Trial Outcomes & Findings for Extracorporeal Photopheresis (ECP) With Methoxsalen for Chronic Graft Versus Host Disease (cGVHD) (NCT NCT01380535)

Last Updated: 2020-02-19

Results Overview

Participants with overall response included those with partial response or complete response, according to study staff who did not know which treatment they received (blinded assessment).

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

60 participants

Primary outcome timeframe

Week 28

Results posted on

2020-02-19

Participant Flow

Patients were enrolled in Austria, France, Germany, Italy, Hungary, Spain, the United Kingdom, and the United States. Enrollment started in November 2011, and the last patient visit occurred in March 2015.

All participants enrolled were included in the safety analysis set

Participant milestones

Participant milestones
Measure	ECP Methoxsalen + SoC Participants receive ECP methoxsalen in addition to standard of care	Standard of Care (SoC) Participants receive only standard of care
Overall Study STARTED	29	31
Overall Study Baseline Population	29	31
Overall Study Safety Population	28	28
Overall Study Intent-to-treat Population	29	24
Overall Study COMPLETED	22	16
Overall Study NOT COMPLETED	7	15

Reasons for withdrawal

Reasons for withdrawal
Measure	ECP Methoxsalen + SoC Participants receive ECP methoxsalen in addition to standard of care	Standard of Care (SoC) Participants receive only standard of care
Overall Study Adverse Event	3	3
Overall Study Death	3	0
Overall Study Study site closed	0	5
Overall Study Withdrawal by Subject	1	2
Overall Study Protocol Violation	0	2
Overall Study Lack of Efficacy	0	3

Baseline Characteristics

Extracorporeal Photopheresis (ECP) With Methoxsalen for Chronic Graft Versus Host Disease (cGVHD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ECP Methoxsalen + SoC n=29 Participants Participants receive ECP methoxsalen in addition to standard of care	Standard of Care (SOC) n=31 Participants Participants receive only standard of care	Total n=60 Participants Total of all reporting groups
Age, Customized 18-44 years	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Age, Customized 45-64 years	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Age, Customized 65 years and over	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	13 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized White	22 Participants n=5 Participants	24 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Not Collected	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Austria	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Hungary	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Italy	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment France	4 participants n=5 Participants	6 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Germany	11 participants n=5 Participants	7 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Spain	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 28

Population: Intention to treat population

Participants with overall response included those with partial response or complete response, according to study staff who did not know which treatment they received (blinded assessment).

Outcome measures

Outcome measures
Measure	ECP Methoxsalen + SoC n=29 Participants Participants receive ECP methoxsalen in addition to standard of care	Standard of Care (SoC) n=24 Participants Participants receive only standard of care
Number of Participants With an Overall Response at Week 28	20 Participants	14 Participants

Adverse Events

ECP Methoxsalen + SoC

Serious events: 8 serious events

Other events: 26 other events

Deaths: 4 deaths

Standard of Care (SoC)

Serious events: 9 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information Call Center

Mallinckrodt Pharmaceuticals

Phone: 800-556-3314

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	ECP Methoxsalen + SoC n=28 participants at risk Participants receive ECP methoxsalen in addition to standard of care	Standard of Care (SoC) n=28 participants at risk Participants receive only standard of care
Cardiac disorders Cardiac Failure	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Endocrine disorders Thyroiditis subacute	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Immune system disorders Graft versus host disease in liver	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Bronchopulmonary aspergillosis	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Cytomegalovirus infection	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Escherichia infection	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Escherichia sepsis	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Herpes simplex	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Herpes zoster	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Lower respiratory tract infection	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Respiratory tract infection	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Respiratory tract infection viral	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Sepsis	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Sinusitis	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Toxoplasmosis	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Viraemia	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Dehydration	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Hyperglycaemia	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Hypokalaemia	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Musculoskeletal and connective tissue disorders Myopathy	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Nervous system disorders Polyneuropathy	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Psychiatric disorders Confusional state	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Psychiatric disorders Depression	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Renal and urinary disorders Renal failure acute	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Respiratory, thoracic and mediastinal disorders Vocal cord polyp	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.

Other adverse events
Measure	ECP Methoxsalen + SoC n=28 participants at risk Participants receive ECP methoxsalen in addition to standard of care	Standard of Care (SoC) n=28 participants at risk Participants receive only standard of care
Blood and lymphatic system disorders Anaemia	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Blood and lymphatic system disorders Thrombocytopenia	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Eye disorders Dry Eye	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Gastrointestinal disorders Abdominal Pain	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Gastrointestinal disorders Constipation	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Gastrointestinal disorders Diarrhoea	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
General disorders Asthenia	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
General disorders Fatigue	17.9% 5/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
General disorders Oedema peripheral	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
General disorders Pyrexia	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Epstein-Barr virus infection	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Infections and infestations Rhinitis	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Alanine aminotransferase increased	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Aspartate aminotransferase increased	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Blood alkaline phosphatase increased	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Blood cholesterol increased	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Blood creatinine increased	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Blood lactate dehydrogenase increased	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Blood pressure increased	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Blood urea increased	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Gamma-glutamyltransferase increased	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Investigations Platelet count decreased	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Hyperglycaemia	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Hypertriglyceridaemia	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Hypokalaemia	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Hypomagnesaemia	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Metabolism and nutrition disorders Hypoproteinaemia	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Musculoskeletal and connective tissue disorders Back pain	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	17.9% 5/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Musculoskeletal and connective tissue disorders Myopathy	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	0.00% 0/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Musculoskeletal and connective tissue disorders Pain in extremity	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Psychiatric disorders Insomnia	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	10.7% 3/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Psychiatric disorders Sleep disorder	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Respiratory, thoracic and mediastinal disorders Cough	21.4% 6/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Skin and subcutaneous tissue disorders Dry Skin	3.6% 1/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Vascular disorders Hypertension	32.1% 9/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.9% 5/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Nervous system disorders Paraesthesia	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.
Nervous system disorders Dizziness	14.3% 4/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.	7.1% 2/28 • Treatment emergent adverse events were recorded from the start of treatment through Week 28. Treatment emergent adverse events (TEAEs) are unpleasant events not there before the medical treatment, or that were there, but got worse or happened more often after the treatment. Both serious and non-serious adverse events reported here are TEAEs. All-cause mortality is based on baseline population, while serious adverse events and non-serious adverse events are based on the safety population.