Trial Outcomes & Findings for Study of Efficacy and Safety of Investigational Treatments in Patients With Moderate to Severe Hidradenitis Suppurativa (NCT NCT03827798)

NCT ID: NCT03827798

Last Updated: 2026-02-06

Results Overview

sHiSCR was defined as at least a 50 percent (%) reduction in abscess and inflammatory nodule (AN) counts, and no increase in draining fistula count related to baseline. The primary variable was modeled with the binomial distribution. A neutral non-informative Beta (1/3, 1/3) distribution was used as the prior for the response rate for all treatment groups. Based on the priors and the observed primary outcome, posterior distributions for the response rate for the investigational treatment and pooled placebo groups were computed respectively. At the time of the statistical comparison for cohorts A, B, and C, the placebo data for cohorts D and E were incomplete and therefore excluded. Similarly, during the comparison for cohort D, the placebo data for cohort E was still pending and was not included.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 248 participants
• Primary outcome timeframe: Baseline, Week 16
• Results posted on: 2026-02-06

Participant Flow

Participants took part in 36 investigative sites in 11 countries.

The study consisted of a screening period of up to 35 days. After last dose of study treatment patients could enter the post-treatment follow-up.

Participant milestones

Measure	Cohort E - Placebo to VAY736 Placebo administered s.c every 4 weeks until Week 13.	Cohort A - CFZ533 600 mg CFZ533 600 mg administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort A - Placebo to CFZ533 Placebo administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort B - LYS006 20 mg LYS006 20 mg administered orally twice per day until Week 16.	Cohort B - Placebo to LYS006 Placebo administered orally twice per day until Week 16.	Cohort C - MAS825 300 mg MAS825 300 mg administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Cohort C - Placebo to MAS825 Placebo administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Cohort D - LOU064 25 mg LOU064 25 mg administered orally twice per day until Week 16.	Cohort D - LOU064 100 mg LOU064 100 mg administered orally twice per day until Week 16.	Cohort D - Placebo to LOU064 Placebo administered orally twice per day until Week 16.	Cohort E - VAY736 300 mg VAY736 300 mg administered s.c every 4 weeks until Week 13.
Treatment Epoch NOT COMPLETED	1	4	4	7	4	4	1	4	7	3	9
Treatment Epoch STARTED	11	29	16	27	13	33	10	33	33	11	32
Treatment Epoch COMPLETED	10	25	12	20	9	29	9	29	26	8	23
Entered Post-treatment Follow-up STARTED	10	26	12	21	9	28	9	30	27	8	23
Entered Post-treatment Follow-up COMPLETED	1	24	11	19	8	26	7	30	25	8	0
Entered Post-treatment Follow-up NOT COMPLETED	9	2	1	2	1	2	2	0	2	0	23

Reasons for withdrawal

Measure	Cohort E - Placebo to VAY736 Placebo administered s.c every 4 weeks until Week 13.	Cohort A - CFZ533 600 mg CFZ533 600 mg administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort A - Placebo to CFZ533 Placebo administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort B - LYS006 20 mg LYS006 20 mg administered orally twice per day until Week 16.	Cohort B - Placebo to LYS006 Placebo administered orally twice per day until Week 16.	Cohort C - MAS825 300 mg MAS825 300 mg administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Cohort C - Placebo to MAS825 Placebo administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Cohort D - LOU064 25 mg LOU064 25 mg administered orally twice per day until Week 16.	Cohort D - LOU064 100 mg LOU064 100 mg administered orally twice per day until Week 16.	Cohort D - Placebo to LOU064 Placebo administered orally twice per day until Week 16.	Cohort E - VAY736 300 mg VAY736 300 mg administered s.c every 4 weeks until Week 13.
Treatment Epoch Adverse Event	0	1	1	1	1	1	0	0	3	0	0
Treatment Epoch Physician Decision	0	1	0	1	2	1	0	0	0	0	0
Treatment Epoch Protocol Deviation	0	0	0	1	0	0	0	0	0	0	0
Treatment Epoch Withdrawal by Subject	1	2	3	4	1	2	1	4	3	2	8
Treatment Epoch Lost to Follow-up	0	0	0	0	0	0	0	0	1	1	1
Entered Post-treatment Follow-up Follow up ongoing	9	0	0	0	0	0	0	0	0	0	21
Entered Post-treatment Follow-up Lost to Follow-up	0	1	0	1	1	2	0	0	2	0	0
Entered Post-treatment Follow-up Withdrawal by Subject	0	1	1	1	0	0	2	0	0	0	2

Baseline Characteristics

Study of Efficacy and Safety of Investigational Treatments in Patients With Moderate to Severe Hidradenitis Suppurativa

Baseline characteristics by cohort

Measure	Cohort A - CFZ533 600 mg n=29 Participants CFZ533 600 mg administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort A - Placebo to CFZ533 n=16 Participants Placebo administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort B - LYS006 20 mg n=27 Participants LYS006 20 mg administered orally twice per day until Week 16.	Cohort B - Placebo to LYS006 n=13 Participants Placebo administered orally twice per day until Week 16.	Cohort C - MAS825 300 mg n=33 Participants MAS825 300 mg administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Cohort C - Placebo to MAS825 n=10 Participants Placebo administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Cohort D - LOU064 25 mg n=33 Participants LOU064 25 mg administered orally twice per day until Week 16.	Cohort D - LOU064 100 mg n=33 Participants LOU064 100 mg administered orally twice per day until Week 16.	Cohort D - Placebo to LOU064 n=11 Participants Placebo administered orally twice per day until Week 16.	Cohort E - VAY736 300 mg n=32 Participants VAY736 300 mg administered s.c every 4 weeks until Week 13.	Cohort E - Placebo to VAY736 n=11 Participants Placebo administered s.c every 4 weeks until Week 13.	Total n=248 Participants Total of all reporting groups
Age, Continuous	38.0 years STANDARD_DEVIATION 8.68 • n=192 Participants	41.4 years STANDARD_DEVIATION 9.54 • n=170 Participants	36.4 years STANDARD_DEVIATION 9.62 • n=185 Participants	36.5 years STANDARD_DEVIATION 13.29 • n=177 Participants	39.5 years STANDARD_DEVIATION 8.22 • n=172 Participants	36.9 years STANDARD_DEVIATION 10.26 • n=896 Participants	35.6 years STANDARD_DEVIATION 10.84 • n=3 Participants	35.3 years STANDARD_DEVIATION 10.99 • n=6 Participants	44.1 years STANDARD_DEVIATION 7.83 • n=6 Participants	34.6 years STANDARD_DEVIATION 8.35 • n=35 Participants	33.1 years STANDARD_DEVIATION 11.26 • n=19 Participants	37.0 years STANDARD_DEVIATION 9.94 • n=20 Participants
Sex: Female, Male Female	16 Participants n=192 Participants	10 Participants n=170 Participants	17 Participants n=185 Participants	7 Participants n=177 Participants	19 Participants n=172 Participants	3 Participants n=896 Participants	18 Participants n=3 Participants	20 Participants n=6 Participants	3 Participants n=6 Participants	17 Participants n=35 Participants	4 Participants n=19 Participants	134 Participants n=20 Participants
Sex: Female, Male Male	13 Participants n=192 Participants	6 Participants n=170 Participants	10 Participants n=185 Participants	6 Participants n=177 Participants	14 Participants n=172 Participants	7 Participants n=896 Participants	15 Participants n=3 Participants	13 Participants n=6 Participants	8 Participants n=6 Participants	15 Participants n=35 Participants	7 Participants n=19 Participants	114 Participants n=20 Participants
Race/Ethnicity, Customized Asian · Asian	1 Participants n=192 Participants	0 Participants n=170 Participants	1 Participants n=185 Participants	0 Participants n=177 Participants	0 Participants n=172 Participants	0 Participants n=896 Participants	0 Participants n=3 Participants	1 Participants n=6 Participants	0 Participants n=6 Participants	1 Participants n=35 Participants	0 Participants n=19 Participants	4 Participants n=20 Participants
Race/Ethnicity, Customized Asian · Black Or African American	1 Participants n=192 Participants	1 Participants n=170 Participants	1 Participants n=185 Participants	0 Participants n=177 Participants	1 Participants n=172 Participants	0 Participants n=896 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants	1 Participants n=6 Participants	5 Participants n=35 Participants	1 Participants n=19 Participants	13 Participants n=20 Participants
Race/Ethnicity, Customized Asian · Other	1 Participants n=192 Participants	0 Participants n=170 Participants	1 Participants n=185 Participants	0 Participants n=177 Participants	5 Participants n=172 Participants	0 Participants n=896 Participants	2 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=35 Participants	0 Participants n=19 Participants	9 Participants n=20 Participants
Race/Ethnicity, Customized Asian · Unknown	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants	0 Participants n=177 Participants	1 Participants n=172 Participants	0 Participants n=896 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=35 Participants	0 Participants n=19 Participants	1 Participants n=20 Participants
Race/Ethnicity, Customized Asian · White	26 Participants n=192 Participants	15 Participants n=170 Participants	24 Participants n=185 Participants	13 Participants n=177 Participants	26 Participants n=172 Participants	10 Participants n=896 Participants	30 Participants n=3 Participants	31 Participants n=6 Participants	10 Participants n=6 Participants	26 Participants n=35 Participants	10 Participants n=19 Participants	221 Participants n=20 Participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: The Pharmacodynamic (PD) analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD data.

sHiSCR was defined as at least a 50 percent (%) reduction in abscess and inflammatory nodule (AN) counts, and no increase in draining fistula count related to baseline. The primary variable was modeled with the binomial distribution. A neutral non-informative Beta (1/3, 1/3) distribution was used as the prior for the response rate for all treatment groups. Based on the priors and the observed primary outcome, posterior distributions for the response rate for the investigational treatment and pooled placebo groups were computed respectively. At the time of the statistical comparison for cohorts A, B, and C, the placebo data for cohorts D and E were incomplete and therefore excluded. Similarly, during the comparison for cohort D, the placebo data for cohort E was still pending and was not included.

Outcome measures

Measure	Cohort A - CFZ533 600 mg n=29 Participants CFZ533 600 mg administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort B - LYS006 20 mg n=25 Participants LYS006 20 mg administered orally twice per day until Week 16.	Cohort C - MAS825 300 mg n=32 Participants MAS825 300 mg administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Pooled Placebo (Cohorts A, B and C) n=39 Participants Placebo to CFZ533, LYS006 and MAS825.	Cohort D - LOU064 25 mg n=33 Participants LOU064 25 mg administered orally twice per day until Week 16.	Cohort D - LOU064 100 mg n=33 Participants LOU064 100 mg administered orally twice per day until Week 16.	Pooled Placebo (Cohorts A, B, C and D) n=49 Participants Placebo to CFZ533, LYS006, MAS825 and LOU064.	Cohort E - VAY736 300 mg n=31 Participants VAY736 300 mg administered s.c every 4 weeks until Week 13.	Pooled Placebo (Cohorts A, B, C, D and E) n=60 Participants Placebo to CFZ533, LYS006, MAS825, LOU064 and VAY736.
Percentage of Participants Achieving Clinical Response Measured by Simplified Hidradenitis Suppurativa (sHiSCR)	17 Participants	8 Participants	15 Participants	14 Participants	24 Participants	16 Participants	17 Participants	16 Participants	23 Participants

Adverse Events

Cohort A - CFZ533 600 mg

Serious events: 4 serious events

Other events: 23 other events

Deaths: 0 deaths

Cohort B - LYS006 20 mg

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Cohort C - MAS825 300 mg

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Cohort D - LOU064 25 mg

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Cohort D - LOU064 100 mg

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Cohort E - VAY736 300 mg

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Pooled Placebo (Cohorts A, B, C, D and E)

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Total

Serious events: 11 serious events

Other events: 161 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort A - CFZ533 600 mg n=29 participants at risk CFZ533 600 mg administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort B - LYS006 20 mg n=27 participants at risk LYS006 20 mg administered orally twice per day until Week 16.	Cohort C - MAS825 300 mg n=33 participants at risk MAS825 300 mg administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Cohort D - LOU064 25 mg n=33 participants at risk LOU064 25 mg administered orally twice per day until Week 16.	Cohort D - LOU064 100 mg n=33 participants at risk LOU064 100 mg administered orally twice per day until Week 16.	Cohort E - VAY736 300 mg n=32 participants at risk VAY736 300 mg administered s.c every 4 weeks until Week 13.	Pooled Placebo (Cohorts A, B, C, D and E) n=61 participants at risk Placebo to CFZ533, LYS006, MAS825, LOU064 and VAY736.	Total n=248 participants at risk Total
Gastrointestinal disorders Colitis	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.1% 1/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Abscess limb	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Genital abscess	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Testicular abscess	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations Blood creatine phosphokinase increased	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Psychiatric disorders Depression	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Reproductive system and breast disorders Ovarian cyst	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Reproductive system and breast disorders Testicular torsion	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Vascular disorders Hypertensive crisis	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.40% 1/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.

Other adverse events

Measure	Cohort A - CFZ533 600 mg n=29 participants at risk CFZ533 600 mg administered subcutaneous (s.c) weekly for 4 weeks, followed by bi-weekly until Week 15.	Cohort B - LYS006 20 mg n=27 participants at risk LYS006 20 mg administered orally twice per day until Week 16.	Cohort C - MAS825 300 mg n=33 participants at risk MAS825 300 mg administered s.c. bi-weekly for 4 weeks, followed by monthly until Week 13.	Cohort D - LOU064 25 mg n=33 participants at risk LOU064 25 mg administered orally twice per day until Week 16.	Cohort D - LOU064 100 mg n=33 participants at risk LOU064 100 mg administered orally twice per day until Week 16.	Cohort E - VAY736 300 mg n=32 participants at risk VAY736 300 mg administered s.c every 4 weeks until Week 13.	Pooled Placebo (Cohorts A, B, C, D and E) n=61 participants at risk Placebo to CFZ533, LYS006, MAS825, LOU064 and VAY736.	Total n=248 participants at risk Total
Gastrointestinal disorders Flatulence	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	7.4% 2/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.81% 2/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Gastrointestinal disorders Abdominal pain	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.3% 2/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.4% 6/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Blood and lymphatic system disorders Increased tendency to bruise	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.81% 2/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Gastrointestinal disorders Constipation	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 4/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Gastrointestinal disorders Diarrhoea	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	9.1% 3/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	8.2% 5/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	5.6% 14/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Gastrointestinal disorders Nausea	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.3% 2/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.4% 6/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
General disorders Asthenia	10.3% 3/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.6% 4/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	4.4% 11/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
General disorders Fatigue	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	14.8% 4/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	9.1% 3/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	9.1% 3/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.6% 4/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.5% 16/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
General disorders Pyrexia	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	11.1% 3/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.1% 1/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.6% 4/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	4.8% 12/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Bacteriuria	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 4/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Bronchitis	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	9.4% 3/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.0% 5/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations COVID-19	10.3% 3/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	24.2% 8/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	4.9% 3/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	7.7% 19/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Ear infection	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	7.4% 2/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 4/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Influenza	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.6% 4/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.0% 5/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Nasopharyngitis	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	14.8% 4/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	9.1% 3/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	21.2% 7/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	12.5% 4/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	4.9% 3/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	9.7% 24/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Sinusitis	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	9.1% 3/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.1% 1/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.8% 7/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Tonsillitis	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.81% 2/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Infections and infestations Upper respiratory tract infection	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.3% 2/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.4% 6/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Injury, poisoning and procedural complications Injection related reaction	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	15.6% 5/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.4% 6/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations Bacterial test positive	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 4/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations Blood creatine phosphokinase increased	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.2% 3/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations Blood glucose increased	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.81% 2/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations Blood urine present	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.4% 6/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations C-reactive protein increased	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	4.9% 3/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.8% 7/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations Crystal urine present	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	8.2% 5/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.8% 7/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations Nitrite urine present	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.81% 2/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Investigations Urine albumin/creatinine ratio increased	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	11.1% 3/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.3% 2/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	4.0% 10/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Musculoskeletal and connective tissue disorders Arthralgia	10.3% 3/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.3% 2/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.8% 7/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Musculoskeletal and connective tissue disorders Back pain	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.0% 5/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Musculoskeletal and connective tissue disorders Myalgia	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.1% 1/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 4/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Musculoskeletal and connective tissue disorders Pain in extremity	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.4% 6/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Nervous system disorders Dizziness	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	7.4% 2/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.8% 7/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Nervous system disorders Headache	6.9% 2/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	14.8% 4/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	15.2% 5/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	12.1% 4/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.1% 1/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	9.8% 6/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	8.9% 22/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Psychiatric disorders Depression	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.1% 1/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 4/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Renal and urinary disorders Proteinuria	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.3% 2/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.4% 6/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	7.4% 2/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	2.8% 7/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Skin and subcutaneous tissue disorders Erythema	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 4/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Skin and subcutaneous tissue disorders Hidradenitis	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	7.4% 2/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	15.2% 5/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	18.8% 6/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	13.1% 8/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	8.9% 22/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 1/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	1.6% 4/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Skin and subcutaneous tissue disorders Pruritus	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.1% 1/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	4.9% 3/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.2% 8/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.
Vascular disorders Hypertension	3.4% 1/29 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.7% 1/27 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.0% 1/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.1% 2/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	0.00% 0/33 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	3.1% 1/32 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	6.6% 4/61 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.	4.0% 10/248 • Cohorts A, B and C: 28 weeks including 12 weeks follow up period. Cohort D: 20 weeks including 4 weeks follow up period. Cohort E (ongoing): up to 116 weeks including 100 weeks follow up period.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER