Trial Outcomes & Findings for MT10109L in the Treatment of Lateral Canthal Lines (NCT NCT03785145)

NCT ID: NCT03785145

Last Updated: 2023-10-05

Results Overview

The primary efficacy measure is a composite endpoint and a participant is considered responder only if both the investigator and participant independently report a ≥ 2-grade improvement at Day 30 of Double-Blind Period from baseline. Both participant and investigator used FWS to assess GL severity. FWS is 4-grade scale (0 to 3): 0=none, 1=mild, 2=moderate and 3=severe

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 235 participants
• Primary outcome timeframe: Day 30
• Results posted on: 2023-10-05

Participant Flow

235 met the inclusion/exclusion criteria and were randomized. 234 participants entered the study and were treated. This note is to explain why the number of participants to start a Period is not equal to the number who completed previous Period: Only participants who met the retreatment criteria received additional treatments (up to 2 times) in open label period. Therefore, the total number of treatments was different for each participant.

Participant milestones

Measure	Placebo During Double-blind/MT10109L During Open-label Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Double-blind portion: Placebo was injected into the LCL. Open-label portion: In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L injections	MT10109L During Double-blind/MT10109L During Open-label MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. Double-blind portion: MT10109L was injected into the LCL. Open-label portion: Participants who met retreatment criteria were allowed up to 2 additional MT10109L injections
Cycle 1 - Double Blind (Days 1-180) STARTED	77	158
Cycle 1 - Double Blind (Days 1-180) COMPLETED	68	145
Cycle 1 - Double Blind (Days 1-180) NOT COMPLETED	9	13
Cycle 2 - Open Label Treatment 1 STARTED	65	144
Cycle 2 - Open Label Treatment 1 COMPLETED	61	130
Cycle 2 - Open Label Treatment 1 NOT COMPLETED	4	14
Cycle 3 - Open Label Treatment 2 STARTED	49	91
Cycle 3 - Open Label Treatment 2 COMPLETED	49	88
Cycle 3 - Open Label Treatment 2 NOT COMPLETED	0	3

Reasons for withdrawal

Measure	Placebo During Double-blind/MT10109L During Open-label Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Double-blind portion: Placebo was injected into the LCL. Open-label portion: In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L injections	MT10109L During Double-blind/MT10109L During Open-label MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. Double-blind portion: MT10109L was injected into the LCL. Open-label portion: Participants who met retreatment criteria were allowed up to 2 additional MT10109L injections
Cycle 1 - Double Blind (Days 1-180) Adverse Event	0	1
Cycle 1 - Double Blind (Days 1-180) Withdrawal by Subject	6	9
Cycle 1 - Double Blind (Days 1-180) Lost to Follow-up	2	2
Cycle 1 - Double Blind (Days 1-180) Death	0	1
Cycle 1 - Double Blind (Days 1-180) 1 participant was randomized to the placebo group but was not treated. This is counted in 'Other '.	1	0
Cycle 2 - Open Label Treatment 1 Withdrawal by Subject	1	5
Cycle 2 - Open Label Treatment 1 Lost to Follow-up	1	6
Cycle 2 - Open Label Treatment 1 COVID-19; Enrolled in a different study	2	3
Cycle 3 - Open Label Treatment 2 Withdrawal by Subject	0	1
Cycle 3 - Open Label Treatment 2 Lost to Follow-up	0	1
Cycle 3 - Open Label Treatment 2 COVID-19, Enrolled in a different study	0	1

Baseline Characteristics

MT10109L in the Treatment of Lateral Canthal Lines

Baseline characteristics by cohort

Measure	Placebo n=77 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=158 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.	Total n=235 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	75 Participants n=5 Participants	149 Participants n=7 Participants	224 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	46.1 Years STANDARD_DEVIATION 11.09 • n=5 Participants	46.6 Years STANDARD_DEVIATION 11.43 • n=7 Participants	46.4 Years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	127 Participants n=7 Participants	188 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	31 Participants n=7 Participants	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	33 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=5 Participants	125 Participants n=7 Participants	192 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	74 Participants n=5 Participants	145 Participants n=7 Participants	219 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 30

Population: All primary and secondary efficacy analyses endpoints were carried out using the Intent-To-Treat (ITT) analysis set, which was defined as all participants who were randomized. Multiple imputation method was used for missing variables in primary efficacy endpoint. Analyses of the secondary efficacy variables were performed using observed data.

The primary efficacy measure is a composite endpoint and a participant is considered responder only if both the investigator and participant independently report a ≥ 2-grade improvement at Day 30 of Double-Blind Period from baseline. Both participant and investigator used FWS to assess GL severity. FWS is 4-grade scale (0 to 3): 0=none, 1=mild, 2=moderate and 3=severe

Outcome measures

Measure	Placebo n=77 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=158 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
The Percentage of Participants With a ≥ 2-grade Improvement From Baseline on the Facial Wrinkle Scale With Photonumeric Guide (FWS) According to INVESTIGATOR AND PARTICIPANT Assessments of Lateral Canthal Lines (LCL) Severity at Maximum Smile at Day 30	2 Participants	48 Participants

SECONDARY outcome

Timeframe: Day 30

Population: All secondary efficacy analyses endpoints were carried out using the Intent-To-Treat (ITT) analysis subset at day 30, which was defined as all participants who were randomized. Analyses of the secondary efficacy variables were performed using observed data.

The Percentage of Responders for Investigator Assessments of Lateral Canthal Lines (LCL) Severity at Maximum Smile Using the Facial Wrinkle Scale (FWS), where a Responder was defined as Achieving a≥2-grade Improvement from Baseline at Maximum Smile at Day 30.

The investigator evaluates the participant's LCL severity using a 4-point scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3=severe.

Outcome measures

Measure	Placebo n=72 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=147 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
The Percentage of Responders for INVESTIGATOR Assessments of Lateral Canthal Lines (LCL) Severity at Maximum Smile Using the Facial Wrinkle Scale (FWS)	3 Participants	57 Participants

SECONDARY outcome

Timeframe: Day 1 (first treatment) to Day 180

Population: The analysis population for this outcome includes the participants who achieved a rating of ≥ 2-grade improvement from baseline in LCL severity at maximum smile at Day 30 according to investigator assessments using the Facial Wrinkle Scale (FWS). This corresponds to the responders for Outcome 2. Note: Analyses of the secondary efficacy variables were performed using observed data.

The investigator evaluates the participant's LCL severity using a 4-grade scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3 = severe using the Facial Wrinkle Scale (FWS). The outcome is measured as median time to loss of treatment effect (i.e., return to moderate or severe LCL severity at maximum smile using the FWS).

Outcome measures

Measure	Placebo n=3 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=57 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
The Duration of Lateral Canthal Lines (LCL) Treatment in Participants Who Achieved a Rating of ≥ 2 Grade Improvement From Baseline in LCL Severity at Maximum Smile at Day 30 According to Investigator Assessments Using the Facial Wrinkle Scale (FWS)	242 Days The median duration and its 95% CI for placebo group was not meaningful as there were only 3 responders and therefore insufficient number of participants with events.	148 Days Interval 114.0 to 158.0

SECONDARY outcome

Timeframe: Day 60

Population: All secondary efficacy analyses endpoints were carried out using the Intent-To-Treat (ITT) analysis subset at day 60, which was defined as all participants who were randomized. Analyses of the secondary efficacy variables were performed using observed data.

The Satisfaction Question 5 grades facial line treatment satisfaction on a 5-point scale (-2 to 2) where -2=Very dissatisfied and 2=Very satisfied.

Outcome measures

Measure	Placebo n=67 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=137 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
The Percentage of Participants Reporting Mostly Satisfied/Very Satisfied on the Facial Line Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 for Lateral Canthal Lines (LCL)	4 Participants	107 Participants

SECONDARY outcome

Timeframe: Day 30

Population: This secondary efficacy analysis was carried out using the Intent-To-Treat (ITT) analysis subset at day 30, which was defined as all participants who were randomized. Analyses of the secondary efficacy variables were performed using observed data.

The investigator evaluates the participant's LCL severity using a 4-point scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3=severe.

The outcome was measured among participants who were at least mild at rest at baseline, where a responder was defined as achieving a >=1-grade improvement from baseline at Day 30.

Outcome measures

Measure	Placebo n=71 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=135 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
The Percentage of Responders for Investigator Assessments of Lateral Canthal Lines (LCL) Severity at Rest Using the Facial Wrinkle Scale (FWS)	11 Participants	75 Participants

SECONDARY outcome

Timeframe: AEs that started or worsen after the first dose of study intervention and up to 30 days after their last visit or study exit (Day 360 or early exit)

Population: All safety analyses were carried out using the Safety population set defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. Please note: Participants in placebo group who entered open-label phase (post Day 180) and received study intervention (MT10109L) are counted in MT10109L group. Thus, overall number of participants in MT10109L group is greater than what is noted in participants flow.

This section focuses primarily on Treatment Emergent Adverse Events(TEAEs), i.e., AEs that started or worsened after the first dose of study intervention (Day 1) until up to 30 days after their last visit or study exit. TEAE's are recorded by the PI and their study team from observations made after treatment administration. The safety analyses were conducted in the Safety population. Unless otherwise noted, safety results refer to TEAEs. All safety analyses were performed with participants analyzed by their actual treatment or regimen received.

Outcome measures

Measure	Placebo n=76 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=223 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Number of Patients Who Experienced an Adverse Event (AE) Through the Study Duration	12 Participants	78 Participants

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is the mean change in Systolic BP from baseline to study exit.

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=134 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Systolic Blood Pressure (BP)	1.8 mmHg Standard Deviation 12.28	0.5 mmHg Standard Deviation 11.83

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is the mean change in Diastolic BP from baseline to study exit.

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=134 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Diastolic Blood Pressure (BP)	0.4 mmHg Standard Deviation 9.73	0.3 mmHg Standard Deviation 9.42

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is the mean change in Pulse Rate from baseline to study exit.

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=134 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Pulse Rate	-2.0 beats/min Standard Deviation 13.13	-0.8 beats/min Standard Deviation 11.38

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is the mean change in Respiratory Rate from baseline to study exit.

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=134 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Respiratory Rate	0.7 breaths/min Standard Deviation 2.34	-0.1 breaths/min Standard Deviation 1.89

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in mean heart rate from baseline to studyexit

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=126 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Electrocardiogram (ECG) Parameters - Heart Rate	2.9 beats/min Standard Deviation 10.15	4.9 beats/min Standard Deviation 10.36

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in PR Interval from baseline to study exit

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=126 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Electrocardiogram (ECG) Parameters - PR Interval	-2.1 milliseconds Standard Deviation 12.76	-0.7 milliseconds Standard Deviation 13.65

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in QRS duration from baseline to study exit

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=126 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QRS Duration	2.6 milliseconds Standard Deviation 9.17	0.8 milliseconds Standard Deviation 7.14

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in QT Interval from baseline to study exit

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=126 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QT Interval	-3.9 milliseconds Standard Deviation 22.08	-11.3 milliseconds Standard Deviation 23.92

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in QTcB Interval from baseline to study exit

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=126 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcB Interval	3.7 milliseconds Standard Deviation 18.42	1.8 milliseconds Standard Deviation 20.3

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in QTcF Interval from baseline to study exit

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=126 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcF Interval	1.0 milliseconds Standard Deviation 14.97	-2.9 milliseconds Standard Deviation 16.79

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in RR Interval from baseline to study exit

Outcome measures

Measure	Placebo n=66 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=126 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Mean Change From Baseline in Electrocardiogram (ECG) Parameters - RR Interval	-32.2 milliseconds Standard Deviation 122.66	-58.2 milliseconds Standard Deviation 127.37

SECONDARY outcome

Timeframe: Baseline to Day 360

Population: The immunogenicity was analyzed in Safety population, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received.

Only samples that tested positive in the binding antibody confirmatory assay were evaluated for neutralizing antibodies. The participants with positive neutralizing antibodies are only shown.

Outcome measures

Measure	Placebo n=76 Participants Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=158 Participants MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
Number of Participants With Binding and Neutralizing Antibodies	0 Participants	2 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

MT10109L

Serious events: 7 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=76 participants at risk Placebo was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. Placebo: Placebo was injected into the LCL. In the open-label part, participants who met retreatment criteria were allowed up to 2 MT10109L	MT10109L n=223 participants at risk MT10109L was injected into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. MT10109L: MT10109L was injected into the LCL.
General disorders Death	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Infections and infestations COVID-19	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Infections and infestations Pneumonia	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Infections and infestations Suspected COVID-19	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Musculoskeletal and connective tissue disorders Exostosis	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/76 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.	0.45% 1/223 • Number of events 1 • The time frame for the treatment-emergent adverse events(TEAEs) was from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit) All safety analyses were carried out using the Safety population, defined as participants who received at least 1dose of study intervention. Participants were grouped based on their actual treatment received and not planned treatment. TEAE's experienced by the participants in the placebo group during the open-label part (MT10109L Cycles 2 and 3) were counted in MT10109L group.

Other adverse events

Adverse event data not reported

Additional Information

Young Ryu

Medytox Inc.

Phone: +82-2-6901-5424

Email: aab005@medytox.com

Results disclosure agreements

• Principal investigator is a sponsor employee General research agreement between the sponsor and PI's that includes a confidentiality section with a statement that the sponsor is and shall remain the exclusive owner of 'Information'. 'Information' shall include, but shall not be limited to, protocols, trade secrets, know-how, formulations, inventions, techniques, equipment, data and results.
• Publication restrictions are in place

Restriction type: OTHER