Trial Outcomes & Findings for Study of Safety, Efficacy, Tolerability, Pharmacokinetics and Pharmacodynamics of LNP023 in in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) (NCT NCT03439839)

Last Updated: 2024-06-12

Results Overview

Serum LDH was used as an intravascular hemolysis marker to assess the effect of iptacopan on the reduction of chronic hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) patients when administered in addition to SoC (monoclonal antibody with anti C5 activity) Baseline is defined as the mean of the last 3 measurements prior to dose administration.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Baseline and Day 92

Results posted on

2024-06-12

Participant Flow

Participants took part in 3 investigative sites in 3 countries: France (1), Italy (1) and Germany (1).

All patients needed to complete vaccinations against N. meningitidis, S. pneumoniae and H. influenzae at least 4 weeks prior to starting LNP023 treatment. If LNP023 treatment had to start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment was initiated. Prior to treatment, both cohorts underwent a screening period of up to 68 days followed by a baseline visit.

Participant milestones

Participant milestones
Measure	Cohort 1: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.
Overall Study STARTED	10	6
Overall Study COMPLETED	7	6
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.
Overall Study Death	3	0

Baseline Characteristics

Study of Safety, Efficacy, Tolerability, Pharmacokinetics and Pharmacodynamics of LNP023 in in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	44.4 years STANDARD_DEVIATION 15.57 • n=5 Participants	51.7 years STANDARD_DEVIATION 9.83 • n=7 Participants	47.1 years STANDARD_DEVIATION 13.82 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 92

Population: The Pharmacodynamic (PD) analysis set is defined as patients with available PD data and no protocol deviations with relevant impact on PD data. The overall number of participants analyzed represents the participants in the PD analysis set who had valid measurements of LDH at Baseline and Day 92.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=9 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=5 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total n=14 Participants Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Percent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92	-53.59 Percent change from Baseline Interval -61.38 to -45.79	-25.56 Percent change from Baseline Interval -46.92 to -4.2	-43.58 Percent change from Baseline Interval -53.57 to -33.58	—

SECONDARY outcome

Timeframe: Baseline, day 8, 15, 29, 57 and 92

Population: The overall number of participants analyzed represents the participants in the PD analysis set. The number analyzed per row represents the participants with a valid LDH value at both baseline and that particular visit

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total n=16 Participants Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level Day 8	-272.57 U/L Interval -349.07 to -196.07	-145.22 U/L Interval -196.3 to -94.15	-224.81 U/L Interval -279.88 to -169.74	—
Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level Day 15	-353.97 U/L Interval -486.36 to -221.57	-175.07 U/L Interval -247.55 to -102.59	-294.33 U/L Interval -388.42 to -200.24	—
Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level Day 29	-368.17 U/L Interval -510.15 to -226.18	-191.22 U/L Interval -258.88 to -123.56	-301.81 U/L Interval -395.89 to -207.73	—
Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level Day 57	-317.07 U/L Interval -459.11 to -175.03	-135.89 U/L Interval -212.28 to -59.5	-249.13 U/L Interval -344.24 to -154.01	—
Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level Day 92	-330.52 U/L Interval -488.02 to -173.01	-109.07 U/L Interval -196.69 to -21.45	-251.43 U/L Interval -361.88 to -140.98	—

SECONDARY outcome

Timeframe: Baseline; day 1, 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 92, 113, 127, 141, 155, 169, 197, 225, 253, 281, 309, 337, 393, 449, 505, 561, 617, 673, 729, 785, 841, 897, 953, 1009, 1065, 1121, 1177, 1233

Population: The overall number of participants analyzed represents the participants in the PD analysis set. The number analyzed per row represents the participants with a valid hemoglobin value at both baseline and that particular visit.

Hemoglobin was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Absolute Change From Baseline in Hemoglobin Day 673	38.42 g/L Standard Deviation 13.407	38.13 g/L Standard Deviation 15.418	—	—
Absolute Change From Baseline in Hemoglobin Day 1	-4.05 g/L Standard Deviation 8.750	-6.67 g/L Standard Deviation 7.218	—	—
Absolute Change From Baseline in Hemoglobin Day 2	-3.65 g/L Standard Deviation 7.638	-8.06 g/L Standard Deviation 6.830	—	—
Absolute Change From Baseline in Hemoglobin Day 8	12.85 g/L Standard Deviation 9.228	20.11 g/L Standard Deviation 13.475	—	—
Absolute Change From Baseline in Hemoglobin Day 15	20.25 g/L Standard Deviation 10.122	26.44 g/L Standard Deviation 10.047	—	—
Absolute Change From Baseline in Hemoglobin Day 22	24.15 g/L Standard Deviation 11.898	35.11 g/L Standard Deviation 11.065	—	—
Absolute Change From Baseline in Hemoglobin Day 29	28.25 g/L Standard Deviation 13.131	35.11 g/L Standard Deviation 10.141	—	—
Absolute Change From Baseline in Hemoglobin Day 36	29.55 g/L Standard Deviation 12.166	33.94 g/L Standard Deviation 10.062	—	—
Absolute Change From Baseline in Hemoglobin Day 43	26.15 g/L Standard Deviation 12.571	31.11 g/L Standard Deviation 7.428	—	—
Absolute Change From Baseline in Hemoglobin Day 57	27.05 g/L Standard Deviation 10.855	35.94 g/L Standard Deviation 10.804	—	—
Absolute Change From Baseline in Hemoglobin Day 71	24.53 g/L Standard Deviation 12.259	28.54 g/L Standard Deviation 8.080	—	—
Absolute Change From Baseline in Hemoglobin Day 85	28.65 g/L Standard Deviation 15.722	30.72 g/L Standard Deviation 15.008	—	—
Absolute Change From Baseline in Hemoglobin Day 92	31.85 g/L Standard Deviation 14.543	32.43 g/L Standard Deviation 14.584	—	—
Absolute Change From Baseline in Hemoglobin Day 113	30.14 g/L Standard Deviation 14.831	32.43 g/L Standard Deviation 11.092	—	—
Absolute Change From Baseline in Hemoglobin Day 127	33.92 g/L Standard Deviation 16.882	38.92 g/L Standard Deviation 13.519	—	—
Absolute Change From Baseline in Hemoglobin Day 141	28.05 g/L Standard Deviation 17.088	37.23 g/L Standard Deviation 15.802	—	—
Absolute Change From Baseline in Hemoglobin Day 155	28.28 g/L Standard Deviation 17.370	37.83 g/L Standard Deviation 12.287	—	—
Absolute Change From Baseline in Hemoglobin Day 169	27.05 g/L Standard Deviation 17.253	39.43 g/L Standard Deviation 11.174	—	—
Absolute Change From Baseline in Hemoglobin Day 197	28.95 g/L Standard Deviation 15.429	31.89 g/L Standard Deviation 16.385	—	—
Absolute Change From Baseline in Hemoglobin Day 225	28.65 g/L Standard Deviation 17.258	28.67 g/L Standard Deviation 7.147	—	—
Absolute Change From Baseline in Hemoglobin Day 253	26.95 g/L Standard Deviation 18.015	28.17 g/L Standard Deviation 12.039	—	—
Absolute Change From Baseline in Hemoglobin Day 281	29.91 g/L Standard Deviation 18.351	45.54 g/L Standard Deviation 16.168	—	—
Absolute Change From Baseline in Hemoglobin Day 309	27.17 g/L Standard Deviation 15.152	36.29 g/L Standard Deviation 9.866	—	—
Absolute Change From Baseline in Hemoglobin Day 337	26.28 g/L Standard Deviation 16.733	32.50 g/L Standard Deviation 10.700	—	—
Absolute Change From Baseline in Hemoglobin Day 393	28.47 g/L Standard Deviation 18.801	39.79 g/L Standard Deviation 12.930	—	—
Absolute Change From Baseline in Hemoglobin Day 449	31.22 g/L Standard Deviation 18.573	37.93 g/L Standard Deviation 10.547	—	—
Absolute Change From Baseline in Hemoglobin Day 505	24.89 g/L Standard Deviation 13.435	44.28 g/L Standard Deviation 18.271	—	—
Absolute Change From Baseline in Hemoglobin Day 561	29.25 g/L Standard Deviation 18.665	40.13 g/L Standard Deviation 11.653	—	—
Absolute Change From Baseline in Hemoglobin Day 617	32.23 g/L Standard Deviation 18.335	42.78 g/L Standard Deviation 17.771	—	—
Absolute Change From Baseline in Hemoglobin Day 729	31.28 g/L Standard Deviation 15.366	34.92 g/L Standard Deviation 11.357	—	—
Absolute Change From Baseline in Hemoglobin Day 785	11.63 g/L Standard Deviation 22.691	40.04 g/L Standard Deviation 26.752	—	—
Absolute Change From Baseline in Hemoglobin Day 841	24.27 g/L Standard Deviation 18.109	38.54 g/L Standard Deviation 23.649	—	—
Absolute Change From Baseline in Hemoglobin Day 897	31.85 g/L Standard Deviation 17.303	56.83 g/L Standard Deviation 20.035	—	—
Absolute Change From Baseline in Hemoglobin Day 953	23.93 g/L Standard Deviation 14.964	—	—	—
Absolute Change From Baseline in Hemoglobin Day 1009	23.99 g/L Standard Deviation 19.396	—	—	—
Absolute Change From Baseline in Hemoglobin Day 1065	29.07 g/L Standard Deviation 17.334	—	—	—
Absolute Change From Baseline in Hemoglobin Day 1121	27.27 g/L Standard Deviation 14.536	—	—	—
Absolute Change From Baseline in Hemoglobin Day 1177	32.28 g/L Standard Deviation 11.180	—	—	—
Absolute Change From Baseline in Hemoglobin Day 1233	33.08 g/L Standard Deviation 10.196	—	—	—

SECONDARY outcome

Population: The overall number of participants analyzed represents the participants in the PD analysis set. The number analyzed per row represents the participants with a valid free hemoglobin value at both baseline and that particular visit.

Free hemoglobin was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Absolute Change From Baseline in Free Hemoglobin Day 1	15.26 mg/dL Standard Deviation 36.879	9.16 mg/dL Standard Deviation 15.310	—	—
Absolute Change From Baseline in Free Hemoglobin Day 2	-26.73 mg/dL Standard Deviation 40.706	-3.94 mg/dL Standard Deviation 6.785	—	—
Absolute Change From Baseline in Free Hemoglobin Day 8	-24.03 mg/dL Standard Deviation 43.102	-2.04 mg/dL Standard Deviation 6.725	—	—
Absolute Change From Baseline in Free Hemoglobin Day 15	-23.16 mg/dL Standard Deviation 41.190	14.21 mg/dL Standard Deviation 43.762	—	—
Absolute Change From Baseline in Free Hemoglobin Day 22	-22.90 mg/dL Standard Deviation 39.726	-0.66 mg/dL Standard Deviation 6.960	—	—
Absolute Change From Baseline in Free Hemoglobin Day 29	-20.03 mg/dL Standard Deviation 42.349	-1.21 mg/dL Standard Deviation 8.108	—	—
Absolute Change From Baseline in Free Hemoglobin Day 36	-12.42 mg/dL Standard Deviation 47.495	-2.56 mg/dL Standard Deviation 6.914	—	—
Absolute Change From Baseline in Free Hemoglobin Day 43	-13.63 mg/dL Standard Deviation 24.961	-0.54 mg/dL Standard Deviation 6.546	—	—
Absolute Change From Baseline in Free Hemoglobin Day 57	1.71 mg/dL Standard Deviation 14.138	-1.84 mg/dL Standard Deviation 6.662	—	—
Absolute Change From Baseline in Free Hemoglobin Day 71	-17.92 mg/dL Standard Deviation 34.378	0.18 mg/dL Standard Deviation 1.466	—	—
Absolute Change From Baseline in Free Hemoglobin Day 85	-16.80 mg/dL Standard Deviation 47.407	1.90 mg/dL Standard Deviation 2.338	—	—
Absolute Change From Baseline in Free Hemoglobin Day 92	-25.12 mg/dL Standard Deviation 42.237	-3.31 mg/dL Standard Deviation 6.295	—	—
Absolute Change From Baseline in Free Hemoglobin Day 113	-24.00 mg/dL Standard Deviation 41.084	16.09 mg/dL Standard Deviation 42.454	—	—
Absolute Change From Baseline in Free Hemoglobin Day 127	-18.07 mg/dL Standard Deviation 52.791	1.42 mg/dL Standard Deviation 2.945	—	—
Absolute Change From Baseline in Free Hemoglobin Day 141	-24.03 mg/dL Standard Deviation 40.625	-1.52 mg/dL Standard Deviation 8.137	—	—
Absolute Change From Baseline in Free Hemoglobin Day 155	-20.58 mg/dL Standard Deviation 43.690	-2.43 mg/dL Standard Deviation 8.741	—	—
Absolute Change From Baseline in Free Hemoglobin Day 169	-1.00 mg/dL Standard Deviation 91.222	10.24 mg/dL Standard Deviation 19.275	—	—
Absolute Change From Baseline in Free Hemoglobin Day 197	14.93 mg/dL Standard Deviation 105.958	3.19 mg/dL Standard Deviation 5.185	—	—
Absolute Change From Baseline in Free Hemoglobin Day 225	10.64 mg/dL Standard Deviation 101.866	15.89 mg/dL Standard Deviation 32.159	—	—
Absolute Change From Baseline in Free Hemoglobin Day 253	-21.97 mg/dL Standard Deviation 40.320	34.84 mg/dL Standard Deviation 61.838	—	—
Absolute Change From Baseline in Free Hemoglobin Day 281	-24.19 mg/dL Standard Deviation 39.910	-1.36 mg/dL Standard Deviation 7.326	—	—
Absolute Change From Baseline in Free Hemoglobin Day 309	-21.57 mg/dL Standard Deviation 42.638	-2.26 mg/dL Standard Deviation 9.656	—	—
Absolute Change From Baseline in Free Hemoglobin Day 337	-20.69 mg/dL Standard Deviation 42.592	31.39 mg/dL Standard Deviation 55.947	—	—
Absolute Change From Baseline in Free Hemoglobin Day 393	-17.29 mg/dL Standard Deviation 42.263	-2.11 mg/dL Standard Deviation 8.297	—	—
Absolute Change From Baseline in Free Hemoglobin Day 449	-28.60 mg/dL Standard Deviation 44.210	-3.93 mg/dL Standard Deviation 7.781	—	—
Absolute Change From Baseline in Free Hemoglobin Day 505	-33.24 mg/dL Standard Deviation 41.787	-1.69 mg/dL Standard Deviation 6.335	—	—
Absolute Change From Baseline in Free Hemoglobin Day 561	-34.25 mg/dL Standard Deviation 43.692	1.59 mg/dL Standard Deviation 2.372	—	—
Absolute Change From Baseline in Free Hemoglobin Day 617	-34.68 mg/dL Standard Deviation 44.127	-0.22 mg/dL Standard Deviation 6.960	—	—
Absolute Change From Baseline in Free Hemoglobin Day 673	-37.43 mg/dL Standard Deviation 54.005	2.39 mg/dL Standard Deviation 15.832	—	—
Absolute Change From Baseline in Free Hemoglobin Day 729	-28.88 mg/dL Standard Deviation 38.550	-3.99 mg/dL Standard Deviation 7.294	—	—
Absolute Change From Baseline in Free Hemoglobin Day 785	-2.55 mg/dL Standard Deviation 4.388	-0.67 mg/dL Standard Deviation 3.206	—	—
Absolute Change From Baseline in Free Hemoglobin Day 841	-33.12 mg/dL Standard Deviation 43.462	1.60 mg/dL Standard Deviation 4.485	—	—
Absolute Change From Baseline in Free Hemoglobin Day 897	-12.98 mg/dL Standard Deviation 22.233	4.77 mg/dL Standard Deviation 5.468	—	—
Absolute Change From Baseline in Free Hemoglobin Day 953	-34.41 mg/dL Standard Deviation 46.196	—	—	—
Absolute Change From Baseline in Free Hemoglobin Day 1009	8.39 mg/dL Standard Deviation 135.082	—	—	—
Absolute Change From Baseline in Free Hemoglobin Day 1065	-34.10 mg/dL Standard Deviation 44.867	—	—	—
Absolute Change From Baseline in Free Hemoglobin Day 1121	-33.45 mg/dL Standard Deviation 43.628	—	—	—
Absolute Change From Baseline in Free Hemoglobin Day 1177	-16.30 mg/dL Standard Deviation 23.441	—	—	—
Absolute Change From Baseline in Free Hemoglobin Day 1233	-12.27 mg/dL Standard Deviation 20.734	—	—	—

SECONDARY outcome

Population: The overall number of participants analyzed represents the participants in the PD analysis set. The number analyzed per row represents the participants with a valid reticulocyte count value both at baseline and that particular visit

Reticulocytes count was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Absolute Change From Baseline in Reticulocytes Count Day 1	4.44 10^9 cells/L Standard Deviation 33.269	1.62 10^9 cells/L Standard Deviation 22.790	—	—
Absolute Change From Baseline in Reticulocytes Count Day 2	8.61 10^9 cells/L Standard Deviation 52.306	4.39 10^9 cells/L Standard Deviation 31.658	—	—
Absolute Change From Baseline in Reticulocytes Count Day 8	-96.94 10^9 cells/L Standard Deviation 69.179	-104.55 10^9 cells/L Standard Deviation 88.085	—	—
Absolute Change From Baseline in Reticulocytes Count Day 15	-130.15 10^9 cells/L Standard Deviation 80.335	-130.40 10^9 cells/L Standard Deviation 107.295	—	—
Absolute Change From Baseline in Reticulocytes Count Day 22	-139.26 10^9 cells/L Standard Deviation 78.206	-147.70 10^9 cells/L Standard Deviation 99.438	—	—
Absolute Change From Baseline in Reticulocytes Count Day 29	-132.28 10^9 cells/L Standard Deviation 76.822	-169.68 10^9 cells/L Standard Deviation 129.743	—	—
Absolute Change From Baseline in Reticulocytes Count Day 36	-130.73 10^9 cells/L Standard Deviation 72.017	-167.51 10^9 cells/L Standard Deviation 137.214	—	—
Absolute Change From Baseline in Reticulocytes Count Day 43	-129.02 10^9 cells/L Standard Deviation 64.301	-160.05 10^9 cells/L Standard Deviation 132.859	—	—
Absolute Change From Baseline in Reticulocytes Count Day 57	-117.69 10^9 cells/L Standard Deviation 65.394	-149.53 10^9 cells/L Standard Deviation 116.803	—	—
Absolute Change From Baseline in Reticulocytes Count Day 71	-106.83 10^9 cells/L Standard Deviation 62.973	-146.87 10^9 cells/L Standard Deviation 129.217	—	—
Absolute Change From Baseline in Reticulocytes Count Day 85	-113.96 10^9 cells/L Standard Deviation 65.278	-167.16 10^9 cells/L Standard Deviation 156.013	—	—
Absolute Change From Baseline in Reticulocytes Count Day 92	-110.54 10^9 cells/L Standard Deviation 62.638	-150.02 10^9 cells/L Standard Deviation 105.893	—	—
Absolute Change From Baseline in Reticulocytes Count Day 113	-96.78 10^9 cells/L Standard Deviation 66.366	-147.06 10^9 cells/L Standard Deviation 129.118	—	—
Absolute Change From Baseline in Reticulocytes Count Day 127	-107.84 10^9 cells/L Standard Deviation 57.904	-149.92 10^9 cells/L Standard Deviation 115.401	—	—
Absolute Change From Baseline in Reticulocytes Count Day 141	-115.17 10^9 cells/L Standard Deviation 70.942	-108.39 10^9 cells/L Standard Deviation 54.412	—	—
Absolute Change From Baseline in Reticulocytes Count Day 155	-99.90 10^9 cells/L Standard Deviation 62.273	-98.67 10^9 cells/L Standard Deviation 65.700	—	—
Absolute Change From Baseline in Reticulocytes Count Day 169	-109.39 10^9 cells/L Standard Deviation 63.159	-84.57 10^9 cells/L Standard Deviation 64.082	—	—
Absolute Change From Baseline in Reticulocytes Count Day 197	-98.87 10^9 cells/L Standard Deviation 85.280	-152.09 10^9 cells/L Standard Deviation 137.856	—	—
Absolute Change From Baseline in Reticulocytes Count Day 225	-104.11 10^9 cells/L Standard Deviation 72.206	-143.68 10^9 cells/L Standard Deviation 149.716	—	—
Absolute Change From Baseline in Reticulocytes Count Day 253	-104.30 10^9 cells/L Standard Deviation 64.401	-139.05 10^9 cells/L Standard Deviation 127.212	—	—
Absolute Change From Baseline in Reticulocytes Count Day 281	-111.11 10^9 cells/L Standard Deviation 60.896	-121.06 10^9 cells/L Standard Deviation 66.564	—	—
Absolute Change From Baseline in Reticulocytes Count Day 309	-116.88 10^9 cells/L Standard Deviation 51.145	-114.06 10^9 cells/L Standard Deviation 77.982	—	—
Absolute Change From Baseline in Reticulocytes Count Day 337	-113.31 10^9 cells/L Standard Deviation 61.144	-170.89 10^9 cells/L Standard Deviation 142.577	—	—
Absolute Change From Baseline in Reticulocytes Count Day 393	-58.54 10^9 cells/L Standard Deviation 152.003	-183.20 10^9 cells/L Standard Deviation 122.298	—	—
Absolute Change From Baseline in Reticulocytes Count Day 449	-89.44 10^9 cells/L Standard Deviation 77.782	-152.66 10^9 cells/L Standard Deviation 124.244	—	—
Absolute Change From Baseline in Reticulocytes Count Day 505	-100.68 10^9 cells/L Standard Deviation 64.132	-135.80 10^9 cells/L Standard Deviation 117.488	—	—
Absolute Change From Baseline in Reticulocytes Count Day 561	-101.63 10^9 cells/L Standard Deviation 67.525	-163.34 10^9 cells/L Standard Deviation 121.860	—	—
Absolute Change From Baseline in Reticulocytes Count Day 617	-101.73 10^9 cells/L Standard Deviation 54.916	-132.40 10^9 cells/L Standard Deviation 122.940	—	—
Absolute Change From Baseline in Reticulocytes Count Day 673	-137.05 10^9 cells/L Standard Deviation 63.373	-150.14 10^9 cells/L Standard Deviation 130.898	—	—
Absolute Change From Baseline in Reticulocytes Count Day 729	-101.16 10^9 cells/L Standard Deviation 63.442	-179.15 10^9 cells/L Standard Deviation 131.007	—	—
Absolute Change From Baseline in Reticulocytes Count Day 785	-56.22 10^9 cells/L Standard Deviation 26.739	-134.60 10^9 cells/L Standard Deviation 141.947	—	—
Absolute Change From Baseline in Reticulocytes Count Day 841	-103.96 10^9 cells/L Standard Deviation 60.469	-145.80 10^9 cells/L Standard Deviation 140.363	—	—
Absolute Change From Baseline in Reticulocytes Count Day 897	-111.41 10^9 cells/L Standard Deviation 58.641	-81.27 10^9 cells/L Standard Deviation 36.298	—	—
Absolute Change From Baseline in Reticulocytes Count Day 953	-91.00 10^9 cells/L Standard Deviation 52.203	—	—	—
Absolute Change From Baseline in Reticulocytes Count Day 1009	-110.33 10^9 cells/L Standard Deviation 61.354	—	—	—
Absolute Change From Baseline in Reticulocytes Count Day 1065	-127.35 10^9 cells/L Standard Deviation 61.501	—	—	—
Absolute Change From Baseline in Reticulocytes Count Day 1121	-115.96 10^9 cells/L Standard Deviation 55.981	—	—	—
Absolute Change From Baseline in Reticulocytes Count Day 1177	-140.14 10^9 cells/L Standard Deviation 73.898	—	—	—
Absolute Change From Baseline in Reticulocytes Count Day 1233	-123.40 10^9 cells/L Standard Deviation 70.558	—	—	—

SECONDARY outcome

Timeframe: Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233

Population: The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of C3 fragment deposition. The number analyzed per row represents the participants with a valid C3 fragment deposition value both at baseline and that particular visit

C3 fragment deposition on PNH Red blood cell (RBC) was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as Day 1 pre-dose measurement.

Outcome measures

SECONDARY outcome

Timeframe: Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233

Mean PNH clone size on Red Blood Cells (RBC) was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.

Outcome measures

SECONDARY outcome

Timeframe: Day 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 92, 113, 127, 141, 155, 169, 197, 225, 253, 281, 309, 337, 393, 449, 505, 561, 617, 673, 729, 785, 841, 897, 953, 1009, 1065, 1121, 1177, 1233

Haptoglobin level was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=9 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=4 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Mean Haptoglobin Levels Day 2	0.55 g/L Standard Deviation 0.071	0.30 g/L Standard Deviation 0.141	—	—
Mean Haptoglobin Levels Day 8	0.70 g/L Standard Deviation 0.548	0.77 g/L Standard Deviation 0.306	—	—
Mean Haptoglobin Levels Day 15	0.93 g/L Standard Deviation 0.960	0.60 g/L Standard Deviation 0.141	—	—
Mean Haptoglobin Levels Day 22	1.18 g/L Standard Deviation 1.387	0.70 g/L Standard Deviation 0.483	—	—
Mean Haptoglobin Levels Day 29	0.94 g/L Standard Deviation 0.896	0.83 g/L Standard Deviation 0.586	—	—
Mean Haptoglobin Levels Day 36	1.08 g/L Standard Deviation 0.779	0.97 g/L Standard Deviation 0.503	—	—
Mean Haptoglobin Levels Day 43	1.26 g/L Standard Deviation 1.401	0.70 g/L Standard Deviation 0.520	—	—
Mean Haptoglobin Levels Day 57	0.63 g/L Standard Deviation 0.416	1.20 g/L	—	—
Mean Haptoglobin Levels Day 71	0.75 g/L Standard Deviation 0.473	0.80 g/L	—	—
Mean Haptoglobin Levels Day 85	0.87 g/L Standard Deviation 0.611	—	—	—
Mean Haptoglobin Levels Day 92	0.95 g/L Standard Deviation 0.495	0.80 g/L	—	—
Mean Haptoglobin Levels Day 113	0.63 g/L Standard Deviation 0.493	0.50 g/L	—	—
Mean Haptoglobin Levels Day 127	0.47 g/L Standard Deviation 0.208	—	—	—
Mean Haptoglobin Levels Day 141	0.57 g/L Standard Deviation 0.306	0.70 g/L	—	—
Mean Haptoglobin Levels Day 155	0.50 g/L	0.80 g/L	—	—
Mean Haptoglobin Levels Day 169	0.63 g/L Standard Deviation 0.577	0.50 g/L	—	—
Mean Haptoglobin Levels Day 197	0.80 g/L Standard Deviation 0.700	—	—	—
Mean Haptoglobin Levels Day 225	0.65 g/L Standard Deviation 0.705	—	—	—
Mean Haptoglobin Levels Day 253	0.63 g/L Standard Deviation 0.519	—	—	—
Mean Haptoglobin Levels Day 281	0.50 g/L Standard Deviation 0.283	0.30 g/L	—	—
Mean Haptoglobin Levels Day 309	0.75 g/L Standard Deviation 0.071	0.50 g/L	—	—
Mean Haptoglobin Levels Day 337	0.40 g/L	—	—	—
Mean Haptoglobin Levels Day 393	0.60 g/L Standard Deviation 0.283	—	—	—
Mean Haptoglobin Levels Day 449	0.20 g/L	0.60 g/L	—	—
Mean Haptoglobin Levels Day 505	0.60 g/L Standard Deviation 0.141	0.60 g/L	—	—
Mean Haptoglobin Levels Day 561	0.60 g/L	0.70 g/L	—	—
Mean Haptoglobin Levels Day 617	0.30 g/L Standard Deviation 0.141	1.90 g/L Standard Deviation 1.838	—	—
Mean Haptoglobin Levels Day 673	0.30 g/L	0.70 g/L	—	—
Mean Haptoglobin Levels Day 729	0.35 g/L Standard Deviation 0.071	0.50 g/L	—	—
Mean Haptoglobin Levels Day 785	1.00 g/L	1.25 g/L Standard Deviation 0.919	—	—
Mean Haptoglobin Levels Day 841	0.47 g/L Standard Deviation 0.153	0.85 g/L Standard Deviation 0.212	—	—
Mean Haptoglobin Levels Day 897	0.33 g/L Standard Deviation 0.058	—	—	—
Mean Haptoglobin Levels Day 953	0.50 g/L Standard Deviation 0.141	—	—	—
Mean Haptoglobin Levels Day 1009	0.45 g/L Standard Deviation 0.071	—	—	—
Mean Haptoglobin Levels Day 1065	2.05 g/L Standard Deviation 1.768	—	—	—
Mean Haptoglobin Levels Day 1121	1.00 g/L Standard Deviation 0.935	—	—	—
Mean Haptoglobin Levels Day 1177	0.40 g/L Standard Deviation 0.000	—	—	—
Mean Haptoglobin Levels Day 1233	0.95 g/L Standard Deviation 0.636	—	—	—

SECONDARY outcome

Population: The overall number of participants analyzed represents the participants in the PD analysis set. The number analyzed per row represents the participants with a valid bilirubin value both at baseline and that particular visit.

Bilirubin was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Absolute Change From Baseline in Total Bilirubin Day 1	2.94 umol/L Standard Deviation 13.038	1.36 umol/L Standard Deviation 4.978	—	—
Absolute Change From Baseline in Total Bilirubin Day 2	-21.06 umol/L Standard Deviation 15.647	-25.47 umol/L Standard Deviation 21.598	—	—
Absolute Change From Baseline in Total Bilirubin Day 8	-23.66 umol/L Standard Deviation 16.081	-25.97 umol/L Standard Deviation 24.380	—	—
Absolute Change From Baseline in Total Bilirubin Day 15	-23.86 umol/L Standard Deviation 16.538	-26.97 umol/L Standard Deviation 24.043	—	—
Absolute Change From Baseline in Total Bilirubin Day 22	-25.36 umol/L Standard Deviation 15.403	-25.14 umol/L Standard Deviation 23.541	—	—
Absolute Change From Baseline in Total Bilirubin Day 29	-24.66 umol/L Standard Deviation 15.026	-26.14 umol/L Standard Deviation 22.345	—	—
Absolute Change From Baseline in Total Bilirubin Day 36	-23.96 umol/L Standard Deviation 15.945	-25.31 umol/L Standard Deviation 27.658	—	—
Absolute Change From Baseline in Total Bilirubin Day 43	-24.66 umol/L Standard Deviation 14.552	-25.14 umol/L Standard Deviation 23.727	—	—
Absolute Change From Baseline in Total Bilirubin Day 57	-24.16 umol/L Standard Deviation 13.946	-22.81 umol/L Standard Deviation 21.233	—	—
Absolute Change From Baseline in Total Bilirubin Day 71	-23.16 umol/L Standard Deviation 15.154	-27.92 umol/L Standard Deviation 24.924	—	—
Absolute Change From Baseline in Total Bilirubin Day 85	-23.66 umol/L Standard Deviation 14.595	-28.42 umol/L Standard Deviation 26.075	—	—
Absolute Change From Baseline in Total Bilirubin Day 92	-21.66 umol/L Standard Deviation 13.985	-27.87 umol/L Standard Deviation 25.234	—	—
Absolute Change From Baseline in Total Bilirubin Day 113	-21.06 umol/L Standard Deviation 15.026	-26.87 umol/L Standard Deviation 23.200	—	—
Absolute Change From Baseline in Total Bilirubin Day 127	-22.18 umol/L Standard Deviation 13.357	-27.79 umol/L Standard Deviation 26.965	—	—
Absolute Change From Baseline in Total Bilirubin Day 141	-22.46 umol/L Standard Deviation 14.404	-18.23 umol/L Standard Deviation 9.473	—	—
Absolute Change From Baseline in Total Bilirubin Day 155	-19.73 umol/L Standard Deviation 12.376	-16.23 umol/L Standard Deviation 9.565	—	—
Absolute Change From Baseline in Total Bilirubin Day 169	-21.66 umol/L Standard Deviation 13.383	-14.83 umol/L Standard Deviation 10.281	—	—
Absolute Change From Baseline in Total Bilirubin Day 197	-24.21 umol/L Standard Deviation 13.678	-23.71 umol/L Standard Deviation 28.849	—	—
Absolute Change From Baseline in Total Bilirubin Day 225	-23.06 umol/L Standard Deviation 12.410	-30.06 umol/L Standard Deviation 36.183	—	—
Absolute Change From Baseline in Total Bilirubin Day 253	-21.36 umol/L Standard Deviation 12.192	-24.21 umol/L Standard Deviation 30.342	—	—
Absolute Change From Baseline in Total Bilirubin Day 281	-23.46 umol/L Standard Deviation 12.150	-16.54 umol/L Standard Deviation 8.694	—	—
Absolute Change From Baseline in Total Bilirubin Day 309	-22.86 umol/L Standard Deviation 12.078	-11.21 umol/L Standard Deviation 10.635	—	—
Absolute Change From Baseline in Total Bilirubin Day 337	-22.76 umol/L Standard Deviation 13.248	-28.71 umol/L Standard Deviation 29.338	—	—
Absolute Change From Baseline in Total Bilirubin Day 393	-19.73 umol/L Standard Deviation 15.644	-28.00 umol/L Standard Deviation 27.769	—	—
Absolute Change From Baseline in Total Bilirubin Day 449	-24.64 umol/L Standard Deviation 13.021	-23.50 umol/L Standard Deviation 25.603	—	—
Absolute Change From Baseline in Total Bilirubin Day 505	-27.30 umol/L Standard Deviation 12.450	-25.81 umol/L Standard Deviation 24.978	—	—
Absolute Change From Baseline in Total Bilirubin Day 561	-21.98 umol/L Standard Deviation 14.718	-21.10 umol/L Standard Deviation 30.888	—	—
Absolute Change From Baseline in Total Bilirubin Day 617	-28.85 umol/L Standard Deviation 11.516	-23.47 umol/L Standard Deviation 21.451	—	—
Absolute Change From Baseline in Total Bilirubin Day 673	-27.58 umol/L Standard Deviation 13.453	-24.50 umol/L Standard Deviation 25.562	—	—
Absolute Change From Baseline in Total Bilirubin Day 729	-23.64 umol/L Standard Deviation 12.971	-32.13 umol/L Standard Deviation 28.799	—	—
Absolute Change From Baseline in Total Bilirubin Day 785	-11.54 umol/L Standard Deviation 5.370	-26.67 umol/L Standard Deviation 33.656	—	—
Absolute Change From Baseline in Total Bilirubin Day 841	-20.49 umol/L Standard Deviation 12.006	-29.42 umol/L Standard Deviation 32.316	—	—
Absolute Change From Baseline in Total Bilirubin Day 897	-24.49 umol/L Standard Deviation 13.627	-16.00 umol/L Standard Deviation 7.542	—	—
Absolute Change From Baseline in Total Bilirubin Day 953	-23.92 umol/L Standard Deviation 14.707	—	—	—
Absolute Change From Baseline in Total Bilirubin Day 1009	-23.92 umol/L Standard Deviation 14.204	—	—	—
Absolute Change From Baseline in Total Bilirubin Day 1065	-25.65 umol/L Standard Deviation 13.844	—	—	—
Absolute Change From Baseline in Total Bilirubin Day 1121	-23.35 umol/L Standard Deviation 14.363	—	—	—
Absolute Change From Baseline in Total Bilirubin Day 1177	-29.78 umol/L Standard Deviation 11.559	—	—	—
Absolute Change From Baseline in Total Bilirubin Day 1233	-28.78 umol/L Standard Deviation 12.328	—	—	—

SECONDARY outcome

Timeframe: Up to 46 months

Population: The overall number of participants analyzed represents the participants in the safety analysis set. Safety analysis set included all patients that received any study drug.

Number of participants with on study transfusions from packed RBC units was collected.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Number of Participants With on Study Transfusions From Packed RBC Units	2 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: Day 1, 29, 169, 337

Population: The overall number of participants analyzed represents the participants in the PK analysis set. The Pharmacokinetic (PK) analysis set is defined as patients with at least one available valid PK concentration measurement, who received any study drug and with no protocol deviations that impact on PK data. The number analyzed per row represents the participants with a valid Cmax value for that particular visit.

Cmax is the maximum (peak) observed plasma drug concentration after single dose administration (mass x volume-1). PK assessment parameters were determined using the actual recorded sampling times and non-compartmental methods. In Cohort 2, patients were supposed to be orally administered iptacopan 50 mg b.i.d. in addition to SoC; this was increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values. One patient in Cohort 2 was orally administered iptacopan 25 mg at day 1 due to a dosing error.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=1 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total n=6 Participants Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC n=3 Participants Orally administered iptacopan 200 mg b.i.d. at the respective visit
Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) Day 1	3400 ng/mL Standard Deviation 1060	1610 ng/mL	1570 ng/mL Standard Deviation 366	—
Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) Day 29	3500 ng/mL Standard Deviation 1340	—	1770 ng/mL Standard Deviation 469	—
Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) Day 169	3530 ng/mL Standard Deviation 853	—	1180 ng/mL	3130 ng/mL Standard Deviation 824
Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) Day 337	4030 ng/mL Standard Deviation 1140	—	2470 ng/mL	4370 ng/mL Standard Deviation 1790

SECONDARY outcome

Timeframe: day 1, 29, 169, 337

Population: The overall number of participants analyzed represents the participants in the PK analysis set. The number analyzed per row represents the participants with a valid AUCtau value for that particular visit.

The AUCtau is the area under the plasma concentration-time curve calculated to the end of a dosing interval (tau) at steady-state. PK assessment parameters were determined using the actual recorded sampling times and non-compartmental methods. In Cohort 2, patients were supposed to be orally administered iptacopan 50 mg b.i.d. in addition to SoC; this was increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values. One patient in Cohort 2 was orally administered iptacopan 25 mg at day 1 due to a dosing error.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=1 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total n=6 Participants Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC n=3 Participants Orally administered iptacopan 200 mg b.i.d. at the respective visit
Pharmacokinetics Profile: Area Under the Curve (AUC) Tau Day 1	18200 h*ng/mL Standard Deviation 6700	9470 h*ng/mL	8620 h*ng/mL Standard Deviation 1310	—
Pharmacokinetics Profile: Area Under the Curve (AUC) Tau Day 29	24400 h*ng/mL Standard Deviation 8720	—	14800 h*ng/mL Standard Deviation 4100	—
Pharmacokinetics Profile: Area Under the Curve (AUC) Tau Day 169	25600 h*ng/mL Standard Deviation 7570	—	10700 h*ng/mL	23900 h*ng/mL Standard Deviation 5920
Pharmacokinetics Profile: Area Under the Curve (AUC) Tau Day 337	26900 h*ng/mL Standard Deviation 7640	—	16900 h*ng/mL	37800 h*ng/mL Standard Deviation 15500

SECONDARY outcome

Timeframe: Day 1, 29, 169, 337

Tmax is the time to reach maximum (peak) plasma drug concentration after single dose administration (time). PK assessment parameters were determined using the actual recorded sampling times and non-compartmental methods. In Cohort 2, patients were supposed to be orally administered iptacopan 50 mg b.i.d. in addition to SoC; this was increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values. One patient in Cohort 2 was orally administered iptacopan 25 mg at day 1 due to a dosing error.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=1 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total n=6 Participants Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC n=3 Participants Orally administered iptacopan 200 mg b.i.d. at the respective visit
Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) Day 1	1.50 hours Interval 1.0 to 6.0	2.00 hours Interval 2.0 to 2.0	2.00 hours Interval 2.0 to 2.0	—
Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) Day 29	2.00 hours Interval 1.0 to 2.0	—	2.04 hours Interval 2.0 to 4.0	—
Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) Day 169	2.00 hours Interval 1.0 to 4.0	—	4.00 hours Interval 4.0 to 4.0	2.00 hours Interval 1.83 to 2.0
Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) Day 337	2.00 hours Interval 1.0 to 2.0	—	2.03 hours Interval 2.03 to 2.03	2.00 hours Interval 1.05 to 5.0

SECONDARY outcome

Timeframe: Screening, Baseline, Day 2,8,15,22,29,36,43,57,71,85,92,113,127,141,155,169,197,225,253,281,309,337,393,449,505,561,617,673,729,729,785,841,897,953,1009,1065,1121,1177,1233

Population: The safety analysis set is defined as patients that received any study drug. The number analyzed per row represents the participants with a valid erythrocytes value for that particular visit

Erythrocytes levels were used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan.

Outcome measures

Outcome measures
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Red Blood Cell Count: Mean Erythrocytes Levels Screening	3.12 10^12 cells/L Standard Deviation 0.887	2.42 10^12 cells/L Standard Deviation 0.427	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Baseline	2.73 10^12 cells/L Standard Deviation 0.466	2.40 10^12 cells/L Standard Deviation 0.442	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 1	2.67 10^12 cells/L Standard Deviation 0.615	2.16 10^12 cells/L Standard Deviation 0.498	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 2	2.70 10^12 cells/L Standard Deviation 0.485	2.17 10^12 cells/L Standard Deviation 0.520	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 8	3.17 10^12 cells/L Standard Deviation 0.585	3.00 10^12 cells/L Standard Deviation 0.812	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 15	3.43 10^12 cells/L Standard Deviation 0.723	3.23 10^12 cells/L Standard Deviation 0.794	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 22	3.58 10^12 cells/L Standard Deviation 0.835	3.57 10^12 cells/L Standard Deviation 0.900	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 29	3.72 10^12 cells/L Standard Deviation 0.857	3.62 10^12 cells/L Standard Deviation 0.870	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 36	3.75 10^12 cells/L Standard Deviation 0.753	3.62 10^12 cells/L Standard Deviation 0.804	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 43	3.67 10^12 cells/L Standard Deviation 0.807	3.55 10^12 cells/L Standard Deviation 0.758	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 57	3.69 10^12 cells/L Standard Deviation 0.852	3.72 10^12 cells/L Standard Deviation 0.574	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 71	3.50 10^12 cells/L Standard Deviation 0.787	3.48 10^12 cells/L Standard Deviation 0.591	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 85	3.65 10^12 cells/L Standard Deviation 0.841	3.60 10^12 cells/L Standard Deviation 0.520	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 92	3.76 10^12 cells/L Standard Deviation 0.828	3.56 10^12 cells/L Standard Deviation 0.483	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 113	3.58 10^12 cells/L Standard Deviation 0.807	3.58 10^12 cells/L Standard Deviation 0.444	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 127	3.69 10^12 cells/L Standard Deviation 0.822	3.75 10^12 cells/L Standard Deviation 0.265	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 141	3.64 10^12 cells/L Standard Deviation 0.799	3.44 10^12 cells/L Standard Deviation 0.493	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 155	3.53 10^12 cells/L Standard Deviation 0.815	3.52 10^12 cells/L Standard Deviation 0.432	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 169	3.62 10^12 cells/L Standard Deviation 0.826	3.54 10^12 cells/L Standard Deviation 0.378	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 197	3.68 10^12 cells/L Standard Deviation 0.774	3.77 10^12 cells/L Standard Deviation 0.577	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 225	3.70 10^12 cells/L Standard Deviation 0.894	3.43 10^12 cells/L Standard Deviation 0.513	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 253	3.62 10^12 cells/L Standard Deviation 0.930	3.45 10^12 cells/L Standard Deviation 0.412	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 281	3.81 10^12 cells/L Standard Deviation 0.875	3.73 10^12 cells/L Standard Deviation 0.403	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 309	3.50 10^12 cells/L Standard Deviation 0.728	3.58 10^12 cells/L Standard Deviation 0.427	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 337	3.50 10^12 cells/L Standard Deviation 0.714	3.75 10^12 cells/L Standard Deviation 0.580	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 393	3.63 10^12 cells/L Standard Deviation 0.876	4.00 10^12 cells/L Standard Deviation 0.356	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 449	3.80 10^12 cells/L Standard Deviation 0.920	3.94 10^12 cells/L Standard Deviation 0.378	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 505	3.63 10^12 cells/L Standard Deviation 1.053	3.92 10^12 cells/L Standard Deviation 0.360	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 561	3.47 10^12 cells/L Standard Deviation 0.937	3.92 10^12 cells/L Standard Deviation 0.370	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 617	3.80 10^12 cells/L Standard Deviation 1.149	3.85 10^12 cells/L Standard Deviation 0.389	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 673	3.74 10^12 cells/L Standard Deviation 0.716	3.86 10^12 cells/L Standard Deviation 0.270	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 729	3.74 10^12 cells/L Standard Deviation 1.021	3.93 10^12 cells/L Standard Deviation 0.150	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 785	2.83 10^12 cells/L Standard Deviation 0.618	3.78 10^12 cells/L Standard Deviation 0.263	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 841	3.64 10^12 cells/L Standard Deviation 1.081	3.80 10^12 cells/L Standard Deviation 0.294	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 897	3.89 10^12 cells/L Standard Deviation 1.123	3.95 10^12 cells/L Standard Deviation 0.071	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 953	3.62 10^12 cells/L Standard Deviation 1.196	—	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 1009	3.61 10^12 cells/L Standard Deviation 1.316	—	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 1065	3.87 10^12 cells/L Standard Deviation 1.073	—	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 1121	3.69 10^12 cells/L Standard Deviation 1.006	—	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 1177	4.06 10^12 cells/L Standard Deviation 0.829	—	—	—
Red Blood Cell Count: Mean Erythrocytes Levels Day 1233	4.14 10^12 cells/L Standard Deviation 0.844	—	—	—

Adverse Events

Cohort 1: LNP023 200mg Bid + SoC

Serious events: 4 serious events

Other events: 10 other events

Deaths: 3 deaths

Cohort 2: LNP023 50mg Bid + SoC

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Cohort 2: LNP023 200mg Bid + SoC

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Total

Serious events: 6 serious events

Other events: 16 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 participants at risk Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg Bid + SoC n=6 participants at risk Orally administered iptacopan 50 mg b.i.d. in Part 1 and iptacopan 50 mg b.i.d. or 200 mg b.i.d. in Part 2 in addition to SoC. This arm summarizes all events that started when treated with iptacopan 50 mg b.i.d. in Cophort 2	Cohort 2: LNP023 200mg Bid + SoC n=5 participants at risk Orally administered iptacopan 50 mg b.i.d. in Part 1 and iptacopan 50 mg b.i.d. or 200 mg b.i.d. in Part 2 in addition to SoC. This arm summarizes all events that started when treated with iptacopan 200 mg b.i.d. in Cohort 2. Total number at risk only includes patients who received LNP023 200mg bid.	Total n=16 participants at risk Total
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoproliferative disorder	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the oral cavity	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Nervous system disorders Haemorrhage intracranial	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Renal and urinary disorders Urinary bladder polyp	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	20.0% 1/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Vascular disorders Penetrating aortic ulcer	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Infections and infestations Escherichia bacteraemia	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Infections and infestations Urinary tract infection	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	20.0% 1/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	0.00% 0/6 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	20.0% 1/5 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.	6.2% 1/16 • Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.

Other adverse events

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

Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=5 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 8	-5.59 percentage of PNH RBC Standard Deviation 6.541	-1.24 percentage of PNH RBC Standard Deviation 4.510	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 22	-8.02 percentage of PNH RBC Standard Deviation 8.198	-2.35 percentage of PNH RBC Standard Deviation 5.620	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 29	-11.64 percentage of PNH RBC Standard Deviation 7.990	-4.36 percentage of PNH RBC Standard Deviation 2.662	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 57	-8.90 percentage of PNH RBC Standard Deviation 5.778	-5.35 percentage of PNH RBC Standard Deviation 2.357	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 92	-8.70 percentage of PNH RBC Standard Deviation 6.310	-6.21 percentage of PNH RBC Standard Deviation 0.866	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 113	-13.65 percentage of PNH RBC Standard Deviation 9.927	-5.10 percentage of PNH RBC Standard Deviation 2.478	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 141	-13.18 percentage of PNH RBC Standard Deviation 11.489	-6.19 percentage of PNH RBC Standard Deviation 4.818	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 169	-11.06 percentage of PNH RBC Standard Deviation 5.874	-4.66 percentage of PNH RBC Standard Deviation 3.175	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 253	-10.08 percentage of PNH RBC Standard Deviation 6.259	-4.36 percentage of PNH RBC Standard Deviation 1.538	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 337	-11.21 percentage of PNH RBC Standard Deviation 6.118	-4.08 percentage of PNH RBC Standard Deviation 3.340	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 505	-16.04 percentage of PNH RBC Standard Deviation 2.732	-6.76 percentage of PNH RBC Standard Deviation 2.650	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 673	-15.19 percentage of PNH RBC Standard Deviation 2.805	—	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 785	-1.00 percentage of PNH RBC	—	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 953	-15.28 percentage of PNH RBC Standard Deviation 3.528	—	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 1121	-0.94 percentage of PNH RBC	—	—	—
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC Day 1233	-12.74 percentage of PNH RBC	—	—	—

Measure	Cohort 1: LNP023 200mg Bid + SoC n=10 Participants Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.	Cohort 2: LNP023 50mg/200mg Bid + SoC n=6 Participants Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.	Total Participants from Cohort 1 and Cohort 2	Cohort 2: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. at the respective visit
Mean PNH Clone Size Day 1 pre dose	54.75 percentage of PNH RBC Standard Deviation 32.536	46.10 percentage of PNH RBC Standard Deviation 31.436	—	—
Mean PNH Clone Size Day 8	66.32 percentage of PNH RBC Standard Deviation 29.570	64.45 percentage of PNH RBC Standard Deviation 27.711	—	—
Mean PNH Clone Size Day 22	75.23 percentage of PNH RBC Standard Deviation 23.458	79.37 percentage of PNH RBC Standard Deviation 20.270	—	—
Mean PNH Clone Size Day 29	75.34 percentage of PNH RBC Standard Deviation 20.837	78.87 percentage of PNH RBC Standard Deviation 17.642	—	—
Mean PNH Clone Size Day 57	85.87 percentage of PNH RBC Standard Deviation 15.660	86.45 percentage of PNH RBC Standard Deviation 12.576	—	—
Mean PNH Clone Size Day 92	89.20 percentage of PNH RBC Standard Deviation 16.861	85.38 percentage of PNH RBC Standard Deviation 12.939	—	—
Mean PNH Clone Size Day 113	89.28 percentage of PNH RBC Standard Deviation 18.936	86.02 percentage of PNH RBC Standard Deviation 9.626	—	—
Mean PNH Clone Size Day 141	93.91 percentage of PNH RBC Standard Deviation 6.105	80.25 percentage of PNH RBC Standard Deviation 6.638	—	—
Mean PNH Clone Size Day 169	87.60 percentage of PNH RBC Standard Deviation 19.644	83.69 percentage of PNH RBC Standard Deviation 11.187	—	—
Mean PNH Clone Size Day 253	90.30 percentage of PNH RBC Standard Deviation 18.176	82.28 percentage of PNH RBC Standard Deviation 12.649	—	—
Mean PNH Clone Size Day 337	88.69 percentage of PNH RBC Standard Deviation 20.381	91.68 percentage of PNH RBC Standard Deviation 11.905	—	—
Mean PNH Clone Size Day 505	98.33 percentage of PNH RBC Standard Deviation 1.738	88.45 percentage of PNH RBC Standard Deviation 10.419	—	—
Mean PNH Clone Size Day 673	97.45 percentage of PNH RBC Standard Deviation 2.370	92.48 percentage of PNH RBC Standard Deviation 6.626	—	—
Mean PNH Clone Size Day 785	83.61 percentage of PNH RBC Standard Deviation 9.327	—	—	—
Mean PNH Clone Size Day 953	96.08 percentage of PNH RBC Standard Deviation 3.825	—	—	—
Mean PNH Clone Size Day 1121	93.74 percentage of PNH RBC Standard Deviation 7.410	—	—	—
Mean PNH Clone Size Day 1233	69.83 percentage of PNH RBC Standard Deviation 43.045	—	—	—