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This was a Phase II randomized, open-label, multicenter, efficacy, safety, pharmacokinetic and pharmacodynamic study assessing four iptacopan doses in adult Paroxysmal nocturnal hemoglobinuria (PNH) patients with active hemolysis who were not on eculizumab or any other complement inhibitor less than 3 months prior to first iptacopan dose. Active hemolysis was defined by a lactate dehydrogenase (LDH) value ≥ 1.5 × ULN.
LNP023 is a novel oral small molecular weight compound, that inhibits alternative complement pathway (AP). Blockade of the AP with oral LNP023 has the potential to prevent both intra - and extravascular hemolysis.
The total study duration from Screening until end of study (EOS) was approximately 28 months. This three-period study included:
Patients were randomized to Sequence 1 or Sequence 2 in a 1:1 ratio. Sequence 1: Four weeks of treatment with iptacopan 25 mg bid (Twice daily) in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. If during Period 1, LDH was not reduced by ≥ 40% from the mean of pretreatment values by Week 2 (Day 15 study visit), the iptacopan dose was to be up-titrated to 100 mg bid (starting from Study Day 17). If LDH was not reduced by ≥ 40% from the mean of pretreatment values at Week 4 (Day 29), the iptacopan dose was to be up-titrated to 200 mg bid in Period 2 and Period 3 (starting from Study Day 30). In the approximate 2-year treatment extension (Period 3), patients maintained the same treatment regimen as used in Period 2.
Sequence 2: Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3. If during Period 1, LDH was not reduced by ≥ 40% from the mean of pretreatment values by Week 2 (Day 15 study visit), the iptacopan dose was to be up-titrated to 200 mg bid (starting from Study Day 17). In the approximate 2-year treatment extension (Extension Period 3), patients remained on 200 mg bid. No further up-titration was possible
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LNP023 25 mg bid/100 mg bid | Experimental | Four weeks of treatment with iptacopan 25 mg bid in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. |
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| LNP023 50 mg bid/200 mg bid | Experimental | Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LNP023 | Drug | approximately 2 year of Treatment with LNP023 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Summary of Lactate Dehydrogenase (LDH) Responders | A responder was defined as a patient with at least 60% reduction in LDH compared to Baseline or LDH below the upper limit of normal at any time up to and including Week 12 for that patient. | Week 2, week 4, week 8 and week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in LDH Levels | LDH was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of Paroxysmal nocturnal hemoglobinuria (PNH)-associated hemolysis. Active hemolysis is defined by an LDH value ≥ 1.5x upper limit of normal (ULN) Baseline LDH was calculated as the average of the last three screening values prior to randomization. Serum was used to calculate the LDH values |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Kota Kinabalu | Sabah | 88586 | Malaysia | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35561315 | Result | Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022 Aug 9;6(15):4450-4460. doi: 10.1182/bloodadvances.2022006960. |
| Label | URL |
|---|---|
| Patient Lay Trial Summary | View source |
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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.
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Participants underwent a screening period of up to 8 weeks
Participants took part in 5 investigative sites in 4 countries
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| ID | Title | Description |
|---|---|---|
| FG000 | LNP023 25 mg Bid/100 mg Bid | Four weeks of treatment with iptacopan 25 mg bid in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. |
| FG001 | LNP023 50 mg Bid/200 mg Bid |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 3, 2021 | Jan 30, 2023 |
Randomized, open label study
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| Baseline, week 2, week 4, week 8 and week 12 |
| Change From Baseline in Hemoglobin | Hemoglobin was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of PNH-associated hemolysis. Whole blood was used to calculate the hemoglobin values. | Baseline, Week 2, week 4, week 8 and week 12 |
| Change From Baseline in Free Hemoglobin | Free hemoglobin was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of PNH-associated hemolysis. Whole blood was used to calculate the hemoglobin values. | Baseline, Week 2, week 4, week 8 and week 12 |
| Change From Baseline in Carboxyhemoglobin | Carboxyhemoglobin was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate the carboxyhemoglobin values. | Baseline, Week 2, week 4, week 8 and week 12 |
| Change From Baseline in Absolute Reticulocyte Count (ARC) | Reticulocyte count was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate the absolute reticulocyte count. | Baseline, week 2, week 4, week 8 and week 12 |
| Red Blood Cell Count: Change From Baseline in Erythrocytes | Erythrocytes were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate erythrocytes values. | Baseline, week 2, week 4, week 8 and week 12 |
| Change From Baseline in C3 Fragment Deposition on PNH RBC | C3 fragment deposition on paroxysmal nocturnal hemoglobinuria red blood cell (PNH RBC) was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Accumulation of C3 fragments on red blood cells make them prone to phagocytosis causing extravascular hemolysis. Whole blood was used to calculate C3 fragment deposition on PNH RBC values. | Baseline, week 2, week 4, week 8 and week 12 |
| Mean Haptoglobin Levels | Haptoglobin levels were used as a hemolysis marker to determine the effect of iptacopan on the reduction of PNH-associated hemolysis. Serum was used to calculate haptoglobin levels. | Baseline, week 2, week 4, week 8 and week 12 |
| Change From Baseline in Total Bilirubin | Bilirubin levels were used as a hemolysis marker to determine the effect of iptacopan on the reduction of PNH-associated hemolysis. Serum was used to calculate bilirubin levels. | Baseline, week 2, week 4, week 8 and week 12 |
| Mean Platelets Count | Platelet counts were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate platelets count. | Baseline, week 2, week 4, week 8 and week 12 |
| Mean Ferritin Levels | Ferritin levels were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Serum was used to calculate ferritin levels. | Baseline, Week 4, Week 8 and week 12 |
| Mean Clone Size | PNH clone size was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate clone size values. | Baseline, week 2, week 4, week 8 and week 12 |
| Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax) | Cmax is the maximum (peak) observed plasma drug concentration after single dose administration (mass x volume-1). PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data. | Day 29 and 57 |
| Pharmacokinetics Profile: Area Under the Curve Tau (AUCtau) | The AUCtau is the area under the plasma concentration-time curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1). AUCtau was estimated by imputing the 12-hour iptacopan plasma concentration as the PK profile's corresponding pre-dose (0-hour) value, that is, by assuming that at steady-state the iptacopan plasma concentration is the same as the beginning (pre-dose) and end (12 hours postdose) of the dosing interval. PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data. | Days 29 and 57 |
| Pharmacokinetics Profile: Minimum Plasma Concentration (Cmin) | Cmin is the lowest plasma concentration observed during a dosing interval at steady state [mass / volume]. PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data. | Days 29 and 57 |
| 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 parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data. | Days 29 and 57 |
| Mean Fibrinogen Levels | Fibrinogen level was used as a marker associated with risk of thrombosis. Plasma was used to calculate fibrinogen levels. | Baseline, week 2, week 4, week 8 and week 12 |
| Mean Prothrombin Time (PT) | Prothrombin time was used as a marker associated with risk of thrombosis. Plasma was used to calculate prothrombin time. | Baseline, week 2, week 4, week 8 and week 12 |
| Mean Activated Partial Thromboplastin Time (aPTT) | Activated partial thromboplastin time was used as a marker associated with risk of thrombosis. Plasma was used to calculate activated partial thromboplastin time. | Baseline, week 2, week 4, week 8 and week 12 |
| Mean D-dimer Levels | D-dimer levels were used as a marker associated with risk of thrombosis. Plasma was used to calculate D-dimer levels. | Baseline, week 2, week 4, week 8 and week 12 |
| Mean Thrombin Clotting Time | thrombin clotting time was used as a marker associated with risk of thrombosis. Plasma was used to calculate thrombin clotting time. | Baseline, Week 4, Week 8 and Week 12 |
| Singapore |
| 119228 |
| Singapore |
| Novartis Investigative Site | Seoul | 03080 | South Korea |
| Novartis Investigative Site | Seoul | 06351 | South Korea |
| Novartis Investigative Site | Taipei | 10002 | Taiwan |
Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3.
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | LNP023 25 mg Bid/100 mg Bid | Four weeks of treatment with iptacopan 25 mg bid in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. |
| BG001 | LNP023 50 mg Bid/200 mg Bid | Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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 | Summary of Lactate Dehydrogenase (LDH) Responders | A responder was defined as a patient with at least 60% reduction in LDH compared to Baseline or LDH below the upper limit of normal at any time up to and including Week 12 for that patient. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of LDH. The Pharmacodynamic (PD) analysis set is defined as patients with available PD data, who received any study drug and with no protocol deviations with relevant impact on PD data. The number analyzed per row represents the participants with a valid LDH value for that particular visit. | Posted | Count of Participants | Participants | Week 2, week 4, week 8 and week 12 |
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| Secondary | Percent Change From Baseline in LDH Levels | LDH was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of Paroxysmal nocturnal hemoglobinuria (PNH)-associated hemolysis. Active hemolysis is defined by an LDH value ≥ 1.5x upper limit of normal (ULN) Baseline LDH was calculated as the average of the last three screening values prior to randomization. Serum was used to calculate the LDH values | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of LDH. The number analyzed per row represents the participants with a valid LDH value at both baseline and that particular visit. | Posted | Mean | Standard Deviation | Percent change in LDH levels | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Change From Baseline in Hemoglobin | Hemoglobin was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of PNH-associated hemolysis. Whole blood was used to calculate the hemoglobin values. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of hemoglobin. The number analyzed per row represents the participants with a valid hemoglobin value both baseline and that particular visit. | Posted | Mean | Standard Deviation | g/L | Baseline, Week 2, week 4, week 8 and week 12 |
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| Secondary | Change From Baseline in Free Hemoglobin | Free hemoglobin was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of PNH-associated hemolysis. Whole blood was used to calculate the hemoglobin values. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of free hemoglobin. The number analyzed per row represents the participants with a valid free hemoglobin value both at baseline and that particular visit. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Week 2, week 4, week 8 and week 12 |
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| Secondary | Change From Baseline in Carboxyhemoglobin | Carboxyhemoglobin was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate the carboxyhemoglobin values. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of carboxyhemoglobin. The number analyzed per row represents the participants with a valid carboxyhemoglobin value both at baseline and that particular visit | Posted | Mean | Standard Deviation | Percentage of carboxyhemoglobin | Baseline, Week 2, week 4, week 8 and week 12 |
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| Secondary | Change From Baseline in Absolute Reticulocyte Count (ARC) | Reticulocyte count was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate the absolute reticulocyte count. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of reticulocyte count. 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, week 2, week 4, week 8 and week 12 |
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| Secondary | Red Blood Cell Count: Change From Baseline in Erythrocytes | Erythrocytes were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate erythrocytes values. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of erythrocytes. The number analyzed per row represents the participants with a valid erythrocytes value both at baseline and that particular visit. | Posted | Mean | Standard Deviation | 10^12 cells/L | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Change From Baseline in C3 Fragment Deposition on PNH RBC | C3 fragment deposition on paroxysmal nocturnal hemoglobinuria red blood cell (PNH RBC) was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Accumulation of C3 fragments on red blood cells make them prone to phagocytosis causing extravascular hemolysis. Whole blood was used to calculate C3 fragment deposition on PNH RBC values. | 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 | % C3 fragment deposition on PNH RBC | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Mean Haptoglobin Levels | Haptoglobin levels were used as a hemolysis marker to determine the effect of iptacopan on the reduction of PNH-associated hemolysis. Serum was used to calculate haptoglobin levels. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of haptoglobin. The number analyzed per row represents the participants with a valid haptoglobin value for that particular visit. | Posted | Mean | Standard Deviation | g/L | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Change From Baseline in Total Bilirubin | Bilirubin levels were used as a hemolysis marker to determine the effect of iptacopan on the reduction of PNH-associated hemolysis. Serum was used to calculate bilirubin levels. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of bilirubin. 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, week 2, week 4, week 8 and week 12 |
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| Secondary | Mean Platelets Count | Platelet counts were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate platelets count. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of platelets count. The number analyzed per row represents the participants with a valid platelets count value for that particular visit. | Posted | Mean | Standard Deviation | 10^9 cells/L | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Mean Ferritin Levels | Ferritin levels were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Serum was used to calculate ferritin levels. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of ferritin. The number analyzed per row represents the participants with a valid ferritin value for that particular visit. | Posted | Mean | Standard Deviation | ug/L | Baseline, Week 4, Week 8 and week 12 |
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| Secondary | Mean Clone Size | PNH clone size was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Whole blood was used to calculate clone size values. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of clone size. 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 Red Blood Cells | Baseline, week 2, week 4, week 8 and week 12 |
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| 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 parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data. | The overall number of participants analyzed represents the participants in the PK analysis set who had at least one valid measurement of Cmax. 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 29 and 57 |
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| Secondary | Pharmacokinetics Profile: Area Under the Curve Tau (AUCtau) | The AUCtau is the area under the plasma concentration-time curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1). AUCtau was estimated by imputing the 12-hour iptacopan plasma concentration as the PK profile's corresponding pre-dose (0-hour) value, that is, by assuming that at steady-state the iptacopan plasma concentration is the same as the beginning (pre-dose) and end (12 hours postdose) of the dosing interval. PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data. | The overall number of participants analyzed represents the participants in the PK analysis set who had at least one valid measurement of AUCtau. The number analyzed per row represents the participants with a valid AUCtau value for that particular visit. | Posted | Mean | Standard Deviation | h*ng/mL | Days 29 and 57 |
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| Secondary | Pharmacokinetics Profile: Minimum Plasma Concentration (Cmin) | Cmin is the lowest plasma concentration observed during a dosing interval at steady state [mass / volume]. PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data. | The overall number of participants analyzed represents the participants in the PK analysis set who had at least one valid measurement of Cmin. The number analyzed per row represents the participants with a valid Cmin value for that particular visit. | Posted | Mean | Standard Deviation | ng/mL | Days 29 and 57 |
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| 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 parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data. | The overall number of participants analyzed represents the participants in the PK analysis set who had at least one valid measurement of Tmax. The number analyzed per row represents the participants with a valid Tmax value for that particular visit. | Posted | Median | Full Range | hours | Days 29 and 57 |
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| Secondary | Mean Fibrinogen Levels | Fibrinogen level was used as a marker associated with risk of thrombosis. Plasma was used to calculate fibrinogen levels. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of fibrinogen. The number analyzed per row represents the participants with a valid fibrinogen value for that particular visit. | Posted | Mean | Standard Deviation | g/L | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Mean Prothrombin Time (PT) | Prothrombin time was used as a marker associated with risk of thrombosis. Plasma was used to calculate prothrombin time. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of prothrombin time. The number analyzed per row represents the participants with a valid prothrombin time value for that particular visit. | Posted | Mean | Standard Deviation | seconds | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Mean Activated Partial Thromboplastin Time (aPTT) | Activated partial thromboplastin time was used as a marker associated with risk of thrombosis. Plasma was used to calculate activated partial thromboplastin time. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of aPTT. The number analyzed per row represents the participants with a valid aPTT value for that particular visit. | Posted | Mean | Standard Deviation | seconds | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Mean D-dimer Levels | D-dimer levels were used as a marker associated with risk of thrombosis. Plasma was used to calculate D-dimer levels. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of D-dimer. The number analyzed per row represents the participants with a valid D-dimer value for that particular visit. | Posted | Mean | Standard Deviation | mg fibrinogen-equivalent unit (FEU)/L | Baseline, week 2, week 4, week 8 and week 12 |
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| Secondary | Mean Thrombin Clotting Time | thrombin clotting time was used as a marker associated with risk of thrombosis. Plasma was used to calculate thrombin clotting time. | The overall number of participants analyzed represents the participants in the PD analysis set who had at least one valid measurement of thrombin clotting time. The number analyzed per row represents the participants with a valid thrombin clotting time value for that particular visit. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 4, Week 8 and Week 12 |
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Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment, up to a maximum duration of 115 weeks.
AEs are reported by period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LNP023 25mg Bid - Period 1 | Four weeks of treatment with iptacopan 25 mg bid in Period 1 | 0 | 7 | 0 | 7 | 2 | 7 |
| EG001 | LNP023 50mg Bid - Period 1 | Four weeks of treatment with iptacopan 50 mg bid in Period 1 | 0 | 6 | 0 | 6 | 4 | 6 |
| EG002 | LNP023 100mg Bid - Period 2 | Eight weeks of treatment with iptacopan 100 mg bid in Period 2 | 0 | 7 | 0 | 7 | 3 | 7 |
| EG003 | LNP023 200mg Bid - Period 2 | Eight weeks of treatment with iptacopan 200 mg bid in Period 2 | 0 | 5 | 0 | 5 | 1 | 5 |
| EG004 | LNP023 100mg Bid - Period 3 | Two years of Extension Treatment with iptacopan 100 mg bid in Period 3 | 0 | 7 | 0 | 7 | 4 | 7 |
| EG005 | LNP023 200mg Bid - Period 3 | Two years of Extension Treatment with iptacopan 200 mg bid in Period 3 | 0 | 5 | 0 | 5 | 4 | 5 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Breakthrough haemolysis | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
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| Eosinophilia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
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| Haemolysis | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA (24.1) | Systematic Assessment |
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| Autoimmune thyroiditis | Endocrine disorders | MedDRA (24.1) | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | MedDRA (24.1) | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Enterocolitis | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Pain | General disorders | MedDRA (24.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (24.1) | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Antinuclear antibody increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Blood luteinising hormone increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Blood urine present | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Haematocrit increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Haemoglobin increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Reverse tri-iodothyronine increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Thyroxine free increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Impaired fasting glucose | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Chromaturia | 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 |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue 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 | Apr 14, 2022 | Jan 30, 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 |
Not provided
Not provided
Not provided
| Male |
|
| Responders at week 8 |
|
| Responders at week 12 |
|
| Participants |
|
|
|
|
|
|
|
| Counts |
|---|
| Participants |
|
|
|
|
|
|
|
| OG003 |
| LNP023 200 mg Bid |
Treatment with iptacopan 200 mg bid in Period 2 and Period 3. |
|
|
Treatment with iptacopan 100 mg bid in Period 2 and Period 3.
| OG003 | LNP023 200 mg Bid | Treatment with iptacopan 200 mg bid in Period 2 and Period 3 |
|
|
|
|
Treatment with iptacopan 200 mg bid in Period 2 and Period 3
|
|
|
|
|
|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|