Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids (NCT NCT03601052)

Last Updated: 2021-08-18

Results Overview

The percentage of subjects with confirmed keloid formation at treated versus untreated lesions at 24 weeks (± 7 days) after first dose, analyzed using the modified Vancouver Scar Scale which reports a cumulative score based on subscores for vascularity, pliability and height.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

24 weeks (± 7 days) from first dose

Results posted on

2021-08-18

Participant Flow

Participants were recruited based on physician referral at four medical centers

Participant milestones

Participant milestones
Measure	Remlarsen-Treated Excisional Skin Wound and Placebo-Treated Excisional Skin Wound Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Overall Study STARTED	14
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Remlarsen-Treated Excisional Skin Wound and Placebo-Treated Excisional Skin Wound Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Overall Study Lost to Follow-up	2

Baseline Characteristics

Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Remlarsen-Treated Excisional Skin Wound and Placebo-Treated Excisional Skin Wound n=14 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants
Number of pre-existing keloids at screening	10.7 millimeters STANDARD_DEVIATION 5.44 • n=5 Participants
Height of largest pre-existing keloid	2.96 millimeters STANDARD_DEVIATION 3.96 • n=5 Participants
Width of largest pre-existing keloid	26.0 millimeters STANDARD_DEVIATION 35.0 • n=5 Participants
Length of largest pre-existing keloid	89.9 millimeters STANDARD_DEVIATION 83.6 • n=5 Participants
Volume of largest pre-existing keloid	10,366 millimeters cubed STANDARD_DEVIATION 22,607 • n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks (± 7 days) from first dose

Population: All subjects for whom an assessment of keloid formation using the modified Vancouver Scar Scale was performed at 24 weeks (± 7 days). Subjects who did not have keloid assessments within this time window were not included in the analysis.

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=14 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound n=14 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 24 Weeks	92.9 percentage of participants Interval 66.13 to 99.82	85.7 percentage of participants Interval 57.19 to 98.22

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks (± 7 days) from first dose

Population: Subjects for whom an analysis of improvement, defined as no confirmed keloid formation in the treated lesion vs. confirmed keloid formation in the untreated lesion based on assessment using the modified Vancouver Scar Scale, was performed at 24 weeks (± 7 days). Subjects who did not have an analysis of improvement, as defined, were not included in this outcome measure.

Percentage of subjects with improvement at 24 weeks (± 7 days), defined as no confirmed keloid formation in the treated lesion vs. confirmed keloid formation in the untreated lesion, based on assessment using the modified Vancouver Scar Scale which reports a cumulative score based on subscores for vascularity, pliability and height.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 weeks (± 7 days) from first dose

Population: All subjects for whom an assessment of keloid formation using the modified Vancouver Scar Scale was performed at 52 weeks (± 7 days). Subjects who did not have keloid assessments within this time window were not included in the analysis.

The percentage of subjects with confirmed keloid formation at treated versus untreated lesions at 52 weeks (± 7 days) after first dose, analyzed using the modified Vancouver Scar Scale which reports a cumulative score based on subscores for vascularity, pliability and height.

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=6 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound n=6 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 52 Weeks	100 percentage of participants Interval 54.07 to 100.0	66.7 percentage of participants Interval 22.28 to 95.67

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose to 365 days

Time to first confirmed keloid formation

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=14 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound n=14 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Time to Keloid Formation	58 days Interval 29.0 to 85.0	55 days Interval 22.0 to 71.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks from first dose

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=7 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound n=7 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Volume of Keloid at 24 Weeks	65 millimeters cubed Standard Deviation 58	79 millimeters cubed Standard Deviation 55

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 weeks from first dose

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=4 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound n=4 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Volume of Keloid at 52 Weeks	194 millimeters cubed Standard Deviation 142	156 millimeters cubed Standard Deviation 176

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose to 24 hours post-dose

Area under the curve (AUClast) for remlarsen + active metabolites (total active drug) after a single dose

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=14 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Single Dose	461 ng*hr/mL Standard Deviation 359	—

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose to 24 hours post-dose

Peak plasma concentration (Cmax) of remlarsen + active metabolites (total active drug) after first dose

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=14 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Peak Plasma Concentration (Cmax) of Remlarsen - Single Dose	29.3 ng/mL Standard Deviation 20.6	—

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose to up to 13 days post-dose

Area under the curve (AUClast) for remlarsen + active metabolites (total active drug) after multiple doses

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=12 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Multi-dose	1200 ng*hr/mL Standard Deviation 383	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Dosing on Day 10 or Day 12 through 24 hours post-dose

Peak plasma concentration (Cmax) of remlarsen + active metabolites (total active drug) after multiple doses

Outcome measures

Outcome measures
Measure	Remlarsen-Treated Excisional Skin Wound n=12 Participants Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.	Placebo-Treated Excisional Skin Wound Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject served as their own simultaneous control.
Peak Plasma Concentration (Cmax) of Remlarsen - Multi-dose	75.5 ng/mL Standard Deviation 23.7	—

Adverse Events

Treatment-emergent Adverse Events, Excluding Wound or Injection-site Related Events

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Wound or Injection Site-related Treatment-emergent Adverse Events

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Regulatory Affairs

Viridian Therapeutics (formerly miRagen Therapeutics)

Phone: 720-722-5917

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigators in this study may present or publish study results in scientific journals or other scholarly media without prior written approval after the following conditions have been met: * Results of study have been publicly disclosed by or with the consent of the sponsor * Investigator has complied with the Clinical Trial Agreement and requests from the sponsor to delete confidential information (other than study results) * Study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Treatment-emergent Adverse Events, Excluding Wound or Injection-site Related Events n=14 participants at risk All subjects; all treatment-emergent adverse events, excluding wound or injection site-related events	Wound or Injection Site-related Treatment-emergent Adverse Events n=14 participants at risk All subjects; wound or injection site-related treatment-emergent adverse events
Injury, poisoning and procedural complications Procedural pain	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	35.7% 5/14 • Number of events 6 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Injection site oedema	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Injection site erythema	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Injury, poisoning and procedural complications Incision site pruritus	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	35.7% 5/14 • Number of events 6 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Injection site pain	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Injection site reaction	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Abdominal pain lower	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Constipation	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Diarrhoea	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Nausea	14.3% 2/14 • Number of events 3 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Toothache	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Renal and urinary disorders Urine odour abnormal	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Skin and subcutaneous tissue disorders Pruritus	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Skin and subcutaneous tissue disorders Blister	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Skin and subcutaneous tissue disorders Urticaria	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Musculoskeletal and connective tissue disorders Back pain	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Investigations Red blood cell count decreased	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Investigations Blood creatine phosphokinase increased	7.1% 1/14 • Number of events 2 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Investigations Blood lactate dehydrogenase increased	28.6% 4/14 • Number of events 11 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Investigations Monocyte count increased	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Investigations Neutrophil count increased	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Investigations White blood cell count increased	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Nervous system disorders Dizziness	14.3% 2/14 • Number of events 2 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Nervous system disorders Headache	7.1% 1/14 • Number of events 2 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Injury, poisoning and procedural complications Arthropod bite	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Injury, poisoning and procedural complications Muscle strain	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Injury, poisoning and procedural complications Wound haematoma	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Eye disorders Visual impairment	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Metabolism and nutrition disorders Hypercholesterolemia	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Metabolism and nutrition disorders Glucose tolerance impaired	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Metabolism and nutrition disorders Vitamin D deficiency	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Fungal infection	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Influenza	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Urinary tract infection	14.3% 2/14 • Number of events 3 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Groin infection	7.1% 1/14 • Number of events 1 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/14 • All adverse events from clinical trial initiation until 30 days post-dose regardless of relationship, and Related events until the end of the protocol-specified observation period. Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.