Trial Outcomes & Findings for Efficacy and Safety of LNP023 Compared With Rituximab in Subjects With Idiopathic Membranous Nephropathy (NCT NCT04154787)

Last Updated: 2024-10-09

Results Overview

The primary endpoint of this study is the ratio between UPCR at 24 weeks of treatment measured in 24h urine and baseline UPCR . To assess the primary objective, the log-transformed ratio to baseline in UPCR was analyzed using a mixed model for repeated measures (MMRM). The results were back transformed and presented on the original scale.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

Baseline, Day 113, Day 169

Results posted on

2024-10-09

Participant Flow

Participants took part in 18 investigative sites in 9 countries/regions: Argentina (3), Czech Republic (1), Germany (4), India (2), Netherlands (1), Spain (2), United Kingdom (3), China (1) and Taiwan (1)

Participant milestones

Participant milestones
Measure	LNP023 10/50 mg b.i.d. As per protocol V00, participants took LNP023 10 mg orally b.i.d. for 4 weeks followed by LNP023 50 mg orally b.i.d. for 20 weeks	LNP023 200 mg b.i.d. Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab Rituximab 1 g i.v. at Day 1 and Day 15
Overall Study STARTED	3	19	15
Overall Study COMPLETED	3	9	14
Overall Study NOT COMPLETED	0	10	1

Reasons for withdrawal

Reasons for withdrawal
Measure	LNP023 200 mg b.i.d. Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab Rituximab 1 g i.v. at Day 1 and Day 15
Overall Study Adverse Event	1	0
Overall Study Patient Requires Other Treatment	1	0
Overall Study Study Terminated By Sponsor	6	1
Overall Study Subject Decision	1	0
Overall Study Suspected Lack Of Efficacy	1	0

Baseline Characteristics

Efficacy and Safety of LNP023 Compared With Rituximab in Subjects With Idiopathic Membranous Nephropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LNP023 10/50 mg b.i.d. n=3 Participants As per protocol V00, participants took LNP023 10 mg orally b.i.d. for 4 weeks followed by LNP023 50 mg orally b.i.d. for 20 weeks	LNP023 200 mg b.i.d. n=19 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=15 Participants Rituximab 1 g i.v. at Day 1 and Day 15	Total n=37 Participants Total of all reporting groups
Age, Continuous	55.0 years STANDARD_DEVIATION 18.52 • n=5 Participants	48.9 years STANDARD_DEVIATION 8.84 • n=7 Participants	46.7 years STANDARD_DEVIATION 15.33 • n=5 Participants	48.5 years STANDARD_DEVIATION 12.43 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	15 Participants n=7 Participants	14 Participants n=5 Participants	31 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized Black Or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	14 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Day 113, Day 169

Population: PD set: In line with the protocol, PD (pharmacodynamics) analyses were performed for all participants who received LNP023 200 mg or rituximab and experienced no protocol deviations with relevant impact on PD/efficacy data. Only participants with a value for UPCR at both Baseline and Day 113 or Day 169 were included in the analysis.

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=10 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=13 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Ratio Between Baseline Urine Protein Creatinine Ratio (UPCR) and Urine Protein Creatinine Ratio at 24 Weeks of Treatment (From 24h Urine Collection) Day 113	0.94 ratio to baseline Interval 0.74 to 1.2	0.89 ratio to baseline Interval 0.71 to 1.1	—	—	—
Ratio Between Baseline Urine Protein Creatinine Ratio (UPCR) and Urine Protein Creatinine Ratio at 24 Weeks of Treatment (From 24h Urine Collection) Day 169	0.88 ratio to baseline Interval 0.65 to 1.19	0.64 ratio to baseline Interval 0.48 to 0.86	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 15, Day 29, Day 57, Day 113 and Day 169

Population: PD set: In line with the protocol, PD (pharmacodynamics) analyses were performed for all participants who received LNP023 200 mg or rituximab and experienced no protocol deviations with relevant impact on PD/efficacy data. Only participants with values of plasma levels of circulating fragment of factor B at both Baseline and the different time points were included in the analysis.

The drug (LNP023) is expected to block the complement alternative pathway dysregulation and thereby should normalize complement biomarker levels in serum. Bb is a biomarker that accurately reflects the level of complement Alternative Pathway activation. Baseline is defined as the last non-missing measurement prior to randomization. Measurements for LNP023 group were done pre-dose.

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=17 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=13 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) Day 15	1520.59 ng/mL Standard Deviation 9370.086	-417.69 ng/mL Standard Deviation 701.667	—	—	—
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) Day 29	-732.00 ng/mL Standard Deviation 1412.633	-318.46 ng/mL Standard Deviation 604.440	—	—	—
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) Day 57	-545.00 ng/mL Standard Deviation 1379.201	-75.38 ng/mL Standard Deviation 787.545	—	—	—
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) Day 113	-877.27 ng/mL Standard Deviation 1562.716	-219.17 ng/mL Standard Deviation 703.568	—	—	—
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) Day 169	-984.00 ng/mL Standard Deviation 1794.419	-570.00 ng/mL Standard Deviation 611.167	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 15, Day 29, Day 57, Day 113, Day 169

Population: PD set: In line with the protocol, PD (pharmacodynamics) analyses were performed for all participants who received LNP023 200 mg or rituximab and experienced no protocol deviations with relevant impact on PD/efficacy data. Only participants with a value of plasma levels of sC5b-9 at both Baseline and the different time points were included in the analysis.

Soluble C5b-9 (sC5b-9) is a biomarker of the complement pathway activity that correlate with disease progression. Baseline is defined as the last non-missing measurement prior to randomization. Measurements for LNP023 group were done pre-dose.

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=17 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=13 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Change From Baseline in Plasma Levels of sC5b-9 Day 15	-80.40 ng/mL Standard Deviation 98.229	-38.49 ng/mL Standard Deviation 52.258	—	—	—
Change From Baseline in Plasma Levels of sC5b-9 Day 29	-82.80 ng/mL Standard Deviation 118.338	-24.51 ng/mL Standard Deviation 94.826	—	—	—
Change From Baseline in Plasma Levels of sC5b-9 Day 57	-90.62 ng/mL Standard Deviation 108.483	-14.02 ng/mL Standard Deviation 107.651	—	—	—
Change From Baseline in Plasma Levels of sC5b-9 Day 113	-113.32 ng/mL Standard Deviation 108.118	-24.95 ng/mL Standard Deviation 128.721	—	—	—
Change From Baseline in Plasma Levels of sC5b-9 Day 169	-84.07 ng/mL Standard Deviation 96.045	-21.76 ng/mL Standard Deviation 122.654	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 266 and Day 378

Population: PD set: In line with the protocol, PD (pharmacodynamics) analyses were performed for all participants who received LNP023 200 mg or rituximab and experienced no protocol deviations with relevant impact on PD/efficacy data. Only participants with a value of UPCR measured in first morning void at the different time points were included in the analysis.

Adjusted geometric mean ratio to baseline of Urine Protein Creatinine Ratio (UPCR) measured in first morning void. First morning void urine sample was collected in the morning of the day before the visit and kept in the fridge.

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=18 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=13 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 15	0.94 ratio to baseline Interval 0.65 to 1.34	1.15 ratio to baseline Interval 0.75 to 1.76	—	—	—
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 29	0.98 ratio to baseline Interval 0.7 to 1.36	0.90 ratio to baseline Interval 0.6 to 1.35	—	—	—
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 57	1.02 ratio to baseline Interval 0.71 to 1.48	0.77 ratio to baseline Interval 0.51 to 1.16	—	—	—
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 85	1.03 ratio to baseline Interval 0.68 to 1.56	0.75 ratio to baseline Interval 0.5 to 1.13	—	—	—
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 113	1.05 ratio to baseline Interval 0.68 to 1.63	0.92 ratio to baseline Interval 0.6 to 1.41	—	—	—
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 141	0.75 ratio to baseline Interval 0.48 to 1.19	0.77 ratio to baseline Interval 0.48 to 1.23	—	—	—
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 169	0.72 ratio to baseline Interval 0.44 to 1.16	0.55 ratio to baseline Interval 0.34 to 0.89	—	—	—
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 266	0.57 ratio to baseline Interval 0.33 to 0.99	0.34 ratio to baseline Interval 0.2 to 0.57	—	—	—
Ratio to Baseline of Urine Protein Creatinine Ratio (UPCR) Measured in First Morning Void Day 378 (End Of Study)	0.37 ratio to baseline Interval 0.22 to 0.63	0.46 ratio to baseline Interval 0.27 to 0.76	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 169

Population: PD set: In line with the protocol, PD (pharmacodynamics) analyses were performed for all participants who received LNP023 200 mg or rituximab and experienced no protocol deviations with relevant impact on PD/efficacy data. Only participants with UP values at both baseline and Day 169 were included in the analysis.

Participants were considered complete responders if at 24 weeks of treatment, they showed complete remission of proteinuria (i.e., Urine Protein (UP) ≤ 0.3 g/24h), partial responders if they showed partial remission (i.e., UP \> 0.3g/24h and ≤ 3.5 g/24h and a reduction of UP by \>50% from baseline), and non-responders if UP \>3.5g/24h and/or reduction of UP from baseline \<50%.

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=9 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=9 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Number of Participants by Treatment Response at 24 Weeks of Treatment Complete	0 Participants	0 Participants	—	—	—
Number of Participants by Treatment Response at 24 Weeks of Treatment Partial	2 Participants	2 Participants	—	—	—
Number of Participants by Treatment Response at 24 Weeks of Treatment No response	7 Participants	7 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Population: PD set: In line with the protocol, PD (pharmacodynamics) analyses were performed for all participants who received LNP023 200 mg or rituximab and experienced no protocol deviations with relevant impact on PD/efficacy data. Only participants with a eGFR value at both Baseline and the different time points were included in the analysis.

Changes in renal function were assessed via estimated glomerular filtration rate (eGFR). Change in eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=19 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=13 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Change From Baseline in (eGFR) Estimated Glomerular Filtration Rate Over Time Day 15	2.3 mL/min/1.73 m^2 Standard Deviation 12.07	0.3 mL/min/1.73 m^2 Standard Deviation 8.33	—	—	—
Change From Baseline in (eGFR) Estimated Glomerular Filtration Rate Over Time Day 29	-0.5 mL/min/1.73 m^2 Standard Deviation 8.53	6.1 mL/min/1.73 m^2 Standard Deviation 10.44	—	—	—
Change From Baseline in (eGFR) Estimated Glomerular Filtration Rate Over Time Day 57	2.0 mL/min/1.73 m^2 Standard Deviation 11.10	9.2 mL/min/1.73 m^2 Standard Deviation 21.05	—	—	—
Change From Baseline in (eGFR) Estimated Glomerular Filtration Rate Over Time Day 85	-1.6 mL/min/1.73 m^2 Standard Deviation 11.53	10.2 mL/min/1.73 m^2 Standard Deviation 16.40	—	—	—
Change From Baseline in (eGFR) Estimated Glomerular Filtration Rate Over Time Day 113	1.2 mL/min/1.73 m^2 Standard Deviation 8.64	10.8 mL/min/1.73 m^2 Standard Deviation 15.41	—	—	—
Change From Baseline in (eGFR) Estimated Glomerular Filtration Rate Over Time Day 141	-1.8 mL/min/1.73 m^2 Standard Deviation 9.10	7.1 mL/min/1.73 m^2 Standard Deviation 9.29	—	—	—
Change From Baseline in (eGFR) Estimated Glomerular Filtration Rate Over Time Day 169	-1.3 mL/min/1.73 m^2 Standard Deviation 7.36	3.1 mL/min/1.73 m^2 Standard Deviation 13.21	—	—	—

SECONDARY outcome

Timeframe: Day 29 and Day 113 (pre-dose and 0.25 hours, 0.5 hours, 1 hour 2 hours, 4 hours and 6 hours post dose)

Population: PK set: PK (pharmacokinetic) analysis set included all participants with at least one available valid PK concentration measurement, who received any LNP023 and experienced no protocol deviations with relevant impact on PK data. Only participants with PK values at the different time points were included in the analysis.

Pharmacokinetics of LNP023 : Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (time). Actual sampling time points were considered for the calculation of PK parameters.

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=2 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=3 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) n=10 Participants Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) n=2 Participants Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. n=7 Participants Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Pharmacokinetic Parameter Tmax in Plasma Day 29	2.04 hours Interval 2.0 to 2.08	2.00 hours Interval 1.0 to 4.0	2.03 hours Interval 1.0 to 4.38	—	—
Pharmacokinetic Parameter Tmax in Plasma Day 113	—	—	—	2.05 hours Interval 2.0 to 2.1	1.00 hours Interval 0.25 to 6.0

SECONDARY outcome

Timeframe: Day 29 and Day 113 (pre-dose and 0.25 hours, 0.5 hours, 1 hour 2 hours, 4 hours and 6 hours post dose)

Pharmacokinetics of LNP023: Cmax is the maximum (peak) observed plasma drug concentration after dose administration (mass x volume-1)

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=2 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=3 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) n=10 Participants Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) n=2 Participants Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. n=7 Participants Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Pharmacokinetic Parameter Cmax in Plasma Day 29	1200 ng/mL Standard Deviation 799	2070 ng/mL Standard Deviation 938	2140 ng/mL Standard Deviation 917	—	—
Pharmacokinetic Parameter Cmax in Plasma Day 113	—	—	—	1220 ng/mL Standard Deviation 304	4810 ng/mL Standard Deviation 2850

SECONDARY outcome

Timeframe: Day 29 and Day 113 (pre-dose and 0.25 hours, 0.5 hours, 1 hour 2 hours, 4 hours and 6 hours post dose)

Pharmacokinetics of LNP023: AUClast is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1)

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=2 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=3 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) n=10 Participants Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) n=2 Participants Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. n=7 Participants Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Pharmacokinetic Parameter AUClast in Plasma Day 29	5970 hr*ng/mL Standard Deviation 4150	8140 hr*ng/mL Standard Deviation 3080	9920 hr*ng/mL Standard Deviation 3960	—	—
Pharmacokinetic Parameter AUClast in Plasma Day 113	—	—	—	5940 hr*ng/mL Standard Deviation 989	22200 hr*ng/mL Standard Deviation 15600

SECONDARY outcome

Timeframe: Day 29 and Day 113 (pre-dose and 0.25 hours, 0.5 hours, 1 hour 2 hours, 4 hours and 6 hours post dose)

Pharmacokinetics of LNP023 : AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=2 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=3 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) n=10 Participants Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) n=2 Participants Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. n=7 Participants Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Pharmacokinetic Parameter AUCtau in Plasma Day 29	9850 hr*ng/mL Standard Deviation 5790	12800 hr*ng/mL Standard Deviation 3490	16500 hr*ng/mL Standard Deviation 5920	—	—
Pharmacokinetic Parameter AUCtau in Plasma Day 113	—	—	—	10700 hr*ng/mL Standard Deviation 1640	36800 hr*ng/mL Standard Deviation 26100

SECONDARY outcome

Timeframe: Day 113

Pharmacokinetics of LNP023 in urine: Renal plasma clearance derived from 24 hour urine sample

Outcome measures

Outcome measures
Measure	LNP023 200 mg b.i.d. n=1 Participants Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Rituximab n=7 Participants Rituximab 1 g i.v. at Day 1 and Day 15	LNP023 50 mg b.i.d. (4-week Administration) Under Protocol V01, LNP023 50mg taken orally b.i.d. during the first 4 weeks of treatment	LNP023 50 mg b.i.d. (20-week Administration) Under Protocol V00, LNP023 50mg taken orally b.i.d. during the last 20 weeks of treatment	LNP023 200 mg b.i.d. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.
Pharmacokinetics in Urine: Renal Plasma Clearance Derived From 24 Hour Urine Sample	0.602 L/hr	1.19 L/hr Standard Deviation 0.668	—	—	—

Adverse Events

LNP023 10/50 mg b.i.d.

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

LNP023 200 mg b.i.d.

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Pooled LNP023

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Rituximab

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Total

Serious events: 7 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LNP023 10/50 mg b.i.d. n=3 participants at risk As per protocol V00, participants took LNP023 10 mg orally b.i.d. for 4 weeks followed by LNP023 50 mg orally b.i.d. for 20 weeks	LNP023 200 mg b.i.d. n=19 participants at risk Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Pooled LNP023 n=22 participants at risk Combination of the LNP023 10/50 mg b.i.d., 25/200 mg b.i.d. and 50/200 mg b.i.d. groups.	Rituximab n=15 participants at risk Rituximab 1 g i.v. at Day 1 and Day 15	Total n=37 participants at risk Total
Infections and infestations COVID-19 pneumonia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Infections and infestations Lower respiratory tract infection	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	13.3% 2/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	8.1% 3/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings

Other adverse events

Other adverse events
Measure	LNP023 10/50 mg b.i.d. n=3 participants at risk As per protocol V00, participants took LNP023 10 mg orally b.i.d. for 4 weeks followed by LNP023 50 mg orally b.i.d. for 20 weeks	LNP023 200 mg b.i.d. n=19 participants at risk Combination of the LNP023 25/200 mg b.i.d. and 50/200 mg b.i.d. groups. Under protocol V00, participants took LNP023 25 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks. Under protocol v01, participants took LNP023 50 mg orally b.i.d. for 4 weeks followed by LNP023 200 mg orally b.i.d. for 20 weeks.	Pooled LNP023 n=22 participants at risk Combination of the LNP023 10/50 mg b.i.d., 25/200 mg b.i.d. and 50/200 mg b.i.d. groups.	Rituximab n=15 participants at risk Rituximab 1 g i.v. at Day 1 and Day 15	Total n=37 participants at risk Total
Infections and infestations Ear infection	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Infections and infestations Influenza	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Infections and infestations Lower respiratory tract infection	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Infections and infestations Nasopharyngitis	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	13.3% 2/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	8.1% 3/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Infections and infestations Pneumonia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Infections and infestations Respiratory tract infection viral	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Injury, poisoning and procedural complications Fall	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Injury, poisoning and procedural complications Head injury	33.3% 1/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Injury, poisoning and procedural complications Limb injury	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Investigations Alanine aminotransferase increased	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Investigations Liver function test increased	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Metabolism and nutrition disorders Gout	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	13.3% 2/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.4% 2/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	10.5% 2/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	9.1% 2/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	8.1% 3/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Metabolism and nutrition disorders Vitamin B12 deficiency	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	10.5% 2/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	9.1% 2/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.4% 2/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Musculoskeletal and connective tissue disorders Bone hypertrophy	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Musculoskeletal and connective tissue disorders Muscle spasms	33.3% 1/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	9.1% 2/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	8.1% 3/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Nervous system disorders Dizziness	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	10.5% 2/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	9.1% 2/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.4% 2/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Nervous system disorders Headache	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	15.8% 3/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	13.6% 3/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	8.1% 3/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Nervous system disorders Hypersomnia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Nervous system disorders Syncope	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Psychiatric disorders Sleep disorder	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Renal and urinary disorders Nephrotic syndrome	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Reproductive system and breast disorders Epididymal cyst	33.3% 1/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Vascular disorders Hypertension	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Blood and lymphatic system disorders Lymphopenia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Endocrine disorders Hypothyroidism	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Gastrointestinal disorders Abdominal pain lower	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.4% 2/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Gastrointestinal disorders Epigastric discomfort	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Gastrointestinal disorders Inguinal hernia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
General disorders Chest pain	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
General disorders Fatigue	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	10.5% 2/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	9.1% 2/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.4% 2/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
General disorders Influenza like illness	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
General disorders Oedema	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
General disorders Oedema peripheral	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	10.5% 2/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	9.1% 2/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.4% 2/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
General disorders Pyrexia	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	0.00% 0/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	2.7% 1/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Infections and infestations COVID-19	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	15.8% 3/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	13.6% 3/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	10.8% 4/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings
Infections and infestations Coronavirus infection	0.00% 0/3 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.3% 1/19 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	4.5% 1/22 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	6.7% 1/15 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings	5.4% 2/37 • Adverse events were reported from first dose of study treatment until end of study treatment plus 29 weeks post treatment, up to maximum duration of 53 weeks. The LNP023 200mg group is the sum of subjects from v00 (25/200mg, n=4) and v01 (50/200mg, n=15). A separation by subgroup was not justified as Part A doses were similar (25 vs 50mg), short-termed (4 weeks) and below levels expected to be efficacious, while the Part B dose of 200 mg was the same for all for up to 20 weeks. Moreover, if separated, the difference in subject numbers may have carried a risk of under- or over-interpretation of findings

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

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