Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2017-000888-33 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: LNP023 200mg bid + SoC | Experimental | Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 |
|
| Cohort 2: LNP023 50mg/200mg bid + SoC | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| iptacopan | Drug | iptacopan bid orally administered |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Day 92 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Paris | 75475 | France | |||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33765419 | Result | Risitano AM, Roth A, Soret J, Frieri C, de Fontbrune FS, Marano L, Alashkar F, Benajiba L, Marotta S, Rozenberg I, Milojevic J, End P, Nidamarthy PK, Junge G, Peffault de Latour R. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol. 2021 May;8(5):e344-e354. doi: 10.1016/S2352-3026(21)00028-4. Epub 2021 Mar 23. |
| Label | URL |
|---|---|
| Patient Lay Trial Summary | View source |
Not provided
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Not provided
Not provided
Not provided
Not provided
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 took part in 3 investigative sites in 3 countries: France (1), Italy (1) and Germany (1).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: LNP023 200mg Bid + SoC | Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 26, 2021 | Feb 17, 2023 |
Not provided
Open label, non-randomized study
Not provided
Not provided
No masking used in the study
Not provided
| Standard of Care | Combination Product | 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. |
|
| Baseline, day 8, 15, 29, 57 and 92 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 | 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. | Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233 |
| 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. | 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 |
| 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. | 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 |
| Number of Participants With on Study Transfusions From Packed RBC Units | Number of participants with on study transfusions from packed RBC units was collected. | Up to 46 months |
| 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. | Day 1, 29, 169, 337 |
| 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. | day 1, 29, 169, 337 |
| 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. | Day 1, 29, 169, 337 |
| 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. | 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 |
| Essen |
| 45147 |
| Germany |
| Novartis Investigative Site | Naples | 80131 | Italy |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: LNP023 200mg Bid + SoC | Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | 90% Confidence Interval | Percent change from Baseline | Baseline and Day 92 |
|
|
| |||||||||||||||||||||||||||||||
| 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. | 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 | Posted | Mean | 90% Confidence Interval | U/L | Baseline, day 8, 15, 29, 57 and 92 |
| |||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | g/L | 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 |
| |||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | mg/dL | 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 |
| |||||||||||||||||||||||||||||||||
| 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. | 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 | Posted | Mean | Standard Deviation | 10^9 cells/L | 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 |
| |||||||||||||||||||||||||||||||||
| 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. | 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 | Posted | Mean | Standard Deviation | percentage of PNH RBC | Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233 |
| |||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | percentage of PNH RBC | Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233 |
|
| ||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | g/L | 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 |
|
| ||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | umol/L | 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 |
| |||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Count of Participants | Participants | Up to 46 months |
|
| |||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Day 1, 29, 169, 337 |
| |||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | h*ng/mL | day 1, 29, 169, 337 |
| |||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Median | Full Range | hours | Day 1, 29, 169, 337 |
| |||||||||||||||||||||||||||||||||
| 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. | 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 | Posted | Mean | Standard Deviation | 10^12 cells/L | 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 |
|
|
Adverse events were reported from first dose of study treatment until end of study treatment plus 14 days post treatment, up to a maximum duration of 187 weeks. Serious adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: LNP023 200mg Bid + SoC | Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC. | 3 | 10 | 4 | 10 | 10 | 10 |
| EG001 | Cohort 2: LNP023 50mg Bid + SoC | Orally administered iptacopan 50 mg b.i.d. in Part 1 and iptacopan 50 mg b.i.d. or 200 mg b.i.d. in Part 2 in addition to SoC. This arm summarizes all events that started when treated with iptacopan 50 mg b.i.d. in Cophort 2 | 0 | 6 | 0 | 6 | 4 | 6 |
| EG002 | Cohort 2: LNP023 200mg Bid + SoC | Orally administered iptacopan 50 mg b.i.d. in Part 1 and iptacopan 50 mg b.i.d. or 200 mg b.i.d. in Part 2 in addition to SoC. This arm summarizes all events that started when treated with iptacopan 200 mg b.i.d. in Cohort 2. Total number at risk only includes patients who received LNP023 200mg bid. | 0 | 5 | 2 | 5 | 5 | 5 |
| EG003 | Total | Total | 3 | 16 | 6 | 16 | 16 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Escherichia bacteraemia | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
| |
| Bladder transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
| |
| Lymphoproliferative disorder | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
| |
| Squamous cell carcinoma of the oral cavity | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
| |
| Squamous cell carcinoma of the tongue | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Urinary bladder polyp | Renal and urinary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Penetrating aortic ulcer | Vascular disorders | MedDRA (24.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Tongue ulceration | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Medical device site irritation | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Medical device site pain | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hepatic cytolysis | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Ocular icterus | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Vaginal infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
| |
| Traumatic haematoma | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
| |
| Vaccination complication | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| SARS-CoV-2 test negative | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hyperferritinaemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Chondropathy | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Angiofibroma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
| |
| Ageusia | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Anosmia | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Cervical radiculopathy | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Alcohol abuse | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Nightmare | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Poor quality sleep | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Nocturia | Renal and urinary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Urinary bladder polyp | Renal and urinary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Genital discomfort | Reproductive system and breast disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Haematospermia | Reproductive system and breast disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Andropause | Social circumstances | MedDRA (24.1) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (24.1) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | + 1 862 778 8300 | Novartis.email@Novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 19, 2022 | Feb 17, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006457 | Hemoglobinuria, Paroxysmal |
| D006461 | Hemolysis |
| ID | Term |
|---|---|
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009190 | Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000730766 | iptacopan |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| White |
|
Participants from Cohort 1 and Cohort 2
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Participants |
|
|
| Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
| OG002 | Cohort 2: LNP023 50mg Bid + SoC | Orally administered iptacopan 50 mg b.i.d. at the respective visit |
| OG003 | Cohort 2: LNP023 200mg Bid + SoC | Orally administered iptacopan 200 mg b.i.d. at the respective visit |
|
|
Orally administered iptacopan 50 mg b.i.d. at the respective visit |
| OG003 | Cohort 2: LNP023 200mg Bid + SoC | Orally administered iptacopan 200 mg b.i.d. at the respective visit |
|
|
Orally administered iptacopan 50 mg b.i.d. at the respective visit |
| OG003 | Cohort 2: LNP023 200mg Bid + SoC | Orally administered iptacopan 200 mg b.i.d. at the respective visit |
|
|
| Participants |
|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|