E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Treatment of deep furrows or frown lines in the glabellar area of the face |
|
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 | 21.1 |
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 |
|
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
20 U MT10109L and placebo for the treatment of
GL (with or without concurrent 24 U treatment of
LCL) in participants with moderate to severe GL
and LCL |
|
E.2.2 | Secondary objectives of the trial |
• To compare the efficacy between MT10109L and
placebo for the treatment of GL (with or without
concurrent treatment of LCL) in participants with
moderate to severe GL and LCL
• To compare the safety between MT10109L and
placebo for the treatment of GL (with or without
concurrent treatment of LCL) in participants with
moderate to severe GL and LCL |
|
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 glabellar lines (GL) at maximum frown (assessed by both the investigator and participant; investigator and participant ratings must be the same for GL) and bilaterally symmetrical moderate to severe LCL at maximum smile (same grade on both sides of the face as assessed by the investigator only), using the Facial Wrinkle Scale with Photonumeric Guide (FWS)
- Participants must have sufficient visual acuity without the use of eyeglasses (contact lens use acceptable) to accurately assess their facial 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 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 ophorectomy).
- Capable of giving signed informed consent as described in Appendix 1, 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.
- 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 |
|
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 glabellar lines (GL) severity using the Facial Wrinkle Scale with Photonumeric Guide (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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Coprimary: 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 modified intent-to-treat (mITT)
population after a single IM injection of
MT10109L or placebo in the GL |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
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
- 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
- The proportion of participants with = 20-point improvement from
baseline at Day 30 on the FLSQ Impact domain for GL
- 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
= 1-grade improvement from baseline at Day 30
- 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
= 1-grade improvement from baseline at Day 30
- The proportion of participants with a = 20-point improvement from
baseline at Day 30 on the 11-item Facial Line Outcomes (FLO-11)
questionnaire total score for GL
- The proportion of participants with a > 4-point improvement from
baseline at Day 30 on FLO-11 questionnaire Item 2 for GL
- The proportion of participants with a > 4-point improvement from baseline at Day 30 on FLO-11 questionnaire Item 5 for GL
- Incidence of adverse events; change from baseline in
hematology/chemistry laboratory, vital sign, and ECG parameters; and
presence of binding and neutralizing antibodies |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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 | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
Canada |
United States |
Germany |
United Kingdom |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |