specified period before enrollment (Day 1):
- 3 months: any facial nonablative resurfacing laser, light or ultrasound treatment, microdermabrasion, or superficial peels
- 6 months: any facial cosmetic procedure with medium depth or deep depth chemical peels (eg, trichloroacetic acid [TCA] and phenol); periorbital, mid-facial, or upper-facial skin resurfacing; or permanent make-up in the mid-facial (extending from inferior orbital margin to level of the nasal base) or upper facial areas
- 12 months: any periorbital, mid-facial, or upper-facial treatment with nonpermanent soft tissue fillers
- Participants on topical retinoid therapy and/or topical hormone cream applied to the face, who have not been on a consistent dose regimen for at least 6 months before enrollment and who are unable to maintain the same regimen for the study.
- Participants on oral retinoid therapy within 1 year before study enrollment.
- Prior periorbital surgery, facial lift (full face or mid-face), thread lift, brow lift, or related procedures (eg, eyelid [blepharoplasty] and/or eyebrow surgery).
- Prior facial treatment with permanent soft tissue fillers, synthetic implantation (eg, Gore-Tex®), and/or autologous fat transplantation.
- Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study.
- Females who are pregnant, nursing, or planning a pregnancy during the study.
- Participants who plan for an extended absence away from the immediate area of the study site that would preclude them from returning for all protocol specified study visits.
- Participants who, in the investigator’s opinion, are unable or unwilling to maintain their standardized skin care regimen throughout the study period.
- The participant has a condition or is in a situation which, in the investigator’s opinion, may put the participant at significant risk, may confound the study results, or may interfere significantly with the participant’s participation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of participants achieving a rating of none or mild on the FWS according to investigator and participant assessments of GL severity at maximum frown at Day 30 using the mITT population after a single IM injection of MT10109L or placebo in the GL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Secondary: The duration of GL treatment effect estimated as the median time to return to moderate or severe GL at maximum frown in participants who achieved a rating of none or mild GL severity at maximum frown at Day 30 according to investigator assessments using the FWS
• Secondary: The proportion of participants reporting mostly satisfied/very satisfied on a 5-point scale of very dissatisfied to very satisfied at Day 60 on the FLSQ follow-up version Item 5 for GL
• Secondary: The proportion of participants with ≥ 20-point improvement from baseline at Day 30 on the FLSQ Impact domain for GL
• Secondary: The proportion of responders for investigator assessments of GL severity at rest using the FWS among participants who were rated at least mild at rest at baseline, where a responder is defined as achieving a ≥ 1-grade improvement from baseline at Day 30
• Secondary: The proportion of responders for participant assessments of GL severity at rest using the FWS among participants who were rated at least mild at rest at baseline, where a responder is defined as achieving a ≥ 1-grade improvement from baseline at Day 30
• Secondary: The proportion of participants with a ≥ 20-point improvement from baseline at Day 30 on the FLO-11© questionnaire total score for GL
• Secondary: The proportion of participants with a > 4-point improvement from baseline at Day 30 on FLO-11 questionnaire Item 2 for GL
• Secondary: The proportion of participants with a > 4-point improvement from baseline at Day 30 on FLO-11 questionnaire Item 5 for GL
• Secondary: Incidence of adverse events; change from baseline in vital sign and ECG parameters; and presence of binding and neutralizing antibodies |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open label during the retreatment period |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |