Trial Outcomes & Findings for Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis (NCT NCT02370693)

Last Updated: 2021-08-25

Results Overview

To assess the safety and tolerability of bortezomib with mycophenolate mofetil assessed by the incidence of serious adverse events.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

First dosing day to last study visit day: Mean duration 8 months.

Results posted on

2021-08-25

Participant Flow

2 subjects were enrolled (signed consent form) but did not continue through the screening process far enough to reach randomization.

Participant milestones

Participant milestones
Measure	Bortezomib Plus Mycophenolate Mofetil Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks	Placebo Plus Mycophenolate Mofetil Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks
Overall Study STARTED	3	4
Overall Study COMPLETED	2	3
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bortezomib Plus Mycophenolate Mofetil n=3 Participants Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks	Placebo Plus Mycophenolate Mofetil n=4 Participants Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks	Enrolled But Not Randomized n=2 Participants Subjects who were enrolled (signed consent form) but did not continue through the screening process far enough to reach randomization.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=99 Participants	4 Participants n=107 Participants	2 Participants n=206 Participants	8 Participants n=7 Participants
Age, Categorical >=65 years	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Age, Continuous	59.4 years STANDARD_DEVIATION 8.1 • n=99 Participants	52.3 years STANDARD_DEVIATION 4.6 • n=107 Participants	42.6 years STANDARD_DEVIATION 10.4 • n=206 Participants	52.6 years STANDARD_DEVIATION 8.9 • n=7 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	2 Participants n=107 Participants	0 Participants n=206 Participants	4 Participants n=7 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	5 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) White	3 Participants n=99 Participants	3 Participants n=107 Participants	2 Participants n=206 Participants	8 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Region of Enrollment United States	3 participants n=99 Participants	4 participants n=107 Participants	2 participants n=206 Participants	9 participants n=7 Participants

PRIMARY outcome

Timeframe: First dosing day to last study visit day: Mean duration 8 months.

Population: All subjects who received at least one dose.

To assess the safety and tolerability of bortezomib with mycophenolate mofetil assessed by the incidence of serious adverse events.

Outcome measures

Outcome measures
Measure	Bortezomib Plus Mycophenolate Mofetil n=3 Participants Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks	Placebo Plus Mycophenolate Mofetil n=4 Participants Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks
Number of Participants With Serious Adverse Events	0.33 Number of Participants with Serious Adve Standard Deviation .58	0.25 Number of Participants with Serious Adve Standard Deviation .50

SECONDARY outcome

Timeframe: 24 weeks

Population: All subjects who had comparable skin score data.

The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness that sums individual scores of skin thickness (0 - No Thickening, 1 - Mild Thickening, 2 - Moderate Thickening, 3 - Severe Thickening) measured at 17 body sites to reach a total score (Range: 0 to 51, higher value representing thicker skin). The Score is used as a surrogate for disease activity and severity, and a worsening score over time is associated with worse outcomes.

Outcome measures

Outcome measures
Measure	Bortezomib Plus Mycophenolate Mofetil n=3 Participants Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks	Placebo Plus Mycophenolate Mofetil n=3 Participants Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks
Change of Skin Fibrosis Measured by the Rodnan Skin Score Between Baseline and 24 Weeks	-3.00 Score on a Scale Standard Deviation 2.65	-0.33 Score on a Scale Standard Deviation 0.58

SECONDARY outcome

Timeframe: 24 weeks

Population: All subjects who had comparable forced vital capacity data.

Forced vital capacity, or FVC, is the amount in liters of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It measures the effect that lung disease has on a person's ability to inhale and exhale. Higher values are better, and decreases over time can indicate disease progression.

Outcome measures

Outcome measures
Measure	Bortezomib Plus Mycophenolate Mofetil n=3 Participants Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks	Placebo Plus Mycophenolate Mofetil n=3 Participants Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks
Change of Lung Function Measured by Forced Vital Capacity (FVC) Between Baseline and 24 Weeks	0.51 Percentage of change in FVC %predicted Standard Deviation 0.55	-0.69 Percentage of change in FVC %predicted Standard Deviation 1.02

Adverse Events

Bortezomib Plus Mycophenolate Mofetil

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo Plus Mycophenolate Mofetil

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bortezomib Plus Mycophenolate Mofetil n=3 participants at risk Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks	Placebo Plus Mycophenolate Mofetil n=4 participants at risk Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks
Infections and infestations Herpes Zoster Infection	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Infections and infestations Respiratory Syncytial Virus Bilaterial Pneumonia	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.

Other adverse events

Additional Information

Manu Jain, MD

Northwestern University

Phone: 312-503-4242

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Bortezomib Plus Mycophenolate Mofetil n=3 participants at risk Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Bortezomib: Bortezomib 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks	Placebo Plus Mycophenolate Mofetil n=4 participants at risk Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month and mycophenolate mofetil 1.5 g orally twice daily for 24 weeks Placebo: Placebo (normal saline) 1.3 mg/m² subcutaneously (or IV push if unable to tolerate subcutaneous injection) once per week for the first two weeks per month for 24 weeks Mycophenolate mofetil: Mycophenolate mofetil 1.5 g twice a day orally for 24 weeks
Musculoskeletal and connective tissue disorders Left ankle pain	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Nasal congestion	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Metabolism and nutrition disorders High cholesterol	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Ache on forehead and eyelids	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Gastrointestinal disorders Acid reflux	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Musculoskeletal and connective tissue disorders Bach ache	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Gastrointestinal disorders Bloating	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Musculoskeletal and connective tissue disorders Body aches	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Injury, poisoning and procedural complications Bruising at injection site	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Injury, poisoning and procedural complications Burning sensation at injection site	33.3% 1/3 • Number of events 2 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Chills	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Infections and infestations Cold	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Cold sweats	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Cough with increased mucus	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Gastrointestinal disorders Diarrhea	66.7% 2/3 • Number of events 5 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Dry cough	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 2 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Eye disorders Dry eyes	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Skin and subcutaneous tissue disorders Dry Skin	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Dry throat	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Fatigue	66.7% 2/3 • Number of events 3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Gastrointestinal disorders Gastroparesis	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Headache	100.0% 3/3 • Number of events 9 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 2 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Gastrointestinal disorders Nausea	66.7% 2/3 • Number of events 14 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Injury, poisoning and procedural complications Pain at injection site	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Musculoskeletal and connective tissue disorders Pain in right shoulder	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Endocrine disorders Pre-diabetes	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Productive cough	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Prolonged coughing episode	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Injury, poisoning and procedural complications Redness at injection site	100.0% 3/3 • Number of events 6 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Musculoskeletal and connective tissue disorders Right side back muscle spasm	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Runny nose	33.3% 1/3 • Number of events 3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Shaking	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Injury, poisoning and procedural complications Skin peeling at injection site	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Injury, poisoning and procedural complications Tingling at injection site	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Sore throat	33.3% 1/3 • Number of events 2 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Injury, poisoning and procedural complications Soreness at injection site	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Nervous system disorders Tingling sensation on face	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Surgical and medical procedures Tooth extraction	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Gastrointestinal disorders Upset stomach	33.3% 1/3 • Number of events 2 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Renal and urinary disorders Urinary tract infection	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	50.0% 2/4 • Number of events 2 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Gastrointestinal disorders Vomiting due to coughing	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Injury, poisoning and procedural complications Warmth at injection site	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Weight loss of ~10 lbs	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Worsened body aches	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Worsened cough	33.3% 1/3 • Number of events 3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
General disorders Worsened fatigue	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Gastrointestinal disorders Worsening diarrhea	33.3% 1/3 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	0.00% 0/4 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.
Respiratory, thoracic and mediastinal disorders Worsening shortness of breath	0.00% 0/3 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.	25.0% 1/4 • Number of events 1 • First dosing day to last study visit day: Mean duration 8 months. Adverse event information collected by study team at each study visit.