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CompletedNCT03439839Updated Jun 12, 2024Results posted

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

A Phase 2 interventional study of iptacopan and Standard of Care in Paroxysmal Nocturnal Hemoglobinuria (PNH) With Signs of Active Hemolysis, sponsored by Novartis Pharmaceuticals. Completed at 3 sites in 3 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-06-12.

Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
16
Allocation
Non-randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

This was a Phase 2, open label, single arm, multiple dose study to assess efficacy, safety, pharmacokinetics and pharmacodynamics of iptacopan when administered in addition to Standard of care (SoC) in patients with paroxysmal nocturnal hemoglobinuria (PNH) with signs of active hemolysis.

Read the detailed description

LNP023 is a novel oral small molecular weight compound that inhibits factor B (FB) of the alternative pathway (AP). Blockade of the AP with oral LNP023 has the potential to prevent both intra - and extravascular hemolysis.

This two-cohort study consisted of a screening period of up to 68 days, a baseline visit, and Treatment periods Part 1 and Part 2. The planned duration of Treatment Part 1 was 13 weeks; the planned duration of Treatment Part 2 (treatment extension for patients who benefit from LNP023 treatment in Part 1 of the study based on reduced hemolytic parameters) was between approximately 2 to 3 years.

Cohort 1: Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.

Cohort 2: 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.

End of Study (EoS) visit happened 2 weeks after last LNP023 administration for patients not joining the roll over extension program (REP).

A safety follow-up call was conducted 30 days after last administration of study treatment (applicable only for patients not joining the REP).

02

Conditions studied

  • Paroxysmal Nocturnal Hemoglobinuria (PNH) With Signs of Active Hemolysis

Keywords

  • Complement
  • alternative pathway
  • paroxysmal nocturnal hemoglobinuria
  • hemolysis
03

In context

Hemoglobinuria, Paroxysmal

191 studies on the registry are indexed under Hemoglobinuria, Paroxysmal; 49 are open to participants now.

This study's enrollment of 16 is below the median of 33 across 150 interventional studies indexed under Hemoglobinuria, Paroxysmal.

Browse Hemoglobinuria, Paroxysmal studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.

Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.

Browse Novartis Pharmaceuticals studies →All Novartis studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Male and female patients between the age of 18-80 (inclusive) at Baseline with a diagnosis of PNH based on documented clone size of ≥10% by RBCs and/or granulocytes, measured by glycosylphosphatidylinositol (GPI)-deficiency on flow cytometry (screening or medical history data acceptable).
  2. For Cohort 1 only: LDH values ≥1.5 × (ULN) range for at least 3 pre-SoC dosing measurements taken in relation to 3 different SoC dosing dates over a maximum of 10 weeks prior to Day 1 (Screening, Baseline, or medical history data acceptable). All other Screening pre-SoC LDH values must be >1 × ULN range (for pre-SoC samples collected at the same day as SoC administration).
  3. For Cohort 2 only: LDH values ≥1.25 × ULN range for at least 3 pre-SoC dosing measurements taken in relation to 3 different SoC dosing dates over a maximum of 10 weeks prior to Day 1 (Screening, Baseline, or medical history data acceptable). All other Screening pre-SoC LDH values must be >1 × ULN range (for pre-SoC samples collected at the same day as SoC administration).
  4. For Cohort 2 only: level \<10.5 g/dL at Baseline.
  5. PNH patients on stable regimen of SoC complement blockade (monoclonal antibody with anti C5 activity) for at least 3 months prior to first treatment with iptacopan.
  6. Previous vaccination against N. meningitidis types A, C, Y and W-135 is required at least 4 weeks prior to first dosing with iptacopan. Vaccination against N. meningitidis type B should be conducted if available and acceptable by local regulations, at least 4 weeks prior to first dosing with iptacopan. If iptacopan treatment must start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment must be initiated.
  7. Previous vaccination for the prevention of S. pneumoniae and H. influenzae at least 4 weeks prior to first dosing with iptacopan. If iptacopan treatment must start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment must be initiated.

Exclusion criteria

Exclusion Criteria:

  1. Known or suspected hereditary complement deficiency at Screening.
  2. History of hematopoietic stem cell transplantation as verified both at Screening and at Baseline (unless baseline was skipped).
  3. Patients with laboratory evidence of bone marrow failure.
  4. A positive (HIV), or test result at Screening.
  5. Presence or suspicion (based on judgment of the Investigator) of active infection within 2 weeks prior to first dose of iptacopan, or history of severe recurrent bacterial infections.
  6. History of recurrent meningitis, history of meningococcal infections despite vaccination as verified both at Screening and at Baseline (unless Baseline was skipped).
  7. Patients on agents such as (but not limited to) cyclosporine, mycophenolate mofetil, tacrolimus, cyclophosphamide, methotrexate less than 8 weeks prior to first treatment with iptacopan unless on a stable regimen for at least 3 months prior to first iptacopan dose.
  8. Systemic administered at the dose of ≥10 mg per day prednisone equivalent within less than 4 weeks prior to first treatment with iptacopan.
  9. Severe concurrent co-morbidities; e.g., patients with severe kidney disease (dialysis), advanced cardiac disease (New York Heart disease Association () class IV), severe pulmonary arterial hypertension (World Health Organization (WHO) class IV), unstable thrombotic event not amenable to active treatment as judged by the Investigator both at Screening and at Baseline (unless Baseline was skipped).
Terms in these criteria, in plain language(8)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
16 participants (actual)

Study arms

  • Experimental
    Cohort 1: LNP023 200mg bid + SoC

    Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2

    Drug: iptacopan · Combination Product: Standard of Care

  • Experimental
    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.

    Drug: iptacopan · Combination Product: Standard of Care

Interventions

  • Drugiptacopan

    iptacopan bid orally administered

    Also known as: LNP023

  • Combination productStandard of Care

    Standard of Care (SoC) is defined as an antibody with anti C5 activity. At the time of study start, eculizumab was the only available SoC; eculizumab will be hereafter referred to as SoC.

06

What researchers measure

Primary outcomes

  1. Percent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92

    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.

    Time frame: Baseline and Day 92

Secondary outcomes

  1. Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level

    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.

    Time frame: Baseline, day 8, 15, 29, 57 and 92

  2. Absolute Change From Baseline in Hemoglobin

    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.

    Time frame: 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

  3. Absolute Change From Baseline in Free Hemoglobin

    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.

    Time frame: 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

  4. Absolute Change From Baseline in Reticulocytes Count

    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.

    Time frame: 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

  5. Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC

    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.

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

  6. Mean PNH Clone Size

    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.

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

  7. Mean Haptoglobin Levels

    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.

    Time frame: 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

  8. Absolute Change From Baseline in Total Bilirubin

    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.

    Time frame: 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

  9. Number of Participants With on Study Transfusions From Packed RBC Units

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

    Time frame: Up to 46 months

  10. Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax)

    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.

    Time frame: Day 1, 29, 169, 337

  11. Pharmacokinetics Profile: Area Under the Curve (AUC) Tau

    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.

    Time frame: day 1, 29, 169, 337

  12. Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax)

    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.

    Time frame: Day 1, 29, 169, 337

  13. Red Blood Cell Count: Mean Erythrocytes Levels

    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.

    Time frame: 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

07

Results

Posted Jan 3, 2024

Participant flow

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

Participant flow — Overall Study
MilestoneCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Started106
Completed76
Not completed30
Withdrew: Death30

Outcome measures

PrimaryPercent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92

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.

Time frame:
Baseline and Day 92
Reported as:
Mean · Percent change from Baseline
Percent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92
Percent change from BaselineCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoCTotal
Percent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92-53.59 (-61.38 to -45.79)-25.56 (-46.92 to -4.20)-43.58 (-53.57 to -33.58)
SecondaryAbsolute Change From Baseline in Lactate Dehydrogenase (LDH) Level

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.

Time frame:
Baseline, day 8, 15, 29, 57 and 92
Reported as:
Mean · U/L
Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level
U/LCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoCTotal
Day 8-272.57 (-349.07 to -196.07)-145.22 (-196.30 to -94.15)-224.81 (-279.88 to -169.74)
Day 15-353.97 (-486.36 to -221.57)-175.07 (-247.55 to -102.59)-294.33 (-388.42 to -200.24)
Day 29-368.17 (-510.15 to -226.18)-191.22 (-258.88 to -123.56)-301.81 (-395.89 to -207.73)
Day 57-317.07 (-459.11 to -175.03)-135.89 (-212.28 to -59.50)-249.13 (-344.24 to -154.01)
Day 92-330.52 (-488.02 to -173.01)-109.07 (-196.69 to -21.45)-251.43 (-361.88 to -140.98)
SecondaryAbsolute Change From Baseline in Hemoglobin

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.

Time frame:
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
Reported as:
Mean · g/L
Absolute Change From Baseline in Hemoglobin
g/LCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Day 1-4.05 ± 8.750-6.67 ± 7.218
Day 2-3.65 ± 7.638-8.06 ± 6.830
Day 812.85 ± 9.22820.11 ± 13.475
Day 1520.25 ± 10.12226.44 ± 10.047
Day 2224.15 ± 11.89835.11 ± 11.065
Day 2928.25 ± 13.13135.11 ± 10.141
Day 3629.55 ± 12.16633.94 ± 10.062
Day 4326.15 ± 12.57131.11 ± 7.428
Day 5727.05 ± 10.85535.94 ± 10.804
Day 7124.53 ± 12.25928.54 ± 8.080
Day 8528.65 ± 15.72230.72 ± 15.008
Day 9231.85 ± 14.54332.43 ± 14.584
Day 11330.14 ± 14.83132.43 ± 11.092
Day 12733.92 ± 16.88238.92 ± 13.519
Day 14128.05 ± 17.08837.23 ± 15.802
Day 15528.28 ± 17.37037.83 ± 12.287
Day 16927.05 ± 17.25339.43 ± 11.174
Day 19728.95 ± 15.42931.89 ± 16.385
Day 22528.65 ± 17.25828.67 ± 7.147
Day 25326.95 ± 18.01528.17 ± 12.039
Day 28129.91 ± 18.35145.54 ± 16.168
Day 30927.17 ± 15.15236.29 ± 9.866
Day 33726.28 ± 16.73332.50 ± 10.700
Day 39328.47 ± 18.80139.79 ± 12.930
Day 44931.22 ± 18.57337.93 ± 10.547
Day 50524.89 ± 13.43544.28 ± 18.271
Day 56129.25 ± 18.66540.13 ± 11.653
Day 61732.23 ± 18.33542.78 ± 17.771
Day 67338.42 ± 13.40738.13 ± 15.418
Day 72931.28 ± 15.36634.92 ± 11.357
Day 78511.63 ± 22.69140.04 ± 26.752
Day 84124.27 ± 18.10938.54 ± 23.649
Day 89731.85 ± 17.30356.83 ± 20.035
Day 95323.93 ± 14.964—
Day 100923.99 ± 19.396—
Day 106529.07 ± 17.334—
Day 112127.27 ± 14.536—
Day 117732.28 ± 11.180—
Day 123333.08 ± 10.196—
SecondaryAbsolute Change From Baseline in Free Hemoglobin

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.

Time frame:
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
Reported as:
Mean · mg/dL
Absolute Change From Baseline in Free Hemoglobin
mg/dLCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Day 115.26 ± 36.8799.16 ± 15.310
Day 2-26.73 ± 40.706-3.94 ± 6.785
Day 8-24.03 ± 43.102-2.04 ± 6.725
Day 15-23.16 ± 41.19014.21 ± 43.762
Day 22-22.90 ± 39.726-0.66 ± 6.960
Day 29-20.03 ± 42.349-1.21 ± 8.108
Day 36-12.42 ± 47.495-2.56 ± 6.914
Day 43-13.63 ± 24.961-0.54 ± 6.546
Day 571.71 ± 14.138-1.84 ± 6.662
Day 71-17.92 ± 34.3780.18 ± 1.466
Day 85-16.80 ± 47.4071.90 ± 2.338
Day 92-25.12 ± 42.237-3.31 ± 6.295
Day 113-24.00 ± 41.08416.09 ± 42.454
Day 127-18.07 ± 52.7911.42 ± 2.945
Day 141-24.03 ± 40.625-1.52 ± 8.137
Day 155-20.58 ± 43.690-2.43 ± 8.741
Day 169-1.00 ± 91.22210.24 ± 19.275
Day 19714.93 ± 105.9583.19 ± 5.185
Day 22510.64 ± 101.86615.89 ± 32.159
Day 253-21.97 ± 40.32034.84 ± 61.838
Day 281-24.19 ± 39.910-1.36 ± 7.326
Day 309-21.57 ± 42.638-2.26 ± 9.656
Day 337-20.69 ± 42.59231.39 ± 55.947
Day 393-17.29 ± 42.263-2.11 ± 8.297
Day 449-28.60 ± 44.210-3.93 ± 7.781
Day 505-33.24 ± 41.787-1.69 ± 6.335
Day 561-34.25 ± 43.6921.59 ± 2.372
Day 617-34.68 ± 44.127-0.22 ± 6.960
Day 673-37.43 ± 54.0052.39 ± 15.832
Day 729-28.88 ± 38.550-3.99 ± 7.294
Day 785-2.55 ± 4.388-0.67 ± 3.206
Day 841-33.12 ± 43.4621.60 ± 4.485
Day 897-12.98 ± 22.2334.77 ± 5.468
Day 953-34.41 ± 46.196—
Day 10098.39 ± 135.082—
Day 1065-34.10 ± 44.867—
Day 1121-33.45 ± 43.628—
Day 1177-16.30 ± 23.441—
Day 1233-12.27 ± 20.734—
SecondaryAbsolute Change From Baseline in Reticulocytes Count

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.

Time frame:
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
Reported as:
Mean · 10^9 cells/L
Absolute Change From Baseline in Reticulocytes Count
10^9 cells/LCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Day 14.44 ± 33.2691.62 ± 22.790
Day 28.61 ± 52.3064.39 ± 31.658
Day 8-96.94 ± 69.179-104.55 ± 88.085
Day 15-130.15 ± 80.335-130.40 ± 107.295
Day 22-139.26 ± 78.206-147.70 ± 99.438
Day 29-132.28 ± 76.822-169.68 ± 129.743
Day 36-130.73 ± 72.017-167.51 ± 137.214
Day 43-129.02 ± 64.301-160.05 ± 132.859
Day 57-117.69 ± 65.394-149.53 ± 116.803
Day 71-106.83 ± 62.973-146.87 ± 129.217
Day 85-113.96 ± 65.278-167.16 ± 156.013
Day 92-110.54 ± 62.638-150.02 ± 105.893
Day 113-96.78 ± 66.366-147.06 ± 129.118
Day 127-107.84 ± 57.904-149.92 ± 115.401
Day 141-115.17 ± 70.942-108.39 ± 54.412
Day 155-99.90 ± 62.273-98.67 ± 65.700
Day 169-109.39 ± 63.159-84.57 ± 64.082
Day 197-98.87 ± 85.280-152.09 ± 137.856
Day 225-104.11 ± 72.206-143.68 ± 149.716
Day 253-104.30 ± 64.401-139.05 ± 127.212
Day 281-111.11 ± 60.896-121.06 ± 66.564
Day 309-116.88 ± 51.145-114.06 ± 77.982
Day 337-113.31 ± 61.144-170.89 ± 142.577
Day 393-58.54 ± 152.003-183.20 ± 122.298
Day 449-89.44 ± 77.782-152.66 ± 124.244
Day 505-100.68 ± 64.132-135.80 ± 117.488
Day 561-101.63 ± 67.525-163.34 ± 121.860
Day 617-101.73 ± 54.916-132.40 ± 122.940
Day 673-137.05 ± 63.373-150.14 ± 130.898
Day 729-101.16 ± 63.442-179.15 ± 131.007
Day 785-56.22 ± 26.739-134.60 ± 141.947
Day 841-103.96 ± 60.469-145.80 ± 140.363
Day 897-111.41 ± 58.641-81.27 ± 36.298
Day 953-91.00 ± 52.203—
Day 1009-110.33 ± 61.354—
Day 1065-127.35 ± 61.501—
Day 1121-115.96 ± 55.981—
Day 1177-140.14 ± 73.898—
Day 1233-123.40 ± 70.558—
SecondaryAbsolute Change From Baseline in C3 Fragment Deposition on PNH RBC

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.

Time frame:
Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233
Reported as:
Mean · percentage of PNH RBC
Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC
percentage of PNH RBCCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Day 8-5.59 ± 6.541-1.24 ± 4.510
Day 22-8.02 ± 8.198-2.35 ± 5.620
Day 29-11.64 ± 7.990-4.36 ± 2.662
Day 57-8.90 ± 5.778-5.35 ± 2.357
Day 92-8.70 ± 6.310-6.21 ± 0.866
Day 113-13.65 ± 9.927-5.10 ± 2.478
Day 141-13.18 ± 11.489-6.19 ± 4.818
Day 169-11.06 ± 5.874-4.66 ± 3.175
Day 253-10.08 ± 6.259-4.36 ± 1.538
Day 337-11.21 ± 6.118-4.08 ± 3.340
Day 505-16.04 ± 2.732-6.76 ± 2.650
Day 673-15.19 ± 2.805—
Day 785-1.00—
Day 953-15.28 ± 3.528—
Day 1121-0.94—
Day 1233-12.74—
SecondaryMean PNH Clone Size

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.

Time frame:
Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233
Reported as:
Mean · percentage of PNH RBC
Mean PNH Clone Size
percentage of PNH RBCCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Day 1 pre dose54.75 ± 32.53646.10 ± 31.436
Day 866.32 ± 29.57064.45 ± 27.711
Day 2275.23 ± 23.45879.37 ± 20.270
Day 2975.34 ± 20.83778.87 ± 17.642
Day 5785.87 ± 15.66086.45 ± 12.576
Day 9289.20 ± 16.86185.38 ± 12.939
Day 11389.28 ± 18.93686.02 ± 9.626
Day 14193.91 ± 6.10580.25 ± 6.638
Day 16987.60 ± 19.64483.69 ± 11.187
Day 25390.30 ± 18.17682.28 ± 12.649
Day 33788.69 ± 20.38191.68 ± 11.905
Day 50598.33 ± 1.73888.45 ± 10.419
Day 67397.45 ± 2.37092.48 ± 6.626
Day 78583.61 ± 9.327—
Day 95396.08 ± 3.825—
Day 112193.74 ± 7.410—
Day 123369.83 ± 43.045—
SecondaryMean Haptoglobin Levels

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.

Time frame:
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
Reported as:
Mean · g/L
Mean Haptoglobin Levels
g/LCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Day 20.55 ± 0.0710.30 ± 0.141
Day 80.70 ± 0.5480.77 ± 0.306
Day 150.93 ± 0.9600.60 ± 0.141
Day 221.18 ± 1.3870.70 ± 0.483
Day 290.94 ± 0.8960.83 ± 0.586
Day 361.08 ± 0.7790.97 ± 0.503
Day 431.26 ± 1.4010.70 ± 0.520
Day 570.63 ± 0.4161.20
Day 710.75 ± 0.4730.80
Day 850.87 ± 0.611—
Day 920.95 ± 0.4950.80
Day 1130.63 ± 0.4930.50
Day 1270.47 ± 0.208—
Day 1410.57 ± 0.3060.70
Day 1550.500.80
Day 1690.63 ± 0.5770.50
Day 1970.80 ± 0.700—
Day 2250.65 ± 0.705—
Day 2530.63 ± 0.519—
Day 2810.50 ± 0.2830.30
Day 3090.75 ± 0.0710.50
Day 3370.40—
Day 3930.60 ± 0.283—
Day 4490.200.60
Day 5050.60 ± 0.1410.60
Day 5610.600.70
Day 6170.30 ± 0.1411.90 ± 1.838
Day 6730.300.70
Day 7290.35 ± 0.0710.50
Day 7851.001.25 ± 0.919
Day 8410.47 ± 0.1530.85 ± 0.212
Day 8970.33 ± 0.058—
Day 9530.50 ± 0.141—
Day 10090.45 ± 0.071—
Day 10652.05 ± 1.768—
Day 11211.00 ± 0.935—
Day 11770.40 ± 0.000—
Day 12330.95 ± 0.636—
SecondaryAbsolute Change From Baseline in Total Bilirubin

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.

Time frame:
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
Reported as:
Mean · umol/L
Absolute Change From Baseline in Total Bilirubin
umol/LCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Day 12.94 ± 13.0381.36 ± 4.978
Day 2-21.06 ± 15.647-25.47 ± 21.598
Day 8-23.66 ± 16.081-25.97 ± 24.380
Day 15-23.86 ± 16.538-26.97 ± 24.043
Day 22-25.36 ± 15.403-25.14 ± 23.541
Day 29-24.66 ± 15.026-26.14 ± 22.345
Day 36-23.96 ± 15.945-25.31 ± 27.658
Day 43-24.66 ± 14.552-25.14 ± 23.727
Day 57-24.16 ± 13.946-22.81 ± 21.233
Day 71-23.16 ± 15.154-27.92 ± 24.924
Day 85-23.66 ± 14.595-28.42 ± 26.075
Day 92-21.66 ± 13.985-27.87 ± 25.234
Day 113-21.06 ± 15.026-26.87 ± 23.200
Day 127-22.18 ± 13.357-27.79 ± 26.965
Day 141-22.46 ± 14.404-18.23 ± 9.473
Day 155-19.73 ± 12.376-16.23 ± 9.565
Day 169-21.66 ± 13.383-14.83 ± 10.281
Day 197-24.21 ± 13.678-23.71 ± 28.849
Day 225-23.06 ± 12.410-30.06 ± 36.183
Day 253-21.36 ± 12.192-24.21 ± 30.342
Day 281-23.46 ± 12.150-16.54 ± 8.694
Day 309-22.86 ± 12.078-11.21 ± 10.635
Day 337-22.76 ± 13.248-28.71 ± 29.338
Day 393-19.73 ± 15.644-28.00 ± 27.769
Day 449-24.64 ± 13.021-23.50 ± 25.603
Day 505-27.30 ± 12.450-25.81 ± 24.978
Day 561-21.98 ± 14.718-21.10 ± 30.888
Day 617-28.85 ± 11.516-23.47 ± 21.451
Day 673-27.58 ± 13.453-24.50 ± 25.562
Day 729-23.64 ± 12.971-32.13 ± 28.799
Day 785-11.54 ± 5.370-26.67 ± 33.656
Day 841-20.49 ± 12.006-29.42 ± 32.316
Day 897-24.49 ± 13.627-16.00 ± 7.542
Day 953-23.92 ± 14.707—
Day 1009-23.92 ± 14.204—
Day 1065-25.65 ± 13.844—
Day 1121-23.35 ± 14.363—
Day 1177-29.78 ± 11.559—
Day 1233-28.78 ± 12.328—
SecondaryNumber of Participants With on Study Transfusions From Packed RBC Units

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

Time frame:
Up to 46 months
Reported as:
Count of participants · Participants
Number of Participants With on Study Transfusions From Packed RBC Units
ParticipantsCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Number of Participants With on Study Transfusions From Packed RBC Units22
SecondaryPharmacokinetics Profile: Maximum Plasma Concentration (Cmax)

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.

Time frame:
Day 1, 29, 169, 337
Reported as:
Mean · ng/mL
Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax)
ng/mLCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 25mg Bid + SoCCohort 2: LNP023 50mg Bid + SoCCohort 2: LNP023 200mg Bid + SoC
Day 13400 ± 106016101570 ± 366—
Day 293500 ± 1340—1770 ± 469—
Day 1693530 ± 853—11803130 ± 824
Day 3374030 ± 1140—24704370 ± 1790
SecondaryPharmacokinetics Profile: Area Under the Curve (AUC) Tau

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.

Time frame:
day 1, 29, 169, 337
Reported as:
Mean · h*ng/mL
Pharmacokinetics Profile: Area Under the Curve (AUC) Tau
h*ng/mLCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 25mg Bid + SoCCohort 2: LNP023 50mg Bid + SoCCohort 2: LNP023 200mg Bid + SoC
Day 118200 ± 670094708620 ± 1310—
Day 2924400 ± 8720—14800 ± 4100—
Day 16925600 ± 7570—1070023900 ± 5920
Day 33726900 ± 7640—1690037800 ± 15500
SecondaryPharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax)

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.

Time frame:
Day 1, 29, 169, 337
Reported as:
Median · hours
Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax)
hoursCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 25mg Bid + SoCCohort 2: LNP023 50mg Bid + SoCCohort 2: LNP023 200mg Bid + SoC
Day 11.50 (1.00 to 6.00)2.00 (2.00 to 2.00)2.00 (2.00 to 2.00)—
Day 292.00 (1.00 to 2.00)—2.04 (2.00 to 4.00)—
Day 1692.00 (1.00 to 4.00)—4.00 (4.00 to 4.00)2.00 (1.83 to 2.00)
Day 3372.00 (1.00 to 2.00)—2.03 (2.03 to 2.03)2.00 (1.05 to 5.00)
SecondaryRed Blood Cell Count: Mean Erythrocytes Levels

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.

Time frame:
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
Reported as:
Mean · 10^12 cells/L
Red Blood Cell Count: Mean Erythrocytes Levels
10^12 cells/LCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoC
Screening3.12 ± 0.8872.42 ± 0.427
Baseline2.73 ± 0.4662.40 ± 0.442
Day 12.67 ± 0.6152.16 ± 0.498
Day 22.70 ± 0.4852.17 ± 0.520
Day 83.17 ± 0.5853.00 ± 0.812
Day 153.43 ± 0.7233.23 ± 0.794
Day 223.58 ± 0.8353.57 ± 0.900
Day 293.72 ± 0.8573.62 ± 0.870
Day 363.75 ± 0.7533.62 ± 0.804
Day 433.67 ± 0.8073.55 ± 0.758
Day 573.69 ± 0.8523.72 ± 0.574
Day 713.50 ± 0.7873.48 ± 0.591
Day 853.65 ± 0.8413.60 ± 0.520
Day 923.76 ± 0.8283.56 ± 0.483
Day 1133.58 ± 0.8073.58 ± 0.444
Day 1273.69 ± 0.8223.75 ± 0.265
Day 1413.64 ± 0.7993.44 ± 0.493
Day 1553.53 ± 0.8153.52 ± 0.432
Day 1693.62 ± 0.8263.54 ± 0.378
Day 1973.68 ± 0.7743.77 ± 0.577
Day 2253.70 ± 0.8943.43 ± 0.513
Day 2533.62 ± 0.9303.45 ± 0.412
Day 2813.81 ± 0.8753.73 ± 0.403
Day 3093.50 ± 0.7283.58 ± 0.427
Day 3373.50 ± 0.7143.75 ± 0.580
Day 3933.63 ± 0.8764.00 ± 0.356
Day 4493.80 ± 0.9203.94 ± 0.378
Day 5053.63 ± 1.0533.92 ± 0.360
Day 5613.47 ± 0.9373.92 ± 0.370
Day 6173.80 ± 1.1493.85 ± 0.389
Day 6733.74 ± 0.7163.86 ± 0.270
Day 7293.74 ± 1.0213.93 ± 0.150
Day 7852.83 ± 0.6183.78 ± 0.263
Day 8413.64 ± 1.0813.80 ± 0.294
Day 8973.89 ± 1.1233.95 ± 0.071
Day 9533.62 ± 1.196—
Day 10093.61 ± 1.316—
Day 10653.87 ± 1.073—
Day 11213.69 ± 1.006—
Day 11774.06 ± 0.829—
Day 12334.14 ± 0.844—

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1: LNP023 200mg Bid + SoC3/10 (30%)4/10 (40%)10/10 (100%)
Cohort 2: LNP023 50mg Bid + SoC0/6 (0%)0/6 (0%)4/6 (66.7%)
Cohort 2: LNP023 200mg Bid + SoC0/5 (0%)2/5 (40%)5/5 (100%)
Total3/16 (18.8%)6/16 (37.5%)16/16 (100%)
Most frequent serious events
Most frequent serious events
EventCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg Bid + SoCCohort 2: LNP023 200mg Bid + SoCTotal
Urinary tract infectionInfections and infestations0/100/61/51/16
Bladder transitional cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/100/61/51/16
Urinary bladder polypRenal and urinary disorders0/100/61/51/16
Escherichia bacteraemiaInfections and infestations1/100/60/51/16
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/100/60/51/16
Lymphoproliferative disorderNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/100/60/51/16
Squamous cell carcinoma of the oral cavityNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/100/60/51/16
Squamous cell carcinoma of the tongueNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/100/60/51/16
Haemorrhage intracranialNervous system disorders1/100/60/51/16
Penetrating aortic ulcerVascular disorders1/100/60/51/16
Most frequent other events
Showing 10 of 102
Most frequent other events
EventCohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg Bid + SoCCohort 2: LNP023 200mg Bid + SoCTotal
ChondropathyMusculoskeletal and connective tissue disorders0/100/62/52/16
HaematuriaRenal and urinary disorders0/100/62/52/16
AstheniaGeneral disorders2/102/60/54/16
HypertriglyceridaemiaMetabolism and nutrition disorders2/102/60/54/16
HeadacheNervous system disorders2/102/61/55/16
PyrexiaGeneral disorders3/101/61/55/16
AnaemiaBlood and lymphatic system disorders2/100/61/53/16
ThrombocytopeniaBlood and lymphatic system disorders2/100/61/53/16
PalpitationsCardiac disorders0/101/61/51/16
VertigoEar and labyrinth disorders0/100/61/51/16

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Cohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoCTotal
<=18 years000
Between 18 and 65 years9615
>=65 years101
Age, Continuous
Age, Continuous(years)Cohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoCTotal
Mean44.4 ± 15.5751.7 ± 9.8347.1 ± 13.82
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoCTotal
Female336
Male7310
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Cohort 1: LNP023 200mg Bid + SoCCohort 2: LNP023 50mg/200mg Bid + SoCTotal
Unknown011
White10515
08

Study locations

3 sites
  • Novartis Investigative Site
    Paris Cedex 10, 75475, France
  • Novartis Investigative Site
    Essen, 45147, Germany
  • Novartis Investigative Site
    Napoli, 80131, Italy
09

References and documents

Publications

  • Risitano AM, Roth A, Soret J, Frieri C, de Fontbrune FS, Marano L, Alashkar F, Benajiba L, Marotta S, Rozenberg I, Milojevic J, End P, Nidamarthy PK, Junge G, Peffault de Latour R. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol. 2021 May;8(5):e344-e354. doi: 10.1016/S2352-3026(21)00028-4. Epub 2021 Mar 23. PubMed 33765419 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 12, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03439839
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Feb 20, 2018
Start date
Apr 9, 2018
Primary completion
Apr 22, 2020
Completion
Feb 28, 2022
Results posted
Jan 3, 2024
Last update
Jun 12, 2024

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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