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Clinical Trial Results:
An adaptive seamless randomized, double-blind, placebo-controlled, dose ranging study to investigate the efficacy and safety of LNP023 in primary IgA nephropathy patients

Summary
EudraCT number	2017-000891-27
Trial protocol	GB SE FI DE BE NL DK CZ HU FR IT
Global end of trial date	22 Jun 2021

Results information
Results version number	v1(current)
This version publication date	30 Jun 2022
First version publication date	30 Jun 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CLNP023X2203

ISRCTN number

US NCT number

NCT03373461

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

Novartis Campus, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

Novartis Campus, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

22 Jun 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Jun 2021

Was the trial ended prematurely?

Main objective of the trial

To evaluate the dose response relationship of LNP023 on the reduction in proteinuria versus placebo after 90 days of treatment

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Feb 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 2

Country: Number of subjects enrolled

Australia: 5

Country: Number of subjects enrolled

Belgium: 14

Country: Number of subjects enrolled

Brazil: 4

Country: Number of subjects enrolled

China: 9

Country: Number of subjects enrolled

Colombia: 1

Country: Number of subjects enrolled

Czechia: 1

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

Finland: 1

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

Germany: 5

Country: Number of subjects enrolled

Hong Kong: 2

Country: Number of subjects enrolled

India: 3

Country: Number of subjects enrolled

Israel: 4

Country: Number of subjects enrolled

Japan: 5

Country: Number of subjects enrolled

Korea, Republic of: 1

Country: Number of subjects enrolled

Malaysia: 1

Country: Number of subjects enrolled

Netherlands: 2

Country: Number of subjects enrolled

Norway: 5

Country: Number of subjects enrolled

Singapore: 2

Country: Number of subjects enrolled

Sweden: 3

Country: Number of subjects enrolled

Taiwan: 8

Country: Number of subjects enrolled

Thailand: 14

Country: Number of subjects enrolled

Turkey: 5

Country: Number of subjects enrolled

United Kingdom: 10

Worldwide total number of subjects

112

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

109

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

There were 99 participants screened and 46 randomized participants completed in Part 1. There were 162 screened in Part 2 and 66 were randomized. All participants completed a run-in period of at least 30 days. Participants randomized to Part 1 could not participate in Part 2.

Period 1 title

Part 1 (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

LNP023 10 mg BID

Arm description

10 mg taken twice a day

Arm type

Experimental

Investigational medicinal product name

iptacopan

Investigational medicinal product code

LNP023

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

10 mg taken twice a day

LNP023 50 mg BID

Arm description

50 mg taken twice a day

Arm type

Experimental

Investigational medicinal product name

iptacopan

Investigational medicinal product code

LNP023

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

50 mg taken twice a day

LNP023 100 mg BID - Part 2

Arm description

100 mg taken orally twice a day

Arm type

Experimental

Investigational medicinal product name

iptacopan

Investigational medicinal product code

LNP023

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

100 mg taken twice a day

LNP023 200 mg BID

Arm description

200 mg taken twice a day

Arm type

Experimental

Investigational medicinal product name

iptacopan

Investigational medicinal product code

LNP023

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

200 mg taken twice a day

Placebo

Arm description

Placebo identical to LNP023 taken orally twice a day

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo identical to LNP023 taken twice a day

Number of subjects in period 1	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Started	20	19	22	26	25
Started Part 1	9 ^[1]	8 ^[2]	15 ^[3]	14 ^[4]	14 ^[5]
Completed Part 1	9 ^[6]	8 ^[7]	15 ^[8]	14 ^[9]	14 ^[10]
Started Part 2	11 ^[11]	11 ^[12]	22	11 ^[13]	11 ^[14]
Completed Part 2	11 ^[15]	10 ^[16]	22	11 ^[17]	10 ^[18]
Completed	20	18	22	26	24
Not completed	0	1	0	0	1
Adverse event, non-fatal	-	1	-	-	1

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[15] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[16] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[17] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.
[18] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants randomized to Part 1 could not participate in Part 2.

Baseline characteristics

Top of page

Reporting group title

LNP023 10 mg BID

Reporting group description

10 mg taken twice a day

Reporting group title

LNP023 50 mg BID

Reporting group description

50 mg taken twice a day

Reporting group title

LNP023 100 mg BID - Part 2

Reporting group description

100 mg taken orally twice a day

Reporting group title

LNP023 200 mg BID

Reporting group description

200 mg taken twice a day

Reporting group title

Placebo

Reporting group description

Placebo identical to LNP023 taken orally twice a day

Reporting group values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo	Total
Number of subjects	20	19	22	26	25	112
Age Categorical
Units:
18 years - <65 years	20	19	21	24	25	109
65 years - <85 years	0	0	1	2	0	3
Age Continuous
Units: years
arithmetic mean (standard deviation)	39.2 ± 12.42	36.6 ± 8.42	36.0 ± 13.15	42.5 ± 15.76	39.4 ± 11.00	-
Sex: Female, Male
Units:
Female	11	6	11	11	7	46
Male	9	13	11	15	18	66
Race/Ethnicity, Customized
Units: Subjects
Asian	10	9	12	12	11	54
White	10	9	10	13	13	55
Black or African American	0	1	0	1	0	2
American Indian or Alaska Native	0	0	0	0	1	1
Prior use of ACEi and/or ARB
Prior use of angiotensin converting enzyme inhibitor and/or angiotensin receptor blocker
Units: Subjects
No prior use of ACEi/or ARB	1	0	0	0	0	1
Prior use of ACEi/ARB	19	19	22	26	25	111
Urine Protein to Creatinine Ratio (UPCR)
From 24 hour urine collection
Units: g/mol
arithmetic mean (standard deviation)	214.1 ± 122.29	188.2 ± 90.38	203.4 ± 98.29	151.0 ± 109.46	146.6 ± 61.62	-
Estimated Glomerular Filtration Rate (eGFR)
Units: mL/min/1.73m^2
arithmetic mean (standard deviation)	66.0 ± 28.51	53.8 ± 22.73	67.0 ± 31.75	57.9 ± 28.92	65.7 ± 32.60	-
Supine Blood Pressure
Units: mmHg
arithmetic mean (standard deviation)	134.4 ± 11.65	122.6 ± 12.15	125.0 ± 11.30	125.7 ± 11.65	125.5 ± 11.37	-
Supine Blood Pressure
Units: mmHg
arithmetic mean (standard deviation)	84.1 ± 7.65	76.9 ± 8.41	80.0 ± 10.40	79.7 ± 7.62	78.2 ± 7.32	-

End points

Top of page

Reporting group title

LNP023 10 mg BID

Reporting group description

10 mg taken twice a day

Reporting group title

LNP023 50 mg BID

Reporting group description

50 mg taken twice a day

Reporting group title

LNP023 100 mg BID - Part 2

Reporting group description

100 mg taken orally twice a day

Reporting group title

LNP023 200 mg BID

Reporting group description

200 mg taken twice a day

Reporting group title

Placebo

Reporting group description

Placebo identical to LNP023 taken orally twice a day

Subject analysis set title

<9 rbc/hpf

Subject analysis set type

Full analysis

Subject analysis set description

Low-grade hematuria

Subject analysis set title

>=9 to =<50 rbc/hpf

Subject analysis set type

Full analysis

Subject analysis set description

Intermediate-grade hematuria

Subject analysis set title

>50 rbc/hpf

Subject analysis set type

Full analysis

Subject analysis set description

Higher-grade hematuria

Subject analysis set title

Baseline

Subject analysis set type

Full analysis

Subject analysis set description

Categories of hematuria at baseline

Subject analysis set title

<9 rbc/hpf

Subject analysis set type

Full analysis

Subject analysis set description

Low-grade hematuria

Subject analysis set title

>=9 to =<50 rbc/hpf

Subject analysis set type

Full analysis

Subject analysis set description

Intermediate-grade hematuria

Subject analysis set title

>50 rbc/hpf

Subject analysis set type

Full analysis

Subject analysis set description

Higher-grade hematuria

Primary: MCP-Mod estimates of the ratio to baseline of urine protein to creatinine ratio (UPCR) (g/mol) - Parts 1 and 2 at Day 90

Top of page

End point title

MCP-Mod estimates of the ratio to baseline of urine protein to creatinine ratio (UPCR) (g/mol) - Parts 1 and 2 at Day 90

End point description

For UPCR test, participants collected all of their urine over a 24-hour period. The change from baseline in log transformed (natural log, base of e) UPCR at multiple time points (baseline, day 30, and day 90) was analyzed using a Mixed Model of Repeated Measures (MMRM) model. • The model included treatment, time point (as study day relative to start of study treatment), study part (Part 1 or Part 2), and ancestry (Asian/non-Asian) as fixed effects, and baseline log UPCR as a fixed covariate. The existence of a dose-response relationship was assessed using Multiple Comparison Procedure (MCP-Mod) method. The lower the number of the ratio, the greater the reduction in proteinuria.

End point type

Primary

End point timeframe

Baseline, Days 30 and 90

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	19	19	22	26	25
Units: Ratio to baseline
number (confidence interval 80%)	0.85 (0.77 to 0.93)	0.80 (0.73 to 0.87)	0.76 (0.70 to 0.81)	0.69 (0.61 to 0.77)	0.88 (0.80 to 1.00)

10 mg vs Placebo

Comparison groups

Placebo v LNP023 10 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Ratio of the UPCR ratio to placebo

Point estimate

0.99

Confidence interval

level

80%

sides

2-sided

lower limit

0.86

upper limit

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Ratio of the UPCR ratio to placebo

Point estimate

0.94

Confidence interval

level

80%

sides

2-sided

lower limit

0.76

upper limit

0.98

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Ratio of the UPCR ratio to placebo

Point estimate

0.87

Confidence interval

level

80%

sides

2-sided

lower limit

0.72

upper limit

0.96

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Ratio of the UPCR ratio to placebo

Point estimate

0.77

Confidence interval

level

80%

sides

2-sided

lower limit

0.66

upper limit

0.92

All doses vs placebo

Comparison groups

LNP023 10 mg BID v LNP023 50 mg BID v LNP023 100 mg BID - Part 2 v LNP023 200 mg BID v Placebo

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.038

Method

Multiple comparison procedure-modeling

Confidence interval

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the change from baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90

End point description

eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

End point type

Secondary

End point timeframe

Baseline, Days 8, 15, 30 and 90

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	20	19	22	26	25
Units: mL/min/SSA
arithmetic mean (standard error)	-0.06 ± 1.760	2.49 ± 1.859	0.23 ± 1.821	2.42 ± 1.545	-3.34 ± 1.606

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

3.28

Confidence interval

level

80%

sides

2-sided

lower limit

0.21

upper limit

6.344

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

5.83

Confidence interval

level

80%

sides

2-sided

lower limit

2.642

upper limit

9.01

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

3.56

Confidence interval

level

80%

sides

2-sided

lower limit

0.427

upper limit

6.7

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

5.76

Confidence interval

level

80%

sides

2-sided

lower limit

2.882

upper limit

8.638

Secondary: Shift table from baseline for Hematuria levels - Parts 1 and 2 at Day 90

Top of page

End point title

Shift table from baseline for Hematuria levels - Parts 1 and 2 at Day 90

End point description

Hematuria levels were the number of erythrocytes/high-power-field (hpf) measured through microscopic examination. Levels considered in the analysis were: Low-grade hematuria: <9 rbc/hpf, Intermediate-grade hematuria: >= 9 to <=50 rbc/hpf and Higher-grade hematuria: >50 rbc/hpf.

End point type

Secondary

End point timeframe

Baseline, Days 8, 15, 30 ,60 and 90

End point values	<9 rbc/hpf	>=9 to =<50 rbc/hpf	>50 rbc/hpf
Number of subjects analysed	56	10	1
Units: participants
LNP023 10mg <9	7	1	0
LNP023 10mg >=9 to =<50	1	3	0
LNP023 10mg >50	0	0	0
LNP023 50mg <9	13	0	0
LNP023 50mg >=9 to =<50	1	1	0
LNP023 50mg >50	0	0	0
LNP023 100mg <9	6	0	0
LNP023 100mg >=9 to =<50	4	0	0
LNP023 100mg >50	2	1	0
LNP023 200mg <9	6	0	0
LNP023 200mg >=9 to =<50	6	2	0
LNP023 200mg >50	0	0	0
Placebo <9	6	2	0
Placebo >=9 to =<50	4	0	1
Placebo >50	0	0	0

No statistical analyses for this end point

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24hour urine protein (UP) - Parts 1 and 2 to Day 90

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24hour urine protein (UP) - Parts 1 and 2 to Day 90

End point description

Participants collected all of their urine over a 24-hour period.

End point type

Secondary

End point timeframe

Baseline, Days 30 and 90

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	19	19	22	26	25
Units: Ratio to baseline
geometric mean (confidence interval 80%)	0.80 (0.661 to 0.965)	0.89 (0.740 to 1.070)	0.61 (0.509 to 0.729)	0.70 (0.601 to 0.823)	0.84 (0.713 to 0.987)

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.95

Confidence interval

level

80%

sides

2-sided

lower limit

0.742

upper limit

1.222

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

1.06

Confidence interval

level

80%

sides

2-sided

lower limit

0.83

upper limit

1.356

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.73

Confidence interval

level

80%

sides

2-sided

lower limit

0.569

upper limit

0.928

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.84

Confidence interval

level

80%

sides

2-sided

lower limit

0.669

upper limit

1.05

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline of 24 hour urine albumin (UA) - Parts 1 and 2 to Day 90

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the ratio to baseline of 24 hour urine albumin (UA) - Parts 1 and 2 to Day 90

End point description

Participants collected all of their urine over a 24-hour period.

End point type

Secondary

End point timeframe

Baseline, Days 30 and 90

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	19	19	22	26	25
Units: Ratio to baseline
geometric mean (confidence interval 80%)	0.79 (0.648 to 0.964)	0.93 (0.763 to 1.122)	0.61 (0.504 to 0.734)	0.73 (0.623 to 0.865)	0.82 (0.693 to 0.973)

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.96

Confidence interval

level

80%

sides

2-sided

lower limit

0.741

upper limit

1.25

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

1.13

Confidence interval

level

80%

sides

2-sided

lower limit

0.872

upper limit

1.458

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.74

Confidence interval

level

80%

sides

2-sided

lower limit

0.574

upper limit

0.957

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.89

Confidence interval

level

80%

sides

2-sided

lower limit

0.706

upper limit

1.132

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine albumin to creatinine (UACR) - Parts 1 and 2 to Day 90

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine albumin to creatinine (UACR) - Parts 1 and 2 to Day 90

End point description

Participants collected all of their urine over a 24-hour period.

End point type

Secondary

End point timeframe

Baseline, Days 30 and 90

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	19	19	22	26	25
Units: Ratio to baseline
geometric mean (confidence interval 80%)	0.85 (0.728 to 0.998)	0.89 (0.765 to 1.045)	0.66 (0.567 to 0.772)	0.74 (0.647 to 0.842)	0.87 (0.756 to 0.998)

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.98

Confidence interval

level

80%

sides

2-sided

lower limit

0.794

upper limit

1.214

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

1.03

Confidence interval

level

80%

sides

2-sided

lower limit

0.835

upper limit

1.269

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.76

Confidence interval

level

80%

sides

2-sided

lower limit

0.616

upper limit

0.942

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.85

Confidence interval

level

80%

sides

2-sided

lower limit

0.704

upper limit

1.027

Secondary: Plasma Pharmacokinetics (PK) of Area Under the Curve at steady state (AUCtau,ss and AUClast,ss) at Day 30

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End point title

Plasma Pharmacokinetics (PK) of Area Under the Curve at steady state (AUCtau,ss and AUClast,ss) at Day 30 ^[1]

End point description

AUClast,ss: the area under the plasma concentration-time curve from time zero to last quantifiable concentration at steady state AUCtau,ss: the area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady state

End point type

Secondary

End point timeframe

Baseline (0 hour), Day 30 (0, 0.25, 0.5, 1,2,4,6,8 hours)

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma samples for participants receiving LNP023 treatment

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID
Number of subjects analysed	18	18	16	24
Units: hr*ng/mL
arithmetic mean (standard deviation)
AUClast,ss	5820 ± 1750	13000 ± 2740	18400 ± 6040	27900 ± 9930
AUCtau,ss	8010 ± 2550	17700 ± 4250	24700 ± 8030	37100 ± 13500

No statistical analyses for this end point

Secondary: Plasma Pharmacokinetics (PK) of pre-dose trough at steady state (Ctrough,ss) and maximum concentrations (Cmax,ss) at Day 30

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End point title

Plasma Pharmacokinetics (PK) of pre-dose trough at steady state (Ctrough,ss) and maximum concentrations (Cmax,ss) at Day 30 ^[2]

End point description

Cmax,ss: the observed maximum plasma concentration following drug administration at steady state (ng/mL) Ctrough,ss: the pre-dose plasma concentration observed during a dosing interval at steady state (ng/mL)

End point type

Secondary

End point timeframe

Baseline (0 hour), Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hours)

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma samples for participants receiving LNP023 treatment

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID
Number of subjects analysed	18	18	16	24
Units: hr*ng/mL
arithmetic mean (standard deviation)
Ctrough,ss	515 ± 232	1130 ± 348	1510 ± 567	2200 ± 964
Cmax,ss	964 ± 264	2150 ± 480	3300 ± 1080	4940 ± 1770

No statistical analyses for this end point

Secondary: Plasma Pharmacokinetics (PK) of time to maximum concentration at steady state (Tmax,ss) at Day 30

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End point title

Plasma Pharmacokinetics (PK) of time to maximum concentration at steady state (Tmax,ss) at Day 30 ^[3]

End point description

Tmax,ss: the time to reach the maximum concentration after drug administration at steady state (h)

End point type

Secondary

End point timeframe

Baseline (0 hour), Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hours)

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma samples for participants receiving LNP023 treatment

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID
Number of subjects analysed	18	18	16	24
Units: hour
median (full range (min-max))	2.00 (0.250 to 6.00)	2.00 (1.00 to 6.00)	2.00 (0.500 to 6.00)	2.00 (0.500 to 4.00)

No statistical analyses for this end point

Secondary: Amount of LNP023 excreted into urine (Ae,ss) at Day 30

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End point title

Amount of LNP023 excreted into urine (Ae,ss) at Day 30 ^[4]

End point description

Ae,ss: the total cumulative urinary excretion at steady state

End point type

Secondary

End point timeframe

Baseline and Day 30

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Samples for participants receiving LNP023 treatment

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID
Number of subjects analysed	16	14	14	22
Units: mg
arithmetic mean (standard deviation)	1.72 ± 1.15	11.7 ± 5.84	30.9 ± 17.0	60.3 ± 27.1

No statistical analyses for this end point

Secondary: Percent of LNP023 excreted into urine at Day 30

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End point title

Percent of LNP023 excreted into urine at Day 30 ^[5]

End point description

Percent of drug excreted into the urine

End point type

Secondary

End point timeframe

Baseline and Day 30

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Samples for participants receiving LNP023 treatment

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID
Number of subjects analysed	16	14	14	22
Units: percent of dose
arithmetic mean (standard deviation)	8.59 ± 5.77	11.7 ± 5.84	15.5 ± 8.50	15.1 ± 6.77

No statistical analyses for this end point

Secondary: Renal clearance from plasma at steady state (CLr,ss) at Day 30

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End point title

Renal clearance from plasma at steady state (CLr,ss) at Day 30 ^[6]

End point description

The renal clearance from plasma at steady state

End point type

Secondary

End point timeframe

Baseline and Day 30

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma samples for participants receiving LNP023 treatment

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID
Number of subjects analysed	16	14	14	22
Units: L/hr
arithmetic mean (standard deviation)	0.112 ± 0.0744	0.348 ± 0.179	0.719 ± 0.479	0.942 ± 0.540

No statistical analyses for this end point

Secondary: Change from baseline in plasma levels of circulating fragment of Factor B (Bb) and soluble terminal complement complex (sC5b-9) biomarkers for Parts 1 and 2 to Day 90

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End point title

Change from baseline in plasma levels of circulating fragment of Factor B (Bb) and soluble terminal complement complex (sC5b-9) biomarkers for Parts 1 and 2 to Day 90

End point description

The complement AP biomarkers Bb and sC5b-9 were evaluated as potential pharmacodynamics and mode-of-action markers. Both biomarkers were measured using validated enzyme-linked immunosorbent assays (ELISAs).

End point type

Secondary

End point timeframe

Baseline, Days 8, 15, 30, 60, 90

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	20	19	22	26	25
Units: ng/mL
geometric mean (geometric coefficient of variation)
Day 8 - Bb, n=14,16,13,25,19	76.7 ± 22.89	72.2 ± 22.86	71.4 ± 30.66	66.3 ± 28.15	102.7 ± 19.78
Day 15 - Bb, n=13,14,16,22,22	80.4 ± 32.59	74.1 ± 23.30	77.9 ± 33.28	72.9 ± 20.47	108.6 ± 23.19
Day 30 - Bb, n=16,17,18,26,24	76.4 ± 18.32	76.2 ± 23.62	76.8 ± 34.00	70.4 ± 28.96	99.3 ± 22.07
Day 60 - Bb, n=14,16,17,25,21	78.8 ± 20.26	75.2 ± 19.05	77.4 ± 35.23	72.8 ± 23.97	102.9 ± 24.07
Day 90 - Bb, n=17,16,17,25,21	90.5 ± 25.57	79.3 ± 22.47	77.6 ± 35.42	74.6 ± 23.91	102.7 ± 22.01
Day 8 sCB5b-9, n=12,16,13,22,17	80.6 ± 12.29	69.6 ± 37.40	65.9 ± 24.05	75.8 ± 30.15	95.2 ± 22.01
Day 15 sCB5b-9, n=13,14,16,21,21	79.4 ± 27.60	72.2 ± 33.86	65.9 ± 24.05	78.0 ± 32.06	99.4 ± 25.40
Day 30 sCB5b-9, n=16,17,18,25,24	85.8 ± 23.88	68.6 ± 41.32	76.4 ± 25.97	69.8 ± 21.98	94.2 ± 24.96
Day 60 sCB5b-9, n=14,16,17,24,20	84.6 ± 27.37	73.7 ± 31.99	74.9 ± 29.65	76.2 ± 29.80	95.7 ± 30.11
Day 90 sCB5b-9, n=16,16,17,23,19	89.6 ± 28.66	73.8 ± 36.21	79.0 ± 22.82	75.0 ± 34.21	103.4 ± 21.52

No statistical analyses for this end point

Secondary: Estimation of lowest dose providing maximal reduction of proteinuria

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End point title

Estimation of lowest dose providing maximal reduction of proteinuria

End point description

The log transformation used refers to the natural log (base of e). Results are back-transformed and expressed as geometric means.

End point type

Secondary

End point timeframe

Baseline up to Month 3

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	19	19	22	26	25
Units: g/mol
geometric mean (confidence interval 80%)	0.85 (0.77 to 0.93)	0.80 (0.73 to 0.87)	0.76 (0.70 to 0.81)	0.69 (0.61 to 0.77)	0.88 (0.80 to 1.00)

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Multiple Comparison Procedure (MCP-Mod)

Point estimate

0.99

Confidence interval

level

80%

sides

2-sided

lower limit

0.86

upper limit

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Multiple Comparison Procedure (MCP-Mod)

Point estimate

0.94

Confidence interval

level

80%

sides

2-sided

lower limit

0.76

upper limit

0.98

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Multiple Comparison Procedure (MCP-Mod)

Point estimate

0.87

Confidence interval

level

80%

sides

2-sided

lower limit

0.72

upper limit

0.96

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Multiple Comparison Procedure (MCP-Mod)

Point estimate

0.77

Confidence interval

level

80%

sides

2-sided

lower limit

0.66

upper limit

0.92

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the change from baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180

End point description

eGFR; estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

End point type

Secondary

End point timeframe

Baseline, Days 8, 15, 30, 60, 90, 135 and 180

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	9	10	19	11	11
Units: mL/min/SSA
arithmetic mean (standard error)	0.78 ± 1.977	-2.35 ± 1.995	-2.91 ± 1.359	-1.18 ± 1.798	-3.17 ± 1.868

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

3.95

Confidence interval

level

80%

sides

2-sided

lower limit

0.42

upper limit

7.472

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

0.82

Confidence interval

level

80%

sides

2-sided

lower limit

-2.747

upper limit

4.39

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

0.26

Confidence interval

level

80%

sides

2-sided

lower limit

-2.745

upper limit

3.262

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

1.98

Confidence interval

level

80%

sides

2-sided

lower limit

-1.368

upper limit

5.337

Secondary: Shift table from baseline for Hematuria levels - Part 2 at Day 180

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End point title

Shift table from baseline for Hematuria levels - Part 2 at Day 180

End point description

End point type

Secondary

End point timeframe

Baseline, Days 15, 30, 60, 90, 135 and 180

End point values	Baseline	<9 rbc/hpf	>=9 to =<50 rbc/hpf	>50 rbc/hpf
Number of subjects analysed	9	10	19	11
Units: participants
LNP023 10mg <9	2	1	1	0
LNP023 10mg >=9 to =<50	3	2	1	0
LNP023 10mg >50	0	0	0	0
LNP023 50mg <9	5	5	0	0
LNP023 50mg >=9 to =<50	1	1	0	0
LNP023 50mg >50	0	0	0	0
LNP023 100mg <9	2	2	0	0
LNP023 100mg >=9 to =<50	3	3	0	0
LNP023 100mg >50	3	2	1	0
LNP023 200mg <9	4	4	0	0
LNP023 200mg >=9 to =<50	2	2	0	0
LNP023 200mg >50	0	0	0	0
Placebo <9	4	4	0	0
Placebo >=9 to =<50	1	0	0	1
Placebo >50	0	0	0	0

No statistical analyses for this end point

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline in protein level urine using the urine protein-creatinine ratio (UPCR) from 24 hour urine collection - Part 2 up to Day 180

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the change from baseline in protein level urine using the urine protein-creatinine ratio (UPCR) from 24 hour urine collection - Part 2 up to Day 180

End point description

For UPCR test, participants collected all of their urine over a 24-hour period

End point type

Secondary

End point timeframe

Baseline, Days 30, 90 and 180

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	9	10	19	11	11
Units: mg/d
geometric mean (confidence interval 80%)	1.06 (0.803 to 1.394)	0.59 (0.452 to 0.779)	0.66 (0.540 to 0.798)	0.73 (0.568 to 0.940)	0.91 (0.705 to 1.185)

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

1.16

Confidence interval

level

80%

sides

2-sided

lower limit

0.792

upper limit

1.692

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.72

Confidence interval

level

80%

sides

2-sided

lower limit

0.518

upper limit

0.997

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.8

Confidence interval

level

80%

sides

2-sided

lower limit

0.558

upper limit

1.146

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.65

Confidence interval

level

80%

sides

2-sided

lower limit

0.446

upper limit

0.945

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine albumin to creatinine (UACR) - Part 2 up to Day 180

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine albumin to creatinine (UACR) - Part 2 up to Day 180

End point description

The 24-hour urine collection was started 1 day prior to the clinic visit, after participant urinated for the first time, than all urine was collected for the next 24 hours and refrigerated prior to clinic visit.

End point type

Secondary

End point timeframe

Baseline, Days 30, 90 and 180

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	9	10	19	11	11
Units: Ratio to baseline
geometric mean (confidence interval 80%)	1.04 (0.779 to 1.392)	0.61 (0.454 to 0.808)	0.65 (0.526 to 0.792)	0.69 (0.533 to 0.902)	0.91 (0.696 to 1.200)

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

1.14

Confidence interval

level

80%

sides

2-sided

lower limit

0.765

upper limit

1.699

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.66

Confidence interval

level

80%

sides

2-sided

lower limit

0.446

upper limit

0.984

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.71

Confidence interval

level

80%

sides

2-sided

lower limit

0.501

upper limit

0.995

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.76

Confidence interval

level

80%

sides

2-sided

lower limit

0.52

upper limit

1.107

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Serum Creatine - Parts 1 and 2 at Day 90

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the change from baseline for Serum Creatine - Parts 1 and 2 at Day 90

End point description

Serum creatinine

End point type

Secondary

End point timeframe

Baseline, Days 15, 30 ,60 and 90

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	20	19	22	26	25
Units: umol/L
arithmetic mean (standard error)	-2.55 ± 3.488	-2.60 ± 3.665	0.76 ± 3.555	-3.47 ± 3.043	6.65 ± 3.150

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

-9.2

Confidence interval

level

80%

sides

2-sided

lower limit

-15.253

upper limit

-3.145

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

-9.25

Confidence interval

level

80%

sides

2-sided

lower limit

-15.499

upper limit

-3

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

-5.89

Confidence interval

level

80%

sides

2-sided

lower limit

-12.04

upper limit

0.26

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

-10.12

Confidence interval

level

80%

sides

2-sided

lower limit

-15.763

upper limit

-4.471

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine protein to creatinine (UPCR) from 1st morning void - Parts 1 and 2 at Day 90

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine protein to creatinine (UPCR) from 1st morning void - Parts 1 and 2 at Day 90

End point description

A midstream urine sample was obtained from the first morning void (FMV) on the visit day.

End point type

Secondary

End point timeframe

Baseline, Days 30 and 90

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	20	19	22	26	25
Units: Ratio to baseline
geometric mean (confidence interval 80%)	0.77 (0.69 to 0.86)	0.74 (0.67 to 0.81)	0.71 (0.65 to 0.77)	0.66 (0.58 to 0.76)	0.80 (0.71 to 0.95)

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.99

Confidence interval

level

80%

sides

2-sided

lower limit

0.79

upper limit

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.95

Confidence interval

level

80%

sides

2-sided

lower limit

0.74

upper limit

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.9

Confidence interval

level

80%

sides

2-sided

lower limit

0.71

upper limit

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.81

Confidence interval

level

80%

sides

2-sided

lower limit

0.66

upper limit

1.01

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine protein to creatinine (UPCR) from 1st morning void - Part 2 up to Day 180

Top of page

End point title

Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine protein to creatinine (UPCR) from 1st morning void - Part 2 up to Day 180

End point description

A midstream urine sample was obtained from the first morning void (FMV) on the visit day.

End point type

Secondary

End point timeframe

Baseline, Days 8, 15, 30, 60, 90, 135 and 180

End point values	LNP023 10 mg BID	LNP023 50 mg BID	LNP023 100 mg BID - Part 2	LNP023 200 mg BID	Placebo
Number of subjects analysed	9	10	19	11	11
Units: Ratio to baseline
geometric mean (confidence interval 80%)	0.81 (0.599 to 1.108)	0.72 (0.534 to 0.976)	0.63 (0.507 to 0.784)	0.72 (0.544 to 0.949)	0.79 (0.590 to 1.047)

10 mg vs Placebo

Comparison groups

LNP023 10 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

1.04

Confidence interval

level

80%

sides

2-sided

lower limit

0.68

upper limit

1.579

50 mg vs Placebo

Comparison groups

LNP023 50 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.92

Confidence interval

level

80%

sides

2-sided

lower limit

0.607

upper limit

1.39

100 mg vs Placebo

Comparison groups

LNP023 100 mg BID - Part 2 v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.8

Confidence interval

level

80%

sides

2-sided

lower limit

0.558

upper limit

1.153

200 mg vs Placebo

Comparison groups

LNP023 200 mg BID v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Geometric mean ratio

Point estimate

0.91

Confidence interval

level

80%

sides

2-sided

lower limit

0.614

upper limit

1.362

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment, up to a maximum duration of 197 days.

Adverse event reporting additional description

AE additional description

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

LNP023 10mg

Reporting group description

LNP023 10mg

Reporting group title

LNP023 50mg

Reporting group description

LNP023 50mg

Reporting group title

LNP023 100mg

Reporting group description

LNP023 100mg

Reporting group title

LNP023 200mg

Reporting group description

LNP023 200mg

Reporting group title

Placebo

Reporting group description

Placebo

Serious adverse events	LNP023 10mg	LNP023 50mg	LNP023 100mg	LNP023 200mg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Aspiration
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	LNP023 10mg	LNP023 50mg	LNP023 100mg	LNP023 200mg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	14 / 20 (70.00%)	16 / 19 (84.21%)	15 / 22 (68.18%)	14 / 26 (53.85%)	17 / 25 (68.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Essential thrombocythaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Polycythaemia vera
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Vascular disorders
Hot flush
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	10	0	0	0	0
Hypertension
subjects affected / exposed	1 / 20 (5.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	1	1	1	0	1
Hypotension
subjects affected / exposed	3 / 20 (15.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 26 (7.69%)	0 / 25 (0.00%)
occurrences all number	3	0	0	3	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	1	0	0	0	1
Chest pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Face oedema
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Fatigue
subjects affected / exposed	0 / 20 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)	0 / 26 (0.00%)	3 / 25 (12.00%)
occurrences all number	0	3	1	0	3
Feeling hot
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Influenza like illness
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Oedema
subjects affected / exposed	1 / 20 (5.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	1	0	0	0
Oedema peripheral
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Pain
subjects affected / exposed	2 / 20 (10.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	2	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 20 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	2	1	1	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	1 / 25 (4.00%)
occurrences all number	0	0	0	1	4
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	1	1	0	1
Dyspnoea exertional
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Epistaxis
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 26 (0.00%)	2 / 25 (8.00%)
occurrences all number	2	0	2	0	2
Oropharyngeal pain
subjects affected / exposed	0 / 20 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	2	0	1	0
Rhinitis allergic
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Throat irritation
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	2	0	1	1	0
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Amylase increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Blood creatinine increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Blood potassium increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Blood pressure increased
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	1	0	0	0	1
Blood testosterone decreased
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Blood triglycerides increased
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Coagulation test abnormal
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	1	0	1
Cystatin C increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Lipase increased
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	1 / 25 (4.00%)
occurrences all number	1	0	0	1	1
Pancreatic enzymes increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
SARS-CoV-2 test negative
subjects affected / exposed	1 / 20 (5.00%)	1 / 19 (5.26%)	2 / 22 (9.09%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	2	2	0	0
Weight increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Injury, poisoning and procedural complications
Overdose
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Skin abrasion
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Cardiac disorders
Bundle branch block right
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Palpitations
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Sinus bradycardia
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Supraventricular extrasystoles
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Tachycardia
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Wolff-Parkinson-White syndrome
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Nervous system disorders
Disturbance in attention
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	2	0	0
Dizziness
subjects affected / exposed	2 / 20 (10.00%)	3 / 19 (15.79%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	2	4	1	0	0
Dysaesthesia
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Epilepsy
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Head discomfort
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Headache
subjects affected / exposed	2 / 20 (10.00%)	2 / 19 (10.53%)	2 / 22 (9.09%)	2 / 26 (7.69%)	6 / 25 (24.00%)
occurrences all number	3	2	3	2	7
Migraine
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	4	0	0	0	0
Syncope
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Taste disorder
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Tremor
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	1	0	0	1
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	1	0	0	0	2
Eye disorders
Asthenopia
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 20 (0.00%)	3 / 19 (15.79%)	2 / 22 (9.09%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	4	3	0	0
Abdominal pain
subjects affected / exposed	1 / 20 (5.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	1	1	0	0
Abdominal pain lower
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	3	0	0	0	1
Abdominal pain upper
subjects affected / exposed	2 / 20 (10.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	2	0	0	0	0
Aphthous ulcer
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Diarrhoea
subjects affected / exposed	0 / 20 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)	1 / 26 (3.85%)	3 / 25 (12.00%)
occurrences all number	0	3	1	1	3
Dyspepsia
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Epigastric discomfort
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Food poisoning
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Mouth haemorrhage
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Mouth ulceration
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Nausea
subjects affected / exposed	3 / 20 (15.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	7	1	0	0	2
Toothache
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	1	1	0
Vomiting
subjects affected / exposed	3 / 20 (15.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)	1 / 26 (3.85%)	1 / 25 (4.00%)
occurrences all number	3	2	0	1	1
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Alopecia
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Dermatosis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Dry skin
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Eczema
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Eczema nummular
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Erythema
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	2	0	0	0	0
Pruritus
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Rash
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	2	0	0	0
Vasculitic rash
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Haematuria
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Renal pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Renal vasculitis
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 20 (10.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	2	0	3	0	0
Back pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	3 / 22 (13.64%)	1 / 26 (3.85%)	3 / 25 (12.00%)
occurrences all number	1	0	3	2	3
Bursitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Flank pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Joint swelling
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Muscle spasms
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	2	0	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Pain in extremity
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Plantar fasciitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Polyarthritis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Infections and infestations
Asymptomatic bacteriuria
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	1	0	1
Bronchitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
COVID-19
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	1	0	0	0	1
Conjunctivitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Gastroenteritis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	2	0	1
Gingivitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	1 / 25 (4.00%)
occurrences all number	0	0	0	1	1
Hordeolum
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Influenza
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Nasopharyngitis
subjects affected / exposed	2 / 20 (10.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)	1 / 26 (3.85%)	2 / 25 (8.00%)
occurrences all number	2	3	0	1	3
Norovirus infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Onychomycosis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Oral herpes
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Otitis externa
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Otitis media
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Pharyngitis
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Tonsillitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Tooth abscess
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Tracheobronchitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	1	0	0	1	0
Urinary tract infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	0	0	1
Viral infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Diabetes mellitus
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Gout
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	1	0	1	0
Hypercholesterolaemia
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	1 / 25 (4.00%)
occurrences all number	0	0	0	1	1
Hypermagnesaemia
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Hyponatraemia
subjects affected / exposed	0 / 20 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	1	0	0	0
Hypophosphataemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 26 (3.85%)	0 / 25 (0.00%)
occurrences all number	0	0	0	1	0
Iron deficiency
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0
Metabolic acidosis
subjects affected / exposed	0 / 20 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	0	0	1	0	0
Vitamin B12 deficiency
subjects affected / exposed	1 / 20 (5.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 26 (0.00%)	0 / 25 (0.00%)
occurrences all number	1	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

31 Mar 2018

The purpose of this amendment was to include patients with a pulse rate <50 if the patient was otherwise in a physically good and stable condition without any other significant ECG abnormalities as judged by t.he investigator. The study stopping rules were adapted based on feedback by HA. Assessment schedule was updated for endocrine parameters to be checked on Day 15 and 30, additional pregnancy test on Day 90 for participating patients of child bearing potential.

30 Sep 2018

Amendment included changes to: number of 24h urine collections were reduced, inclusion criteria was modified: the urine protein level required was decreased from ≥1g/24h to ≥0.75g/24h from a 24h urine collection, or a urine protein to creatinine ratio (UPCR) ≥0.8g/g (90mg/mmol) from FMV sample, PK sampling, and PD and exploratory biomarkers were removed from Day 1 in the assessment schedule;

31 May 2019

The main purpose of this amendment was to increase the duration of treatment phase from 90 days to 180 days in Part 2 of the trial in order to gather information about longer term treatment effects and safety information for LNP023. In addition, the description and implementation of the planned adaptations to Part 2 of the trial was further clarified/modified.

30 Apr 2020

The main purpose of this amendment was to confirm the final number of patients to be recruited into Part 2 of the study and the doses to be investigated based on the results of the Part 1 interim analysis (IA1).

30 Sep 2020

The purpose of this amendment was to update the unblinding plan for the study. The update to this plan allowed sharing of unblinded group level results from IA1 and IA2 to support initiation of phase 3 IgAN study

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: An adaptive seamless randomized, double-blind, placebo-controlled, dose ranging study to investigate the efficacy and safety of LNP023 in primary IgA nephropathy patients

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: MCP-Mod estimates of the ratio to baseline of urine protein to creatinine ratio (UPCR) (g/mol) - Parts 1 and 2 at Day 90

Primary: MCP-Mod estimates of the ratio to baseline of urine protein to creatinine ratio (UPCR) (g/mol) - Parts 1 and 2 at Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90

Secondary: Shift table from baseline for Hematuria levels - Parts 1 and 2 at Day 90

Secondary: Shift table from baseline for Hematuria levels - Parts 1 and 2 at Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24hour urine protein (UP) - Parts 1 and 2 to Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24hour urine protein (UP) - Parts 1 and 2 to Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline of 24 hour urine albumin (UA) - Parts 1 and 2 to Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline of 24 hour urine albumin (UA) - Parts 1 and 2 to Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine albumin to creatinine (UACR) - Parts 1 and 2 to Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine albumin to creatinine (UACR) - Parts 1 and 2 to Day 90

Secondary: Plasma Pharmacokinetics (PK) of Area Under the Curve at steady state (AUCtau,ss and AUClast,ss) at Day 30

Secondary: Plasma Pharmacokinetics (PK) of Area Under the Curve at steady state (AUCtau,ss and AUClast,ss) at Day 30

Secondary: Plasma Pharmacokinetics (PK) of pre-dose trough at steady state (Ctrough,ss) and maximum concentrations (Cmax,ss) at Day 30

Secondary: Plasma Pharmacokinetics (PK) of pre-dose trough at steady state (Ctrough,ss) and maximum concentrations (Cmax,ss) at Day 30

Secondary: Plasma Pharmacokinetics (PK) of time to maximum concentration at steady state (Tmax,ss) at Day 30

Secondary: Plasma Pharmacokinetics (PK) of time to maximum concentration at steady state (Tmax,ss) at Day 30

Secondary: Amount of LNP023 excreted into urine (Ae,ss) at Day 30

Secondary: Amount of LNP023 excreted into urine (Ae,ss) at Day 30

Secondary: Percent of LNP023 excreted into urine at Day 30

Secondary: Percent of LNP023 excreted into urine at Day 30

Secondary: Renal clearance from plasma at steady state (CLr,ss) at Day 30

Secondary: Renal clearance from plasma at steady state (CLr,ss) at Day 30

Secondary: Change from baseline in plasma levels of circulating fragment of Factor B (Bb) and soluble terminal complement complex (sC5b-9) biomarkers for Parts 1 and 2 to Day 90

Secondary: Change from baseline in plasma levels of circulating fragment of Factor B (Bb) and soluble terminal complement complex (sC5b-9) biomarkers for Parts 1 and 2 to Day 90

Secondary: Estimation of lowest dose providing maximal reduction of proteinuria

Secondary: Estimation of lowest dose providing maximal reduction of proteinuria

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180

Secondary: Shift table from baseline for Hematuria levels - Part 2 at Day 180

Secondary: Shift table from baseline for Hematuria levels - Part 2 at Day 180

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline in protein level urine using the urine protein-creatinine ratio (UPCR) from 24 hour urine collection - Part 2 up to Day 180

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline in protein level urine using the urine protein-creatinine ratio (UPCR) from 24 hour urine collection - Part 2 up to Day 180

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine albumin to creatinine (UACR) - Part 2 up to Day 180

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine albumin to creatinine (UACR) - Part 2 up to Day 180

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Serum Creatine - Parts 1 and 2 at Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the change from baseline for Serum Creatine - Parts 1 and 2 at Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine protein to creatinine (UPCR) from 1st morning void - Parts 1 and 2 at Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine protein to creatinine (UPCR) from 1st morning void - Parts 1 and 2 at Day 90

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine protein to creatinine (UPCR) from 1st morning void - Part 2 up to Day 180

Secondary: Mixed Model of Repeated Measures (MMRM) of the ratio to baseline in 24 hour urine protein to creatinine (UPCR) from 1st morning void - Part 2 up to Day 180

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An adaptive seamless randomized, double-blind, placebo-controlled, dose ranging study to investigate the efficacy and safety of LNP023 in primary IgA nephropathy patients