Trial Outcomes & Findings for Phase II Study of Adenovirus/PSA Vaccine in Men With Recurrent Prostate Cancer After Local Therapy APP21 (NCT NCT00583752)

Last Updated: 2023-05-18

Results Overview

Anti-immunologic response is defined as an increase of \>200% above pre-immunization levels of anti-PSA T cells as measured by ELISPOT analysis

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

18 months

Results posted on

2023-05-18

Participant Flow

Participant milestones

Participant milestones
Measure	Androgen Deprivation Therapy (ADT) + Adenovirus/PSA Vaccine On Arm B, subjects will be started on androgen deprivation therapy (ADT) 14 days prior to beginning the vaccinations. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60	Adenovirus/PSA Vaccine On Arm A, subjects can begin the three vaccinations immediately. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60
Overall Study STARTED	25	25
Overall Study COMPLETED	20	20
Overall Study NOT COMPLETED	5	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Androgen Deprivation Therapy (ADT) + Adenovirus/PSA Vaccine On Arm B, subjects will be started on androgen deprivation therapy (ADT) 14 days prior to beginning the vaccinations. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60	Adenovirus/PSA Vaccine On Arm A, subjects can begin the three vaccinations immediately. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60
Overall Study Lost to Follow-up	5	5

Baseline Characteristics

Phase II Study of Adenovirus/PSA Vaccine in Men With Recurrent Prostate Cancer After Local Therapy APP21

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Androgen Deprivation Therapy (ADT) + Adenovirus/PSA Vaccine n=25 Participants On Arm B, subjects will be started on androgen deprivation therapy (ADT) 14 days prior to beginning the vaccinations. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60	Adenovirus/PSA Vaccine n=25 Participants On Arm A, subjects can begin the three vaccinations immediately. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60	Total n=50 Participants Total of all reporting groups
Age, Continuous	71 years n=5 Participants	69 years n=7 Participants	70 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	24 Participants n=7 Participants	49 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	23 Participants n=7 Participants	48 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	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: 21 evaluable participants analyzed on Arm A and included in analysis of outcome measure one. 1 participant was lost to long-term follow-up for outcome measure three.

Anti-immunologic response is defined as an increase of \>200% above pre-immunization levels of anti-PSA T cells as measured by ELISPOT analysis

Outcome measures

Outcome measures
Measure	Androgen Deprivation Therapy (ADT) + Adenovirus/PSA Vaccin n=20 Participants On Arm B, subjects will be started on androgen deprivation therapy (ADT) 14 days prior to beginning the vaccinations. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60	Adenovirus/PSA Vaccine n=21 Participants On Arm A, subjects can begin the three vaccinations immediately. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60
Number of Participants Who Develop a Strong or Modest Anti-PSA Immune Response Stong response	12 participants	14 participants
Number of Participants Who Develop a Strong or Modest Anti-PSA Immune Response Modest response	6 participants	3 participants

SECONDARY outcome

Timeframe: 18 months

Population: PSA levels and doubling times could not be analyzed for participants in Arm B due to the fact that their ADT reduces serum PSA.

To evaluate the increase, decrease, or stable response rates (PSA responses and changes in PSADT) of the Ad/PSA vaccine using a prime-boost immunization strategy. PSADT will be calculated based on the MSKCC online calculator.

Outcome measures

Outcome measures
Measure	Androgen Deprivation Therapy (ADT) + Adenovirus/PSA Vaccin On Arm B, subjects will be started on androgen deprivation therapy (ADT) 14 days prior to beginning the vaccinations. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60	Adenovirus/PSA Vaccine n=19 Participants On Arm A, subjects can begin the three vaccinations immediately. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60
Number of Participants With Stable, Decreased, or Increased PSA Doubling Times (PSADT) Decreased PSADT	—	4 participants
Number of Participants With Stable, Decreased, or Increased PSA Doubling Times (PSADT) Stable PSADT	—	2 participants
Number of Participants With Stable, Decreased, or Increased PSA Doubling Times (PSADT) Increased PSADT/PSA decline	—	13 participants

SECONDARY outcome

Timeframe: Every 6 months, up to 14 years

Population: 5 participants lost to follow-up in Arm A, 5 participants lost to follow-up in Arm B

To evaluate survival in evaluable patients receiving the Ad/PSA vaccine, as measured by 2-year, 5-year, 10-year, and overall survival (OS)

Outcome measures

Outcome measures
Measure	Androgen Deprivation Therapy (ADT) + Adenovirus/PSA Vaccin n=20 Participants On Arm B, subjects will be started on androgen deprivation therapy (ADT) 14 days prior to beginning the vaccinations. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60	Adenovirus/PSA Vaccine n=20 Participants On Arm A, subjects can begin the three vaccinations immediately. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60
Number of Participants Alive and Deceased Following Treatment Overall survival · Deceased	17 Participants	10 Participants
Number of Participants Alive and Deceased Following Treatment 2-year survival · Alive	20 Participants	20 Participants
Number of Participants Alive and Deceased Following Treatment 2-year survival · Deceased	0 Participants	0 Participants
Number of Participants Alive and Deceased Following Treatment 5-year survival · Alive	19 Participants	20 Participants
Number of Participants Alive and Deceased Following Treatment 5-year survival · Deceased	1 Participants	0 Participants
Number of Participants Alive and Deceased Following Treatment 10-year survival · Alive	14 Participants	11 Participants
Number of Participants Alive and Deceased Following Treatment 10-year survival · Deceased	6 Participants	9 Participants
Number of Participants Alive and Deceased Following Treatment Overall survival · Alive	3 Participants	10 Participants

Adverse Events

Androgen Deprivation Therapy (ADT) + Adenovirus/PSA Vaccine

Serious events: 0 serious events

Other events: 15 other events

Deaths: 17 deaths

Adenovirus/PSA Vaccin

Serious events: 0 serious events

Other events: 18 other events

Deaths: 10 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

David Lubaroff, MD

University of Iowa, Holden Comprehensive Cancer Center

Phone: 3193561527

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Androgen Deprivation Therapy (ADT) + Adenovirus/PSA Vaccine n=25 participants at risk On Arm B, subjects will be started on androgen deprivation therapy (ADT) 14 days prior to beginning the vaccinations. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60	Adenovirus/PSA Vaccin n=25 participants at risk On Arm A, subjects can begin the three vaccinations immediately. Adenovirus/PSA Vaccine: 1x10E8pfu in Gelfoam subcutaneously on day 0, 30, 60
Nervous system disorders Headache	8.0% 2/25 • Number of events 2 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	8.0% 2/25 • Number of events 2 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Gastrointestinal disorders Diarrhea	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	8.0% 2/25 • Number of events 2 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Gastrointestinal disorders Increase voiding frequency	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Vascular disorders Facial flushing	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Skin and subcutaneous tissue disorders Folliculitis	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Gastrointestinal disorders Mucositis	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Gastrointestinal disorders Pain, GI; oral cavity	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Investigations Injection site reaction	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	8.0% 2/25 • Number of events 2 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Renal and urinary disorders Urinary tract infection	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Infections and infestations Infection, bug bites on skin	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Respiratory, thoracic and mediastinal disorders Common cold	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	12.0% 3/25 • Number of events 3 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
General disorders Sleeplessness	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Metabolism and nutrition disorders Hypertension	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Eye disorders Uveitis	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Renal and urinary disorders Ketonuria	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Renal and urinary disorders Elevated leukocyte esterase	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Surgical and medical procedures Tooth pain/extraction	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Respiratory, thoracic and mediastinal disorders Sinus drainage	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
General disorders Dizziness	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Cardiac disorders Ventricular arrhythmia	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Respiratory, thoracic and mediastinal disorders Upper airway infection	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Skin and subcutaneous tissue disorders Drainage of cyst	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
General disorders Fatigue	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Reproductive system and breast disorders Decreased libido	8.0% 2/25 • Number of events 2 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
General disorders Hot flashes	44.0% 11/25 • Number of events 11 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Renal and urinary disorders Increased urinary frequency	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Renal and urinary disorders Increased urinary urgency	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Reproductive system and breast disorders Increased erectile dysfunction	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Musculoskeletal and connective tissue disorders Myositis	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Reproductive system and breast disorders Gynecomastia	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Cardiac disorders Cardiac pain	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Gastrointestinal disorders Epigastric pain	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
General disorders Flu	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Respiratory, thoracic and mediastinal disorders Shortness of breath	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Gastrointestinal disorders Stomach ache	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Investigations Elevated ALT	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Investigations Elevated AST	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Musculoskeletal and connective tissue disorders Leg cramp	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Skin and subcutaneous tissue disorders Basal cell cancer	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).
Nervous system disorders Cerebrovascular accident	4.0% 1/25 • Number of events 1 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).	0.00% 0/25 • All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).