Paroxysmal Nocturnal Hemoglobinuria (PNH) With Signs of Active Hemolysis
Conditions
Keywords
Complement, alternative pathway, paroxysmal nocturnal hemoglobinuria, hemolysis
Brief 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.
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).
Interventions
DRUGiptacopan
iptacopan bid orally administered
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No masking used in the study
Intervention model description
Open label, non-randomized study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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 × Upper limit of normal (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: Hemoglobin 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
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 Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C 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 immunosuppressive 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 corticosteroids 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 (NYHA) 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Hemoglobin | 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 | 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. |
| Absolute Change From Baseline in Free Hemoglobin | 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 | 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. |
| Absolute Change From Baseline in Reticulocytes Count | 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 | 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. |
| Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233 | 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. |
| Mean PNH Clone Size | 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. |
| Mean Haptoglobin Levels | 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. |
| Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Baseline, day 8, 15, 29, 57 and 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. |
| Number of Participants With on Study Transfusions From Packed RBC Units | Up to 46 months | Number of participants with on study transfusions from packed RBC units was collected. |
| Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 1, 29, 169, 337 | 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. |
| Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | day 1, 29, 169, 337 | 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. |
| Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | 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. |
| Red Blood Cell Count: Mean Erythrocytes Levels | 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 | 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. |
| Absolute Change From Baseline in Total Bilirubin | 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 | 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. |
Countries
France, Germany, Italy
Participant flow
Recruitment details
Participants took part in 3 investigative sites in 3 countries: France (1), Italy (1) and Germany (1).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: LNP023 200mg Bid + SoC Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC. | 10 |
| 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. | 6 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: LNP023 200mg Bid + SoC | Cohort 2: LNP023 50mg/200mg Bid + SoC | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 6 Participants | 15 Participants |
| Age, Continuous | 44.4 years STANDARD_DEVIATION 15.57 | 51.7 years STANDARD_DEVIATION 9.83 | 47.1 years STANDARD_DEVIATION 13.82 |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 10 | 0 / 6 | 0 / 5 | 3 / 16 |
| other Total, other adverse events | 10 / 10 | 4 / 6 | 5 / 5 | 16 / 16 |
| serious Total, serious adverse events | 4 / 10 | 0 / 6 | 2 / 5 | 6 / 16 |
Outcome results
Primary
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
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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Percent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92 | -53.59 Percent change from Baseline |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Percent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92 | -25.56 Percent change from Baseline |
| Total | Percent Change From Baseline in Lactate Dehydrogenase (LDH) Level at Day 92 | -43.58 Percent change from Baseline |
Secondary
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
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 673 | -15.19 percentage of PNH RBC | Standard Deviation 2.805 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 8 | -5.59 percentage of PNH RBC | Standard Deviation 6.541 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 92 | -8.70 percentage of PNH RBC | Standard Deviation 6.31 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 113 | -13.65 percentage of PNH RBC | Standard Deviation 9.927 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 141 | -13.18 percentage of PNH RBC | Standard Deviation 11.489 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 785 | -1.00 percentage of PNH RBC | — |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 953 | -15.28 percentage of PNH RBC | Standard Deviation 3.528 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 1233 | -12.74 percentage of PNH RBC | — |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 169 | -11.06 percentage of PNH RBC | Standard Deviation 5.874 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 253 | -10.08 percentage of PNH RBC | Standard Deviation 6.259 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 337 | -11.21 percentage of PNH RBC | Standard Deviation 6.118 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 505 | -16.04 percentage of PNH RBC | Standard Deviation 2.732 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 1121 | -0.94 percentage of PNH RBC | — |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 22 | -8.02 percentage of PNH RBC | Standard Deviation 8.198 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 29 | -11.64 percentage of PNH RBC | Standard Deviation 7.99 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 57 | -8.90 percentage of PNH RBC | Standard Deviation 5.778 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 8 | -1.24 percentage of PNH RBC | Standard Deviation 4.51 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 505 | -6.76 percentage of PNH RBC | Standard Deviation 2.65 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 22 | -2.35 percentage of PNH RBC | Standard Deviation 5.62 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 169 | -4.66 percentage of PNH RBC | Standard Deviation 3.175 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 29 | -4.36 percentage of PNH RBC | Standard Deviation 2.662 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 337 | -4.08 percentage of PNH RBC | Standard Deviation 3.34 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 57 | -5.35 percentage of PNH RBC | Standard Deviation 2.357 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 253 | -4.36 percentage of PNH RBC | Standard Deviation 1.538 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 92 | -6.21 percentage of PNH RBC | Standard Deviation 0.866 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 141 | -6.19 percentage of PNH RBC | Standard Deviation 4.818 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in C3 Fragment Deposition on PNH RBC | Day 113 | -5.10 percentage of PNH RBC | Standard Deviation 2.478 |
Secondary
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 43 | -13.63 mg/dL | Standard Deviation 24.961 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 57 | 1.71 mg/dL | Standard Deviation 14.138 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 127 | -18.07 mg/dL | Standard Deviation 52.791 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 141 | -24.03 mg/dL | Standard Deviation 40.625 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 169 | -1.00 mg/dL | Standard Deviation 91.222 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 505 | -33.24 mg/dL | Standard Deviation 41.787 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 561 | -34.25 mg/dL | Standard Deviation 43.692 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 617 | -34.68 mg/dL | Standard Deviation 44.127 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 673 | -37.43 mg/dL | Standard Deviation 54.005 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 729 | -28.88 mg/dL | Standard Deviation 38.55 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 785 | -2.55 mg/dL | Standard Deviation 4.388 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 841 | -33.12 mg/dL | Standard Deviation 43.462 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 897 | -12.98 mg/dL | Standard Deviation 22.233 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 953 | -34.41 mg/dL | Standard Deviation 46.196 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 1009 | 8.39 mg/dL | Standard Deviation 135.082 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 1065 | -34.10 mg/dL | Standard Deviation 44.867 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 1121 | -33.45 mg/dL | Standard Deviation 43.628 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 1177 | -16.30 mg/dL | Standard Deviation 23.441 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 1233 | -12.27 mg/dL | Standard Deviation 20.734 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 1 | 15.26 mg/dL | Standard Deviation 36.879 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 2 | -26.73 mg/dL | Standard Deviation 40.706 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 8 | -24.03 mg/dL | Standard Deviation 43.102 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 15 | -23.16 mg/dL | Standard Deviation 41.19 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 22 | -22.90 mg/dL | Standard Deviation 39.726 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 29 | -20.03 mg/dL | Standard Deviation 42.349 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 36 | -12.42 mg/dL | Standard Deviation 47.495 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 155 | -20.58 mg/dL | Standard Deviation 43.69 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 197 | 14.93 mg/dL | Standard Deviation 105.958 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 225 | 10.64 mg/dL | Standard Deviation 101.866 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 253 | -21.97 mg/dL | Standard Deviation 40.32 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 281 | -24.19 mg/dL | Standard Deviation 39.91 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 309 | -21.57 mg/dL | Standard Deviation 42.638 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 337 | -20.69 mg/dL | Standard Deviation 42.592 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 393 | -17.29 mg/dL | Standard Deviation 42.263 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 449 | -28.60 mg/dL | Standard Deviation 44.21 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 71 | -17.92 mg/dL | Standard Deviation 34.378 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 85 | -16.80 mg/dL | Standard Deviation 47.407 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 92 | -25.12 mg/dL | Standard Deviation 42.237 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 113 | -24.00 mg/dL | Standard Deviation 41.084 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 57 | -1.84 mg/dL | Standard Deviation 6.662 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 36 | -2.56 mg/dL | Standard Deviation 6.914 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 71 | 0.18 mg/dL | Standard Deviation 1.466 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 43 | -0.54 mg/dL | Standard Deviation 6.546 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 85 | 1.90 mg/dL | Standard Deviation 2.338 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 281 | -1.36 mg/dL | Standard Deviation 7.326 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 92 | -3.31 mg/dL | Standard Deviation 6.295 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 155 | -2.43 mg/dL | Standard Deviation 8.741 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 113 | 16.09 mg/dL | Standard Deviation 42.454 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 449 | -3.93 mg/dL | Standard Deviation 7.781 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 127 | 1.42 mg/dL | Standard Deviation 2.945 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 1 | 9.16 mg/dL | Standard Deviation 15.31 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 141 | -1.52 mg/dL | Standard Deviation 8.137 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 197 | 3.19 mg/dL | Standard Deviation 5.185 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 169 | 10.24 mg/dL | Standard Deviation 19.275 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 2 | -3.94 mg/dL | Standard Deviation 6.785 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 505 | -1.69 mg/dL | Standard Deviation 6.335 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 309 | -2.26 mg/dL | Standard Deviation 9.656 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 561 | 1.59 mg/dL | Standard Deviation 2.372 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 8 | -2.04 mg/dL | Standard Deviation 6.725 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 617 | -0.22 mg/dL | Standard Deviation 6.96 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 225 | 15.89 mg/dL | Standard Deviation 32.159 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 673 | 2.39 mg/dL | Standard Deviation 15.832 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 15 | 14.21 mg/dL | Standard Deviation 43.762 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 729 | -3.99 mg/dL | Standard Deviation 7.294 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 393 | -2.11 mg/dL | Standard Deviation 8.297 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 785 | -0.67 mg/dL | Standard Deviation 3.206 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 22 | -0.66 mg/dL | Standard Deviation 6.96 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 841 | 1.60 mg/dL | Standard Deviation 4.485 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 253 | 34.84 mg/dL | Standard Deviation 61.838 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 897 | 4.77 mg/dL | Standard Deviation 5.468 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 29 | -1.21 mg/dL | Standard Deviation 8.108 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Free Hemoglobin | Day 337 | 31.39 mg/dL | Standard Deviation 55.947 |
Secondary
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 281 | 29.91 g/L | Standard Deviation 18.351 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 113 | 30.14 g/L | Standard Deviation 14.831 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 127 | 33.92 g/L | Standard Deviation 16.882 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 141 | 28.05 g/L | Standard Deviation 17.088 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 729 | 31.28 g/L | Standard Deviation 15.366 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 785 | 11.63 g/L | Standard Deviation 22.691 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 841 | 24.27 g/L | Standard Deviation 18.109 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 897 | 31.85 g/L | Standard Deviation 17.303 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 953 | 23.93 g/L | Standard Deviation 14.964 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 1009 | 23.99 g/L | Standard Deviation 19.396 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 1065 | 29.07 g/L | Standard Deviation 17.334 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 1121 | 27.27 g/L | Standard Deviation 14.536 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 1177 | 32.28 g/L | Standard Deviation 11.18 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 36 | 29.55 g/L | Standard Deviation 12.166 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 8 | 12.85 g/L | Standard Deviation 9.228 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 15 | 20.25 g/L | Standard Deviation 10.122 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 22 | 24.15 g/L | Standard Deviation 11.898 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 29 | 28.25 g/L | Standard Deviation 13.131 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 43 | 26.15 g/L | Standard Deviation 12.571 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 155 | 28.28 g/L | Standard Deviation 17.37 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 169 | 27.05 g/L | Standard Deviation 17.253 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 197 | 28.95 g/L | Standard Deviation 15.429 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 225 | 28.65 g/L | Standard Deviation 17.258 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 253 | 26.95 g/L | Standard Deviation 18.015 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 1 | -4.05 g/L | Standard Deviation 8.75 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 309 | 27.17 g/L | Standard Deviation 15.152 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 337 | 26.28 g/L | Standard Deviation 16.733 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 393 | 28.47 g/L | Standard Deviation 18.801 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 449 | 31.22 g/L | Standard Deviation 18.573 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 505 | 24.89 g/L | Standard Deviation 13.435 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 561 | 29.25 g/L | Standard Deviation 18.665 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 617 | 32.23 g/L | Standard Deviation 18.335 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 673 | 38.42 g/L | Standard Deviation 13.407 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 1233 | 33.08 g/L | Standard Deviation 10.196 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 2 | -3.65 g/L | Standard Deviation 7.638 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 57 | 27.05 g/L | Standard Deviation 10.855 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 71 | 24.53 g/L | Standard Deviation 12.259 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 85 | 28.65 g/L | Standard Deviation 15.722 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 92 | 31.85 g/L | Standard Deviation 14.543 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 1 | -6.67 g/L | Standard Deviation 7.218 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 8 | 20.11 g/L | Standard Deviation 13.475 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 43 | 31.11 g/L | Standard Deviation 7.428 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 449 | 37.93 g/L | Standard Deviation 10.547 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 57 | 35.94 g/L | Standard Deviation 10.804 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 15 | 26.44 g/L | Standard Deviation 10.047 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 71 | 28.54 g/L | Standard Deviation 8.08 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 281 | 45.54 g/L | Standard Deviation 16.168 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 85 | 30.72 g/L | Standard Deviation 15.008 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 22 | 35.11 g/L | Standard Deviation 11.065 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 92 | 32.43 g/L | Standard Deviation 14.584 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 673 | 38.13 g/L | Standard Deviation 15.418 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 113 | 32.43 g/L | Standard Deviation 11.092 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 36 | 33.94 g/L | Standard Deviation 10.062 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 127 | 38.92 g/L | Standard Deviation 13.519 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 309 | 36.29 g/L | Standard Deviation 9.866 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 141 | 37.23 g/L | Standard Deviation 15.802 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 729 | 34.92 g/L | Standard Deviation 11.357 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 505 | 44.28 g/L | Standard Deviation 18.271 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 785 | 40.04 g/L | Standard Deviation 26.752 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 155 | 37.83 g/L | Standard Deviation 12.287 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 841 | 38.54 g/L | Standard Deviation 23.649 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 337 | 32.50 g/L | Standard Deviation 10.7 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 897 | 56.83 g/L | Standard Deviation 20.035 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 169 | 39.43 g/L | Standard Deviation 11.174 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 617 | 42.78 g/L | Standard Deviation 17.771 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 197 | 31.89 g/L | Standard Deviation 16.385 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 393 | 39.79 g/L | Standard Deviation 12.93 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 225 | 28.67 g/L | Standard Deviation 7.147 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 561 | 40.13 g/L | Standard Deviation 11.653 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 29 | 35.11 g/L | Standard Deviation 10.141 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 2 | -8.06 g/L | Standard Deviation 6.83 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Hemoglobin | Day 253 | 28.17 g/L | Standard Deviation 12.039 |
Secondary
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
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
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 57 | -317.07 U/L |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 29 | -368.17 U/L |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 8 | -272.57 U/L |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 92 | -330.52 U/L |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 15 | -353.97 U/L |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 15 | -175.07 U/L |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 8 | -145.22 U/L |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 29 | -191.22 U/L |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 57 | -135.89 U/L |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 92 | -109.07 U/L |
| Total | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 92 | -251.43 U/L |
| Total | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 57 | -249.13 U/L |
| Total | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 8 | -224.81 U/L |
| Total | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 29 | -301.81 U/L |
| Total | Absolute Change From Baseline in Lactate Dehydrogenase (LDH) Level | Day 15 | -294.33 U/L |
Secondary
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
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 225 | -104.11 10^9 cells/L | Standard Deviation 72.206 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 36 | -130.73 10^9 cells/L | Standard Deviation 72.017 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 43 | -129.02 10^9 cells/L | Standard Deviation 64.301 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 57 | -117.69 10^9 cells/L | Standard Deviation 65.394 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 71 | -106.83 10^9 cells/L | Standard Deviation 62.973 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 85 | -113.96 10^9 cells/L | Standard Deviation 65.278 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 92 | -110.54 10^9 cells/L | Standard Deviation 62.638 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 673 | -137.05 10^9 cells/L | Standard Deviation 63.373 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 729 | -101.16 10^9 cells/L | Standard Deviation 63.442 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 785 | -56.22 10^9 cells/L | Standard Deviation 26.739 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 841 | -103.96 10^9 cells/L | Standard Deviation 60.469 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 897 | -111.41 10^9 cells/L | Standard Deviation 58.641 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 953 | -91.00 10^9 cells/L | Standard Deviation 52.203 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 1009 | -110.33 10^9 cells/L | Standard Deviation 61.354 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 1065 | -127.35 10^9 cells/L | Standard Deviation 61.501 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 1121 | -115.96 10^9 cells/L | Standard Deviation 55.981 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 1177 | -140.14 10^9 cells/L | Standard Deviation 73.898 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 1233 | -123.40 10^9 cells/L | Standard Deviation 70.558 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 113 | -96.78 10^9 cells/L | Standard Deviation 66.366 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 127 | -107.84 10^9 cells/L | Standard Deviation 57.904 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 141 | -115.17 10^9 cells/L | Standard Deviation 70.942 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 155 | -99.90 10^9 cells/L | Standard Deviation 62.273 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 169 | -109.39 10^9 cells/L | Standard Deviation 63.159 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 197 | -98.87 10^9 cells/L | Standard Deviation 85.28 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 1 | 4.44 10^9 cells/L | Standard Deviation 33.269 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 253 | -104.30 10^9 cells/L | Standard Deviation 64.401 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 281 | -111.11 10^9 cells/L | Standard Deviation 60.896 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 309 | -116.88 10^9 cells/L | Standard Deviation 51.145 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 337 | -113.31 10^9 cells/L | Standard Deviation 61.144 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 393 | -58.54 10^9 cells/L | Standard Deviation 152.003 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 561 | -101.63 10^9 cells/L | Standard Deviation 67.525 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 449 | -89.44 10^9 cells/L | Standard Deviation 77.782 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 505 | -100.68 10^9 cells/L | Standard Deviation 64.132 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 617 | -101.73 10^9 cells/L | Standard Deviation 54.916 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 2 | 8.61 10^9 cells/L | Standard Deviation 52.306 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 8 | -96.94 10^9 cells/L | Standard Deviation 69.179 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 15 | -130.15 10^9 cells/L | Standard Deviation 80.335 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 22 | -139.26 10^9 cells/L | Standard Deviation 78.206 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 29 | -132.28 10^9 cells/L | Standard Deviation 76.822 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 1 | 1.62 10^9 cells/L | Standard Deviation 22.79 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 337 | -170.89 10^9 cells/L | Standard Deviation 142.577 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 2 | 4.39 10^9 cells/L | Standard Deviation 31.658 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 197 | -152.09 10^9 cells/L | Standard Deviation 137.856 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 8 | -104.55 10^9 cells/L | Standard Deviation 88.085 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 617 | -132.40 10^9 cells/L | Standard Deviation 122.94 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 15 | -130.40 10^9 cells/L | Standard Deviation 107.295 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 393 | -183.20 10^9 cells/L | Standard Deviation 122.298 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 22 | -147.70 10^9 cells/L | Standard Deviation 99.438 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 253 | -139.05 10^9 cells/L | Standard Deviation 127.212 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 29 | -169.68 10^9 cells/L | Standard Deviation 129.743 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 225 | -143.68 10^9 cells/L | Standard Deviation 149.716 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 36 | -167.51 10^9 cells/L | Standard Deviation 137.214 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 92 | -150.02 10^9 cells/L | Standard Deviation 105.893 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 43 | -160.05 10^9 cells/L | Standard Deviation 132.859 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 505 | -135.80 10^9 cells/L | Standard Deviation 117.488 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 57 | -149.53 10^9 cells/L | Standard Deviation 116.803 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 113 | -147.06 10^9 cells/L | Standard Deviation 129.118 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 71 | -146.87 10^9 cells/L | Standard Deviation 129.217 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 281 | -121.06 10^9 cells/L | Standard Deviation 66.564 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 85 | -167.16 10^9 cells/L | Standard Deviation 156.013 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 127 | -149.92 10^9 cells/L | Standard Deviation 115.401 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 561 | -163.34 10^9 cells/L | Standard Deviation 121.86 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 673 | -150.14 10^9 cells/L | Standard Deviation 130.898 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 141 | -108.39 10^9 cells/L | Standard Deviation 54.412 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 729 | -179.15 10^9 cells/L | Standard Deviation 131.007 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 309 | -114.06 10^9 cells/L | Standard Deviation 77.982 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 785 | -134.60 10^9 cells/L | Standard Deviation 141.947 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 155 | -98.67 10^9 cells/L | Standard Deviation 65.7 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 841 | -145.80 10^9 cells/L | Standard Deviation 140.363 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 449 | -152.66 10^9 cells/L | Standard Deviation 124.244 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 897 | -81.27 10^9 cells/L | Standard Deviation 36.298 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Reticulocytes Count | Day 169 | -84.57 10^9 cells/L | Standard Deviation 64.082 |
Secondary
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 113 | -21.06 umol/L | Standard Deviation 15.026 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 43 | -24.66 umol/L | Standard Deviation 14.552 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 57 | -24.16 umol/L | Standard Deviation 13.946 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 71 | -23.16 umol/L | Standard Deviation 15.154 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 85 | -23.66 umol/L | Standard Deviation 14.595 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 197 | -24.21 umol/L | Standard Deviation 13.678 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 225 | -23.06 umol/L | Standard Deviation 12.41 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 253 | -21.36 umol/L | Standard Deviation 12.192 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 309 | -22.86 umol/L | Standard Deviation 12.078 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 337 | -22.76 umol/L | Standard Deviation 13.248 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 393 | -19.73 umol/L | Standard Deviation 15.644 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 449 | -24.64 umol/L | Standard Deviation 13.021 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 505 | -27.30 umol/L | Standard Deviation 12.45 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 561 | -21.98 umol/L | Standard Deviation 14.718 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 617 | -28.85 umol/L | Standard Deviation 11.516 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 673 | -27.58 umol/L | Standard Deviation 13.453 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 729 | -23.64 umol/L | Standard Deviation 12.971 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 785 | -11.54 umol/L | Standard Deviation 5.37 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 841 | -20.49 umol/L | Standard Deviation 12.006 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 1 | 2.94 umol/L | Standard Deviation 13.038 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 2 | -21.06 umol/L | Standard Deviation 15.647 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 92 | -21.66 umol/L | Standard Deviation 13.985 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 8 | -23.66 umol/L | Standard Deviation 16.081 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 127 | -22.18 umol/L | Standard Deviation 13.357 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 141 | -22.46 umol/L | Standard Deviation 14.404 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 155 | -19.73 umol/L | Standard Deviation 12.376 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 169 | -21.66 umol/L | Standard Deviation 13.383 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 897 | -24.49 umol/L | Standard Deviation 13.627 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 953 | -23.92 umol/L | Standard Deviation 14.707 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 1009 | -23.92 umol/L | Standard Deviation 14.204 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 1065 | -25.65 umol/L | Standard Deviation 13.844 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 1121 | -23.35 umol/L | Standard Deviation 14.363 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 1177 | -29.78 umol/L | Standard Deviation 11.559 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 1233 | -28.78 umol/L | Standard Deviation 12.328 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 15 | -23.86 umol/L | Standard Deviation 16.538 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 22 | -25.36 umol/L | Standard Deviation 15.403 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 29 | -24.66 umol/L | Standard Deviation 15.026 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 281 | -23.46 umol/L | Standard Deviation 12.15 |
| Cohort 1: LNP023 200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 36 | -23.96 umol/L | Standard Deviation 15.945 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 8 | -25.97 umol/L | Standard Deviation 24.38 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 505 | -25.81 umol/L | Standard Deviation 24.978 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 15 | -26.97 umol/L | Standard Deviation 24.043 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 841 | -29.42 umol/L | Standard Deviation 32.316 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 22 | -25.14 umol/L | Standard Deviation 23.541 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 561 | -21.10 umol/L | Standard Deviation 30.888 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 29 | -26.14 umol/L | Standard Deviation 22.345 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 92 | -27.87 umol/L | Standard Deviation 25.234 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 617 | -23.47 umol/L | Standard Deviation 21.451 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 36 | -25.31 umol/L | Standard Deviation 27.658 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 155 | -16.23 umol/L | Standard Deviation 9.565 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 43 | -25.14 umol/L | Standard Deviation 23.727 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 673 | -24.50 umol/L | Standard Deviation 25.562 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 57 | -22.81 umol/L | Standard Deviation 21.233 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 113 | -26.87 umol/L | Standard Deviation 23.2 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 71 | -27.92 umol/L | Standard Deviation 24.924 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 729 | -32.13 umol/L | Standard Deviation 28.799 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 897 | -16.00 umol/L | Standard Deviation 7.542 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 197 | -23.71 umol/L | Standard Deviation 28.849 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 785 | -26.67 umol/L | Standard Deviation 33.656 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 225 | -30.06 umol/L | Standard Deviation 36.183 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 127 | -27.79 umol/L | Standard Deviation 26.965 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 253 | -24.21 umol/L | Standard Deviation 30.342 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 281 | -16.54 umol/L | Standard Deviation 8.694 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 169 | -14.83 umol/L | Standard Deviation 10.281 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 309 | -11.21 umol/L | Standard Deviation 10.635 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 1 | 1.36 umol/L | Standard Deviation 4.978 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 337 | -28.71 umol/L | Standard Deviation 29.338 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 141 | -18.23 umol/L | Standard Deviation 9.473 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 393 | -28.00 umol/L | Standard Deviation 27.769 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 2 | -25.47 umol/L | Standard Deviation 21.598 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 449 | -23.50 umol/L | Standard Deviation 25.603 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Absolute Change From Baseline in Total Bilirubin | Day 85 | -28.42 umol/L | Standard Deviation 26.075 |
Secondary
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
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 haptoglobin value for that particular visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 29 | 0.94 g/L | Standard Deviation 0.896 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 309 | 0.75 g/L | Standard Deviation 0.071 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 337 | 0.40 g/L | — |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 393 | 0.60 g/L | Standard Deviation 0.283 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 449 | 0.20 g/L | — |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 505 | 0.60 g/L | Standard Deviation 0.141 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 561 | 0.60 g/L | — |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 617 | 0.30 g/L | Standard Deviation 0.141 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 673 | 0.30 g/L | — |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 729 | 0.35 g/L | Standard Deviation 0.071 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 785 | 1.00 g/L | — |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 841 | 0.47 g/L | Standard Deviation 0.153 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 15 | 0.93 g/L | Standard Deviation 0.96 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 22 | 1.18 g/L | Standard Deviation 1.387 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 2 | 0.55 g/L | Standard Deviation 0.071 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 36 | 1.08 g/L | Standard Deviation 0.779 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 43 | 1.26 g/L | Standard Deviation 1.401 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 57 | 0.63 g/L | Standard Deviation 0.416 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 897 | 0.33 g/L | Standard Deviation 0.058 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 953 | 0.50 g/L | Standard Deviation 0.141 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 1009 | 0.45 g/L | Standard Deviation 0.071 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 1065 | 2.05 g/L | Standard Deviation 1.768 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 1121 | 1.00 g/L | Standard Deviation 0.935 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 1177 | 0.40 g/L | Standard Deviation 0 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 1233 | 0.95 g/L | Standard Deviation 0.636 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 8 | 0.70 g/L | Standard Deviation 0.548 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 71 | 0.75 g/L | Standard Deviation 0.473 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 85 | 0.87 g/L | Standard Deviation 0.611 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 92 | 0.95 g/L | Standard Deviation 0.495 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 113 | 0.63 g/L | Standard Deviation 0.493 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 127 | 0.47 g/L | Standard Deviation 0.208 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 141 | 0.57 g/L | Standard Deviation 0.306 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 155 | 0.50 g/L | — |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 169 | 0.63 g/L | Standard Deviation 0.577 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 197 | 0.80 g/L | Standard Deviation 0.7 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 225 | 0.65 g/L | Standard Deviation 0.705 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 253 | 0.63 g/L | Standard Deviation 0.519 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean Haptoglobin Levels | Day 281 | 0.50 g/L | Standard Deviation 0.283 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 2 | 0.30 g/L | Standard Deviation 0.141 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 309 | 0.50 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 8 | 0.77 g/L | Standard Deviation 0.306 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 57 | 1.20 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 729 | 0.50 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 71 | 0.80 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 841 | 0.85 g/L | Standard Deviation 0.212 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 785 | 1.25 g/L | Standard Deviation 0.919 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 92 | 0.80 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 449 | 0.60 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 113 | 0.50 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 29 | 0.83 g/L | Standard Deviation 0.586 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 505 | 0.60 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 141 | 0.70 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 43 | 0.70 g/L | Standard Deviation 0.52 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 155 | 0.80 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 561 | 0.70 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 169 | 0.50 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 15 | 0.60 g/L | Standard Deviation 0.141 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 617 | 1.90 g/L | Standard Deviation 1.838 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 36 | 0.97 g/L | Standard Deviation 0.503 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 673 | 0.70 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 281 | 0.30 g/L | — |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean Haptoglobin Levels | Day 22 | 0.70 g/L | Standard Deviation 0.483 |
Secondary
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
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 clone size value for that particular visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 1233 | 69.83 percentage of PNH RBC | Standard Deviation 43.045 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 113 | 89.28 percentage of PNH RBC | Standard Deviation 18.936 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 673 | 97.45 percentage of PNH RBC | Standard Deviation 2.37 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 141 | 93.91 percentage of PNH RBC | Standard Deviation 6.105 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 8 | 66.32 percentage of PNH RBC | Standard Deviation 29.57 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 169 | 87.60 percentage of PNH RBC | Standard Deviation 19.644 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 785 | 83.61 percentage of PNH RBC | Standard Deviation 9.327 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 253 | 90.30 percentage of PNH RBC | Standard Deviation 18.176 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 22 | 75.23 percentage of PNH RBC | Standard Deviation 23.458 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 337 | 88.69 percentage of PNH RBC | Standard Deviation 20.381 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 953 | 96.08 percentage of PNH RBC | Standard Deviation 3.825 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 505 | 98.33 percentage of PNH RBC | Standard Deviation 1.738 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 1 pre dose | 54.75 percentage of PNH RBC | Standard Deviation 32.536 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 29 | 75.34 percentage of PNH RBC | Standard Deviation 20.837 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 57 | 85.87 percentage of PNH RBC | Standard Deviation 15.66 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 1121 | 93.74 percentage of PNH RBC | Standard Deviation 7.41 |
| Cohort 1: LNP023 200mg Bid + SoC | Mean PNH Clone Size | Day 92 | 89.20 percentage of PNH RBC | Standard Deviation 16.861 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 505 | 88.45 percentage of PNH RBC | Standard Deviation 10.419 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 1 pre dose | 46.10 percentage of PNH RBC | Standard Deviation 31.436 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 673 | 92.48 percentage of PNH RBC | Standard Deviation 6.626 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 29 | 78.87 percentage of PNH RBC | Standard Deviation 17.642 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 8 | 64.45 percentage of PNH RBC | Standard Deviation 27.711 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 22 | 79.37 percentage of PNH RBC | Standard Deviation 20.27 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 57 | 86.45 percentage of PNH RBC | Standard Deviation 12.576 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 92 | 85.38 percentage of PNH RBC | Standard Deviation 12.939 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 113 | 86.02 percentage of PNH RBC | Standard Deviation 9.626 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 141 | 80.25 percentage of PNH RBC | Standard Deviation 6.638 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 169 | 83.69 percentage of PNH RBC | Standard Deviation 11.187 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 253 | 82.28 percentage of PNH RBC | Standard Deviation 12.649 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Mean PNH Clone Size | Day 337 | 91.68 percentage of PNH RBC | Standard Deviation 11.905 |
Secondary
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
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Number of Participants With on Study Transfusions From Packed RBC Units | 2 Participants |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Number of Participants With on Study Transfusions From Packed RBC Units | 2 Participants |
Secondary
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 1 | 18200 h*ng/mL | Standard Deviation 6700 |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 29 | 24400 h*ng/mL | Standard Deviation 8720 |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 169 | 25600 h*ng/mL | Standard Deviation 7570 |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 337 | 26900 h*ng/mL | Standard Deviation 7640 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 1 | 9470 h*ng/mL | — |
| Total | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 1 | 8620 h*ng/mL | Standard Deviation 1310 |
| Total | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 337 | 16900 h*ng/mL | — |
| Total | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 169 | 10700 h*ng/mL | — |
| Total | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 29 | 14800 h*ng/mL | Standard Deviation 4100 |
| Cohort 2: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 169 | 23900 h*ng/mL | Standard Deviation 5920 |
| Cohort 2: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Area Under the Curve (AUC) Tau | Day 337 | 37800 h*ng/mL | Standard Deviation 15500 |
Secondary
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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 337 | 4030 ng/mL | Standard Deviation 1140 |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 29 | 3500 ng/mL | Standard Deviation 1340 |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 169 | 3530 ng/mL | Standard Deviation 853 |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 1 | 3400 ng/mL | Standard Deviation 1060 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 1 | 1610 ng/mL | — |
| Total | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 169 | 1180 ng/mL | — |
| Total | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 337 | 2470 ng/mL | — |
| Total | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 1 | 1570 ng/mL | Standard Deviation 366 |
| Total | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 29 | 1770 ng/mL | Standard Deviation 469 |
| Cohort 2: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 337 | 4370 ng/mL | Standard Deviation 1790 |
| Cohort 2: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Day 169 | 3130 ng/mL | Standard Deviation 824 |
Secondary
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
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 Tmax value for that particular visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 1 | 1.50 hours |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 29 | 2.00 hours |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 169 | 2.00 hours |
| Cohort 1: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 337 | 2.00 hours |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 1 | 2.00 hours |
| Total | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 1 | 2.00 hours |
| Total | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 337 | 2.03 hours |
| Total | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 169 | 4.00 hours |
| Total | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 29 | 2.04 hours |
| Cohort 2: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 169 | 2.00 hours |
| Cohort 2: LNP023 200mg Bid + SoC | Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax) | Day 337 | 2.00 hours |
Secondary
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
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 71 | 3.50 10^12 cells/L | Standard Deviation 0.787 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 281 | 3.81 10^12 cells/L | Standard Deviation 0.875 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 22 | 3.58 10^12 cells/L | Standard Deviation 0.835 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 309 | 3.50 10^12 cells/L | Standard Deviation 0.728 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 85 | 3.65 10^12 cells/L | Standard Deviation 0.841 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 337 | 3.50 10^12 cells/L | Standard Deviation 0.714 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Screening | 3.12 10^12 cells/L | Standard Deviation 0.887 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 393 | 3.63 10^12 cells/L | Standard Deviation 0.876 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 92 | 3.76 10^12 cells/L | Standard Deviation 0.828 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 449 | 3.80 10^12 cells/L | Standard Deviation 0.92 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 29 | 3.72 10^12 cells/L | Standard Deviation 0.857 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 505 | 3.63 10^12 cells/L | Standard Deviation 1.053 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 113 | 3.58 10^12 cells/L | Standard Deviation 0.807 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 561 | 3.47 10^12 cells/L | Standard Deviation 0.937 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 8 | 3.17 10^12 cells/L | Standard Deviation 0.585 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 617 | 3.80 10^12 cells/L | Standard Deviation 1.149 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 127 | 3.69 10^12 cells/L | Standard Deviation 0.822 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 673 | 3.74 10^12 cells/L | Standard Deviation 0.716 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 36 | 3.75 10^12 cells/L | Standard Deviation 0.753 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 729 | 3.74 10^12 cells/L | Standard Deviation 1.021 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 141 | 3.64 10^12 cells/L | Standard Deviation 0.799 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 785 | 2.83 10^12 cells/L | Standard Deviation 0.618 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Baseline | 2.73 10^12 cells/L | Standard Deviation 0.466 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 841 | 3.64 10^12 cells/L | Standard Deviation 1.081 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 155 | 3.53 10^12 cells/L | Standard Deviation 0.815 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 897 | 3.89 10^12 cells/L | Standard Deviation 1.123 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 43 | 3.67 10^12 cells/L | Standard Deviation 0.807 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 953 | 3.62 10^12 cells/L | Standard Deviation 1.196 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 1009 | 3.61 10^12 cells/L | Standard Deviation 1.316 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 1065 | 3.87 10^12 cells/L | Standard Deviation 1.073 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 1121 | 3.69 10^12 cells/L | Standard Deviation 1.006 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 1177 | 4.06 10^12 cells/L | Standard Deviation 0.829 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 1233 | 4.14 10^12 cells/L | Standard Deviation 0.844 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 1 | 2.67 10^12 cells/L | Standard Deviation 0.615 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 169 | 3.62 10^12 cells/L | Standard Deviation 0.826 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 15 | 3.43 10^12 cells/L | Standard Deviation 0.723 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 197 | 3.68 10^12 cells/L | Standard Deviation 0.774 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 57 | 3.69 10^12 cells/L | Standard Deviation 0.852 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 225 | 3.70 10^12 cells/L | Standard Deviation 0.894 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 2 | 2.70 10^12 cells/L | Standard Deviation 0.485 |
| Cohort 1: LNP023 200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 253 | 3.62 10^12 cells/L | Standard Deviation 0.93 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 1 | 2.16 10^12 cells/L | Standard Deviation 0.498 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Screening | 2.42 10^12 cells/L | Standard Deviation 0.427 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 2 | 2.17 10^12 cells/L | Standard Deviation 0.52 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 8 | 3.00 10^12 cells/L | Standard Deviation 0.812 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 15 | 3.23 10^12 cells/L | Standard Deviation 0.794 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 22 | 3.57 10^12 cells/L | Standard Deviation 0.9 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 29 | 3.62 10^12 cells/L | Standard Deviation 0.87 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 36 | 3.62 10^12 cells/L | Standard Deviation 0.804 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 43 | 3.55 10^12 cells/L | Standard Deviation 0.758 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 57 | 3.72 10^12 cells/L | Standard Deviation 0.574 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 71 | 3.48 10^12 cells/L | Standard Deviation 0.591 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 85 | 3.60 10^12 cells/L | Standard Deviation 0.52 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 92 | 3.56 10^12 cells/L | Standard Deviation 0.483 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 113 | 3.58 10^12 cells/L | Standard Deviation 0.444 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 127 | 3.75 10^12 cells/L | Standard Deviation 0.265 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 141 | 3.44 10^12 cells/L | Standard Deviation 0.493 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 155 | 3.52 10^12 cells/L | Standard Deviation 0.432 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 169 | 3.54 10^12 cells/L | Standard Deviation 0.378 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 197 | 3.77 10^12 cells/L | Standard Deviation 0.577 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 225 | 3.43 10^12 cells/L | Standard Deviation 0.513 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 253 | 3.45 10^12 cells/L | Standard Deviation 0.412 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 281 | 3.73 10^12 cells/L | Standard Deviation 0.403 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 309 | 3.58 10^12 cells/L | Standard Deviation 0.427 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 337 | 3.75 10^12 cells/L | Standard Deviation 0.58 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 393 | 4.00 10^12 cells/L | Standard Deviation 0.356 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 449 | 3.94 10^12 cells/L | Standard Deviation 0.378 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 505 | 3.92 10^12 cells/L | Standard Deviation 0.36 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 561 | 3.92 10^12 cells/L | Standard Deviation 0.37 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 617 | 3.85 10^12 cells/L | Standard Deviation 0.389 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 673 | 3.86 10^12 cells/L | Standard Deviation 0.27 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 729 | 3.93 10^12 cells/L | Standard Deviation 0.15 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 785 | 3.78 10^12 cells/L | Standard Deviation 0.263 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 841 | 3.80 10^12 cells/L | Standard Deviation 0.294 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Day 897 | 3.95 10^12 cells/L | Standard Deviation 0.071 |
| Cohort 2: LNP023 50mg/200mg Bid + SoC | Red Blood Cell Count: Mean Erythrocytes Levels | Baseline | 2.40 10^12 cells/L | Standard Deviation 0.442 |