Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of AVTX-002 for the Treatment of Poorly Controlled Non-Eosinophilic Asthma. (NCT NCT05288504)

Last Updated: 2024-09-05

Results Overview

Percentage of patients who experience any of the following asthma related events: * ≥6 additional reliever puffs of Short-Acting Beta-Agonist (compared to baseline) in a 24-hour period on 2 consecutive days or, * increase in inhaled corticosteroid dose ≥4 times than the dose at baseline or, * a decrease in peak flow of 30% or more (compared to baseline) on 2 consecutive days of treatment, or * an asthma exacerbation requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days, or * a hospitalization or emergency room visit because of an asthma exacerbation

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

91 participants

Primary outcome timeframe

Through Week 14

Results posted on

2024-09-05

Participant Flow

Participant milestones

Participant milestones
Measure	AVTX-002 AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Overall Study STARTED	45	46
Overall Study Safety Analysis Set	45	45
Overall Study Full Analysis Set	45	45
Overall Study Per Protocol Analysis Set	43	41
Overall Study PK Analysis Set	45	0
Overall Study COMPLETED	36	32
Overall Study NOT COMPLETED	9	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of AVTX-002 for the Treatment of Poorly Controlled Non-Eosinophilic Asthma.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AVTX-002 n=45 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=46 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.	Total n=91 Participants Total of all reporting groups
Age, Continuous	45.5 years STANDARD_DEVIATION 14.60 • n=5 Participants	47.6 years STANDARD_DEVIATION 15.99 • n=7 Participants	46.6 years STANDARD_DEVIATION 15.27 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	32 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	14 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	34 Participants n=7 Participants	65 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	17 Participants n=5 Participants	10 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	35 Participants n=7 Participants	63 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	45 participants n=5 Participants	46 participants n=7 Participants	91 participants n=5 Participants
Weight	95.60 kg STANDARD_DEVIATION 23.661 • n=5 Participants	87.94 kg STANDARD_DEVIATION 21.343 • n=7 Participants	91.73 kg STANDARD_DEVIATION 22.722 • n=5 Participants
Height	168.41 cm STANDARD_DEVIATION 9.900 • n=5 Participants	167.69 cm STANDARD_DEVIATION 10.865 • n=7 Participants	168.04 cm STANDARD_DEVIATION 10.347 • n=5 Participants
BMI	33.95 kg/m^2 STANDARD_DEVIATION 8.917 • n=5 Participants	31.20 kg/m^2 STANDARD_DEVIATION 6.329 • n=7 Participants	32.56 kg/m^2 STANDARD_DEVIATION 7.798 • n=5 Participants
Screening eosinophil level < 150 eosinophils per micro liter	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
Screening eosinophil level >= 150 eosinophils per micro liter	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants

PRIMARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	AVTX-002 n=45 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=45 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
The Ability of AVTX-002 to Improve Asthma Control in Subjects With Poorly Controlled Non-eosinophilic Asthma (NEA) Based on the Percentage of Patients Who Experience Asthma Related Events.	12 Participants	14 Participants

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

The FEV1 is the volume of air that can be forcibly exhaled from the lungs in the first second, measured in liters by a spirometer.

Outcome measures

Outcome measures
Measure	AVTX-002 n=42 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=42 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in Forced Expiratory Volume in 1 Second (FEV1[Liters]).	-0.149 Liter Standard Deviation 0.309	-0.203 Liter Standard Deviation 0.405

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set

Time to event will be measured in days using the first day of the event to denote the day of the overall asthma related event occurrence.

Outcome measures

Outcome measures
Measure	AVTX-002 n=45 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=45 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Time to Asthma Exacerbation. Time to first asthma related event or time to censoring	84.9 days Standard Deviation 28.03	78.1 days Standard Deviation 30.58
Time to Asthma Exacerbation. Time to first asthma related event - Subjects with an asthma related event	52.1 days Standard Deviation 31.83	42.6 days Standard Deviation 26.69

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

A FeNO test measures the levels of nitric oxide during exhalation. A FeNO test will be done by breathing into a tube attached to a hand-held monitor.

Outcome measures

Outcome measures
Measure	AVTX-002 n=42 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=42 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in Fractional Exhaled Nitric Oxide (FeNO).	6.1 Parts per billion Standard Deviation 15.54	3.8 Parts per billion Standard Deviation 27.64

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

This is a simple questionnaire to measure the adequacy of asthma control and change in asthma control. ACQ has a multidimensional construct assessing symptoms (5 items, self-administered), rescue bronchodilator use (1 item, self-administered), and FEV1 (1 item, completed by study staff). Scores range between 0 (totally controlled) and 6 (severely uncontrolled).

Outcome measures

Outcome measures
Measure	AVTX-002 n=42 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=42 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in Asthma Control Questionnaire (ACQ).	-0.22 score on a scale Standard Deviation 1.077	-0.34 score on a scale Standard Deviation 0.999

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

The AQLQ(S)+12 is a modified version of the standardized AQLQ and includes 32 questions in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). Subjects will be asked to recall their experiences during the previous 2 weeks and score each of the questions on a 7-point scale, where 7=not at all limited and 1=totally limited. The overall score of the AQLQ +12 will be derived as the average of the 32 questions; thus, the total score ranges from 1 (indicates "total impairment") to 7 (indicates "no impairment").

Outcome measures

Outcome measures
Measure	AVTX-002 n=42 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=42 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12).	0.18 score on a scale Standard Deviation 1.423	0.49 score on a scale Standard Deviation 1.162

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

The Asthma Symptom Diary is a 6-item daily measure of asthma symptom severity that assesses three core categories of asthma symptoms: breathing symptoms (difficulty breathing; wheezing; shortness of breath), chest symptoms (chest tightness; chest pain), and cough. Subjects are required to rate the 6 symptoms at their worst each day using an 11-point numeric rating scale ranging from 0 ('None') to 10 ('As bad as you can imagine'). The Asthma Symptom Diary score is the sum of the 6 individual symptom scores (the range is from 0-60, where a higher score indicates more severe symptoms) reported as a weekly average.

Outcome measures

Outcome measures
Measure	AVTX-002 n=35 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=28 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in Asthma Symptom Diary Score.	-0.15 units on a scale Standard Deviation 1.469	-0.39 units on a scale Standard Deviation 1.318

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ VAS. The EQ VAS records the subject's self-rated health on a vertical VAS with a score of 0-100, where the endpoints are labelled 0 for 'The worst health you can imagine' and 100 for 'The best health you can imagine'.

Outcome measures

Outcome measures
Measure	AVTX-002 n=42 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=42 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in European Quality of Life - 5 Dimension 5 Level Questionnaire in Visual Analogue Scale Score (EQ VAS).	2.9 units on a scale Standard Deviation 22.60	5.6 units on a scale Standard Deviation 15.28

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

The Patient Global Impression of Change (PGI-C) is a single question scale asking the patient to rate the overall status of their specific condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The Patient Global Impression of Severity (PGI-S) is a single question scale asking the patient to rate current state of their specific condition on a 7-point scale ranging from 1 (normal) to 7 (extreme).

Outcome measures

Outcome measures
Measure	AVTX-002 n=42 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=42 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in Patient Global Impression of Change/Severity. PGI-S	0.0 units on a scale Standard Deviation 1.28	-0.4 units on a scale Standard Deviation 1.31
Change From Baseline to Week 14 in Patient Global Impression of Change/Severity. PGI-C	3.4 units on a scale Standard Deviation 1.50	3.0 units on a scale Standard Deviation 1.63

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

The Clinician Global Impression of Improvement (CGI-I) is a single question scale asking clinician to rate the overall status of the patient's specific condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The Clinician Global Impression of Severity (CGI-S) is a single question scale asking the clinician to rate current state of the patient's specific condition on a 7-point scale ranging from 1 (normal) to 7 (extreme).

Outcome measures

Outcome measures
Measure	AVTX-002 n=42 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=42 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in Clinician Global Impression of Improvement/Severity. CGI-S	-0.3 units on a scale Standard Deviation 0.86	-0.5 units on a scale Standard Deviation 1.33
Change From Baseline to Week 14 in Clinician Global Impression of Improvement/Severity. CGI-I	3.4 units on a scale Standard Deviation 1.32	3.2 units on a scale Standard Deviation 1.52

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

The number of times a short-acting beta agonist (number of inhalations) was used was assessed daily and reported as a weekly average.

Outcome measures

Outcome measures
Measure	AVTX-002 n=37 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=32 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
The Number of Inhalations of Short-acting Beta Agonist (SABA) at Week 14.	1.28 number of inhalations Standard Deviation 1.507	0.97 number of inhalations Standard Deviation 1.695

SECONDARY outcome

Timeframe: Through Week 14

Population: Full Analysis Set with all subjects with baseline and Week 14 data available.

Change from baseline in serum soluble LIGHT levels.

Outcome measures

Outcome measures
Measure	AVTX-002 n=42 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=41 Participants Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Change From Baseline to Week 14 in Serum Soluble LIGHT Levels (Lymphotoxin-like, Exhibits Inducible Expression, and Competes With Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a Receptor Expressed by T Lymphocytes).	-114.52 pg/mL Standard Deviation 80.781	11.63 pg/mL Standard Deviation 92.147

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12 and Week 14.

Population: Safety Analysis Set: Data only collected for "AVTX-002" Arm/Group.

Incidence of anti-drug antibodies (ADAs) at Baseline, Week 2, Week 4, Week 6, Week 8, Week 12 and Week 14.

Outcome measures

Outcome measures
Measure	AVTX-002 n=45 Participants AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. Baseline	0 Participants	—
Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. Week 2	1 Participants	—
Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. Week 4	0 Participants	—
Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. Week 6	0 Participants	—
Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. Week 8	0 Participants	—
Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. Week 12	0 Participants	—
Incidence of Anti-drug Antibodies (ADAs) at Each Timepoint. Week 14	0 Participants	—

Adverse Events

AVTX-002

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Garry Neil, MD

Avalo Therapeutics, Inc.

Phone: 610.254.4201

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	AVTX-002 n=45 participants at risk AVTX-002: Dose of 600 mg administered subcutaneously three times during the study.	Placebo n=45 participants at risk Placebo: Placebo sourced as normal saline administered subcutaneously three times during the study.
Gastrointestinal disorders Diarrhoea	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Gastrointestinal disorders Food poisoning	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Gastrointestinal disorders Oesophageal obstruction	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Gastrointestinal disorders Abdominal pain	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Gastrointestinal disorders Toothache	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
General disorders Injection site pain	4.4% 2/45 • Number of events 2 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
General disorders Fatigue	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations COVID-19	4.4% 2/45 • Number of events 2 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	4.4% 2/45 • Number of events 2 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Nasopharyngitis	4.4% 2/45 • Number of events 2 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Upper respiratory tract infection	4.4% 2/45 • Number of events 2 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	4.4% 2/45 • Number of events 2 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Bronchitis bacterial	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Influenza	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Bronchitis	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Gastroenteritis	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Gastroenteritis viral	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Gastrointestinal viral infection	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Infections and infestations Oral herpes	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Injury, poisoning and procedural complications Skin laceration	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Investigations Blood cholesterol increased	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Investigations Blood urine present	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Investigations White blood cell count increased	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Investigations Blood creatine phosphokinase increased	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	4.4% 2/45 • Number of events 2 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Investigations Blood potassium decreased	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 3/45 • Number of events 3 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Musculoskeletal and connective tissue disorders Myalgia	6.7% 3/45 • Number of events 3 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Nervous system disorders Headache	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/45 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.	2.2% 1/45 • Number of events 1 • Treatment emergent AEs were collected from the time of first dose through week 14 (14 weeks total). An AE will be considered treatment emergent if it occurs on or after the time (or date, if time not recorded) of first dose of IP and within 28 days after a subject's last dose of IP.