Trial Outcomes & Findings for Combination Therapy With Nivolumab and PD-L1/IDO Peptide Vaccine to Patients With Metastatic Melanoma (NCT NCT03047928)

Last Updated: 2025-02-20

Results Overview

Determine the safety of the combination therapy of Nivolumab and the PD-L1/IDO peptide vaccine for patients with metastatic melanoma by reporting adverse events according to CTCAE v. 4.0.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

48 participants

Primary outcome timeframe

0 - 75 weeks

Results posted on

2025-02-20

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity
Overall Study STARTED	30	14	4
Overall Study COMPLETED	30	10	4
Overall Study NOT COMPLETED	0	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity
Overall Study Adverse Event	0	2	0
Overall Study Protocol Violation	0	1	0
Overall Study included in another protocol	0	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A n=30 Participants Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B n=14 Participants Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C n=4 Participants Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity	Total n=48 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=30 Participants	0 Participants n=14 Participants	0 Participants n=4 Participants	0 Participants n=48 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=30 Participants	5 Participants n=14 Participants	1 Participants n=4 Participants	13 Participants n=48 Participants
Age, Categorical >=65 years	23 Participants n=30 Participants	9 Participants n=14 Participants	3 Participants n=4 Participants	35 Participants n=48 Participants
Sex: Female, Male Female	14 Participants n=30 Participants	8 Participants n=14 Participants	2 Participants n=4 Participants	24 Participants n=48 Participants
Sex: Female, Male Male	16 Participants n=30 Participants	6 Participants n=14 Participants	2 Participants n=4 Participants	24 Participants n=48 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Denmark	30 Participants n=30 Participants	14 Participants n=14 Participants	4 Participants n=4 Participants	48 Participants n=48 Participants

PRIMARY outcome

Timeframe: 0 - 75 weeks

Population: Adverse Events recorded for all patients

Determine the safety of the combination therapy of Nivolumab and the PD-L1/IDO peptide vaccine for patients with metastatic melanoma by reporting adverse events according to CTCAE v. 4.0.

Outcome measures

Outcome measures
Measure	Arm A n=30 Participants Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B n=10 Participants Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C n=4 Participants Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity
Number of Participants With Adverse Events	30 Participants	10 Participants	4 Participants

SECONDARY outcome

Timeframe: The patients were evaluated every 12 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months

Population: Overall response rate (ORR)

Clinical response will be evaluated by RECIST and PERCIST 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by PET-CT scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Arm A n=30 Participants Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B n=10 Participants Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C n=4 Participants Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity
Objective Response Rate	24 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: The patients were evaluated from the date of first study treatment until the date of death from any cause, assessed up to 58 months

Overall survival (OS) defined as the time from treatment until death or end of follow-up

Outcome measures

Outcome measures
Measure	Arm A n=30 Participants Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B n=10 Participants Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C n=4 Participants Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity
Overall Survival	NA months Interval 36.4 to The median and upper limit of the 95% confidence interval were not reached due to insufficient number of participants with events. 95% CI, 36.4 to not reached.	16.7 months Interval 4.13 to The upper limit of the 95% confidence interval was not reached due to insufficient number of participants with events. 95% CI, 4.13 to not reached	NA months The dataset is too small to analyze statistically. The median and upper limit of the 95% confidence interval were not evaluated due to insufficient number of participants with events

SECONDARY outcome

Timeframe: The patients were evaluated from date of first study treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months

Population: Only four of ten participants were treated in this cohort. The data was not analyzed due to early termination of the trial cohort

Progression free survival (PFS) defined as the time from treatment initiation to disease progression, relapse or death due to any cause, which ever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Arm A n=30 Participants Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B n=10 Participants Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C n=4 Participants Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity
Progression Free Survival	25.5 months Interval 8.8 to 39.0	2.4 months Interval 1.38 to 2.52	NA months The dataset is too small to analyze statistically. The median and upper limit of the 95% confidence interval were not calculated due to insufficient number of participants with events

SECONDARY outcome

Timeframe: At baseline and up to 24 months after inclusion

Population: Arm A: 30 patients had blood samples available for analysis Arm B: 6/10 patients had blood samples available for analysis Arm C: 1/4 patients had blood samples available for analysis

Number of patients with a significant increase of vaccine-specific T cells in the blood during vaccination, assessed by the presence of vaccine-specific responses in peripheral blood mononuclear cells (PBMCs) before, on and after vaccination using a modified interferon (IFN)-γ enzyme-linked immune absorbent spot (ELISPOT) assay.

Outcome measures

Outcome measures
Measure	Arm A n=30 Participants Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B n=6 Participants Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C n=1 Participants Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity
Evaluation of Vaccine-specific Responses in Peripheral Blood Mononuclear Cells (PBMCs)	28 Participants	2 Participants	1 Participants

Adverse Events

Arm A

Serious events: 11 serious events

Other events: 30 other events

Deaths: 12 deaths

Arm B

Serious events: 2 serious events

Other events: 13 other events

Deaths: 6 deaths

Arm C

Serious events: 1 serious events

Other events: 4 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Prof. MD, Inge Marie Svane

CCIT-DK

Phone: 38683868

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A n=30 participants at risk Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody treatment is not allowed.	Arm B n=14 participants at risk Extension cohort (10 patients). Progressive disease ON anti-PD-1 antibody monotherapy. Subjects should not have experienced serious and/or life-threatening toxicity to antibody therapy.	Arm C n=4 participants at risk Extension cohort (10 patients). Progressive disease during follow up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 antibody therapy. Subjects should not have discontinued antibody therapy due to serious and/or life-threatening toxicity
Cardiac disorders Myocarditis	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tonsillar disorder	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Vascular disorders Vasculitis	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Respiratory, thoracic and mediastinal disorders pneumonitis	6.7% 2/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Respiratory, thoracic and mediastinal disorders Pneumonia	6.7% 2/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Nervous system disorders Cerebellar embolism	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Gastrointestinal disorders Gallbladder disorder	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Gastrointestinal disorders Melaena	0.00% 0/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	25.0% 1/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Gastrointestinal disorders Colitis	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Gastrointestinal disorders Hepatitis	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Musculoskeletal and connective tissue disorders Hip fracture	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Endocrine disorders Adrenal insufficiency	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Endocrine disorders Hypophysitis	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	7.1% 1/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Endocrine disorders Inappropriate antidiuretic hormone secretion	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Infections and infestations Staphylococcal infection	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	25.0% 1/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Infections and infestations Erysipelas	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Infections and infestations Bacteraemia	0.00% 0/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	7.1% 1/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks
Infections and infestations Sepsis	3.3% 1/30 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/14 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks	0.00% 0/4 • All-Cause Mortality, Serious Adverse Events and Other Adverse Events were assessed every 2nd week during treatment and every 3 months during follow-up. All-Cause Mortality was assessed up to 58 months. Serious and Other Adverse Events were assessed up to 75 weeks