Trial Outcomes & Findings for Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan. (NCT NCT05630001)

NCT ID: NCT05630001

Last Updated: 2026-01-13

Results Overview

Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. The estimation of change from baseline in Hb levels was handled by the hypothetical strategy where participants were assumed as if they did not receive RBC transfusions while on treatment (RBC transfusions were expected to be rare). Assuming that participants had stable Hb levels at study entry, the mean change from baseline in Hb level between Day 126 and Day 168 was expected to be unchanged should participants have continued on anti-C5 treatment. Non-inferiority of iptacopan was therefore tested by the null hypothesis (H0) against the alternate hypothesis (H1) comparing the mean change from baseline in Hb level in iptacopan between Day 126 and Day 168 (μ) to -1 g/dL: H0: μ \<= -1, H1: μ \> -1.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 52 participants
• Primary outcome timeframe: Baseline, Day 126 to Day 168
• Results posted on: 2026-01-13

Participant Flow

A total of 23 centers; 9 in United States, 4 in Germany, 3 in France, 2 in the United Kingdom, 2 in Italy and one each in Spain, Turkey and Republic of Korea enrolled participants.

The study consisted of a screening period up to 8 weeks.

Participant milestones

Measure	LNP023 200mg b.i.d. Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Overall Study STARTED	52
Overall Study COMPLETED	51
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	LNP023 200mg b.i.d. Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Overall Study Adverse Event	1

Baseline Characteristics

Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.

Baseline characteristics by cohort

Measure	LNP023 200mg b.i.d. n=52 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Age, Categorical <=18 years	0 Participants n=210 Participants
Age, Categorical Between 18 and 65 years	48 Participants n=210 Participants
Age, Categorical >=65 years	4 Participants n=210 Participants
Age, Continuous	46.0 years STANDARD_DEVIATION 13.67 • n=210 Participants
Sex: Female, Male Female	20 Participants n=210 Participants
Sex: Female, Male Male	32 Participants n=210 Participants
Race/Ethnicity, Customized White	35 Participants n=210 Participants
Race/Ethnicity, Customized Asian	4 Participants n=210 Participants
Race/Ethnicity, Customized Not Reported	9 Participants n=210 Participants
Race/Ethnicity, Customized Unknown	4 Participants n=210 Participants

PRIMARY outcome

Timeframe: Baseline, Day 126 to Day 168

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at baseline and Day 126 and Day 168.

Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline.

Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1.

The estimation of change from baseline in Hb levels was handled by the hypothetical strategy where participants were assumed as if they did not receive RBC transfusions while on treatment (RBC transfusions were expected to be rare).

Assuming that participants had stable Hb levels at study entry, the mean change from baseline in Hb level between Day 126 and Day 168 was expected to be unchanged should participants have continued on anti-C5 treatment. Non-inferiority of iptacopan was therefore tested by the null hypothesis (H0) against the alternate hypothesis (H1) comparing the mean change from baseline in Hb level in iptacopan between Day 126 and Day 168 (μ) to -1 g/dL: H0: μ <= -1, H1: μ > -1.

Outcome measures

Measure	LNP023 200mg b.i.d. n=51 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority	2.01 g/dL Interval 1.74 to 2.29

SECONDARY outcome

Timeframe: Baseline, Day 126 to Day 168

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at baseline and Day 126 and Day 168.

Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline.

Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1.

Outcome measures

Measure	LNP023 200mg b.i.d. n=51 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Superiority	2.01 g/dL Interval 1.74 to 2.29

SECONDARY outcome

Timeframe: Day 126 to Day 168

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at Day 126 and Day 168.

Response defined as Hb ≥12 g/dL assessed between visits Day 126 and Day 168 in the absence of RBC transfusions, on three out of four measurements taken at the visits occurring in last six weeks

Outcome measures

Measure	LNP023 200mg b.i.d. n=51 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Proportion of Hematological Responders to Iptacopan Treatment	92.7 Proportion of participants Interval 84.6 to 98.1

SECONDARY outcome

Timeframe: Day 1 to Day 168

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned.

Number of participants with absence of administration of packed RBC transfusions between Day 1 and Day 168

Outcome measures

Measure	LNP023 200mg b.i.d. n=52 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Proportion of Participants Who Remain Free From Transfusions	100.0 Proportion of participants Interval 93.1 to 100.0

SECONDARY outcome

Timeframe: Baseline, Day 126 to Day 168

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at Day 126 and Day 168.

Change from baseline in ARC levels as mean of visits between Day 126 and Day 168

Outcome measures

Measure	LNP023 200mg b.i.d. n=51 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Change From Baseline in Absolute Reticulocytes Count (ARC) Levels	-89.19 10^9 cells/L Interval -95.47 to -82.92

SECONDARY outcome

Timeframe: Baseline, Day 126 to Day 168

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at Day 126 and Day 168.

Percentage change from baseline in LDH levels as mean of visits between Day 126 and Day 168

Outcome measures

Measure	LNP023 200mg b.i.d. n=51 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Levels	-1.30 Percent change from baseline in LDH Interval -6.56 to 4.26

SECONDARY outcome

Timeframe: Baseline, Day 84 and Day 168

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at baseline, Day 84 and Day 168.

Difference in scores of the Treatment Satisfaction Questionnaire for Medication(TSQM-9) between baseline and Day 84 and Day 168 assessed after switching from SoC (anti-C5) to iptacopan.

TSQM-9 is a patient reported outcomes measure that was designed to assess patients' satisfaction with medication across three domains of effectiveness, convenience and global satisfaction. The TSQM-9 contains 3 questions in each domain. Domain scores range from 0 - 100 with higher scores representing better outcomes for the domain.

Outcome measures

Measure	LNP023 200mg b.i.d. n=50 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire TSQMS1-Effectiveness Day 84	15.08 score on a scale Interval 9.6 to 20.57
Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire TSQMS1-Global Satisfaction Day 84	14.26 score on a scale Interval 9.79 to 18.72
Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire TSQMS1-Global Satisfaction Day 168	18.53 score on a scale Interval 12.87 to 24.19
Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire TSQMS1-Effectiveness Day 168	12.54 score on a scale Interval 5.58 to 19.49
Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire TSQMS1-Convenience Day 84	20.34 score on a scale Interval 13.68 to 26.99
Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire TSQMS1-Convenience 168	23.86 score on a scale Interval 17.62 to 30.1

SECONDARY outcome

Timeframe: Baseline, Day 84 and Day 168

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at Day 84 and Day 168.

Change from baseline in patient-reported scores for the functional assessment of chronic illness therapy - Fatigue (FACIT-F) collected at Day 84 and Day 168.

The FACIT-F is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best.

Outcome measures

Measure	LNP023 200mg b.i.d. n=50 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Change From Baseline in Fatigue Score Using FACIT-F Questionnaire Day 84	4.88 score on a scale Interval 3.23 to 6.53
Change From Baseline in Fatigue Score Using FACIT-F Questionnaire Day 168	4.29 score on a scale Interval 1.74 to 6.85

SECONDARY outcome

Timeframe: Up to 168 Days

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned.

Wilson method is used to calculate the confidence interval for the proportion of patients who had events.

The breakthrough is defined clinical if either there is a decrease in hemoglobin levels equal to or more than 2 g/dL (compared to the latest assessment) or if patients present signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia or any other significant clinical PNH-related signs & symptoms, in presence of laboratory evidence of intravascular hemolysis.

Outcome measures

Measure	LNP023 200mg b.i.d. n=52 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Percentage of Patients Who Had Breakthrough Hemolysis (BTH) Event	0.00 Percentage of patients with BTH events Interval 0.0 to 0.14

SECONDARY outcome

Timeframe: Up to 168 Days

Population: Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned.

A MAVE is defined as: acute peripheral vascular occlusion, amputation (non-traumatic; nondiabetic), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, dermal thrombosis, gangrene (non-traumatic; nondiabetic), hepatic/portal vein thrombosis (Budd-Chiari syndrome), mesenteric/visceral arterial thrombosis or infarction, mesenteric/visceral vein thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial thrombosis, renal vein thrombosis, thrombophlebitis / deep vein thrombosis, transient ischemic attack, unstable angina or other.

Outcome measures

Measure	LNP023 200mg b.i.d. n=52 Participants Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Percentage of Patients Who Had Major Adverse Vascular Events (MAVEs)	0.00 Percentage of patients with MAVEs Interval 0.0 to 0.14

Adverse Events

LNP023 200mg b.i.d.

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	LNP023 200mg b.i.d. n=52 participants at risk Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
General disorders and administration site conditions Pyrexia	1.9% 1/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
Infections and infestations Pneumonia bacterial	1.9% 1/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
Injury, poisoning and procedural complications Subdural haematoma	1.9% 1/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days

Other adverse events

Measure	LNP023 200mg b.i.d. n=52 participants at risk Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
Gastrointestinal disorders Diarrhoea	11.5% 6/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
Gastrointestinal disorders Nausea	11.5% 6/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
General disorders and administration site conditions Fatigue	7.7% 4/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
Infections and infestations Nasopharyngitis	11.5% 6/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
Infections and infestations Upper respiratory tract infection	5.8% 3/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
Nervous system disorders Headache	17.3% 9/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.8% 3/52 • Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

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

Restriction type: OTHER