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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-502148-10-00 | Other Identifier | EU CT |
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The purpose of the study was to find out if iptacopan is effective and safe in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who switched from their current standard of care treatment (eculizumab or ravulizumab) to study treatment, iptacopan/LNP023.
This was a multicenter, single-arm, open label trial, with iptacopan treatment for 24 weeks in adult PNH patients.
This study was comprised of two periods:
After completion of the treatment period, participants who continued to benefit from the iptacopan treatment based on the study doctor's evaluation were able to join the Roll-over extension study (CLNP023C12001B).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LNP023 200mg b.i.d. | Experimental | Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Iptacopan | Drug | Treatment with iptacopan at a dose of 200 mg b.i.d. will start on the first day (Day 1) and continue for 24 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority | Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. The estimation of change from baseline in Hb levels was handled by the hypothetical strategy where participants were assumed as if they did not receive RBC transfusions while on treatment (RBC transfusions were expected to be rare). Assuming that participants had stable Hb levels at study entry, the mean change from baseline in Hb level between Day 126 and Day 168 was expected to be unchanged should participants have continued on anti-C5 treatment. Non-inferiority of iptacopan was therefore tested by the null hypothesis (H0) against the alternate hypothesis (H1) comparing the mean change from baseline in Hb level in iptacopan between Day 126 and Day 168 (μ) to -1 g/dL: H0: μ <= -1, H1: μ > -1. | Baseline, Day 126 to Day 168 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Superiority | Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. | Baseline, Day 126 to Day 168 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City Of Hope National Med Center | Duarte | California | 91010 | United States | ||
| USC Norris Cancer Center |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | 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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The study consisted of a screening period up to 8 weeks.
A total of 23 centers; 9 in United States, 4 in Germany, 3 in France, 2 in the United Kingdom, 2 in Italy and one each in Spain, Turkey and Republic of Korea enrolled participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | LNP023 200mg b.i.d. | Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally |
| 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 | Dec 12, 2023 | Oct 8, 2025 |
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A multicenter, single arm, open-label trial to evaluate efficacy and safety of oral, twice daily iptacopan in adult PNH patients who have Hb≥10 g/dL in response to anti-C5 antibody and switch to iptacopan
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| Proportion of Hematological Responders to Iptacopan Treatment | Response defined as Hb ≥12 g/dL assessed between visits Day 126 and Day 168 in the absence of RBC transfusions, on three out of four measurements taken at the visits occurring in last six weeks | Day 126 to Day 168 |
| Proportion of Participants Who Remain Free From Transfusions | Number of participants with absence of administration of packed RBC transfusions between Day 1 and Day 168 | Day 1 to Day 168 |
| Change From Baseline in Absolute Reticulocytes Count (ARC) Levels | Change from baseline in ARC levels as mean of visits between Day 126 and Day 168 | Baseline, Day 126 to Day 168 |
| Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Percentage change from baseline in LDH levels as mean of visits between Day 126 and Day 168 | Baseline, Day 126 to Day 168 |
| Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire | Difference in scores of the Treatment Satisfaction Questionnaire for Medication(TSQM-9) between baseline and Day 84 and Day 168 assessed after switching from SoC (anti-C5) to iptacopan. TSQM-9 is a patient reported outcomes measure that was designed to assess patients' satisfaction with medication across three domains of effectiveness, convenience and global satisfaction. The TSQM-9 contains 3 questions in each domain. Domain scores range from 0 - 100 with higher scores representing better outcomes for the domain. | Baseline, Day 84 and Day 168 |
| Change From Baseline in Fatigue Score Using FACIT-F Questionnaire | Change from baseline in patient-reported scores for the functional assessment of chronic illness therapy - Fatigue (FACIT-F) collected at Day 84 and Day 168. The FACIT-F is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best. | Baseline, Day 84 and Day 168 |
| Percentage of Patients Who Had Breakthrough Hemolysis (BTH) Event | Wilson method is used to calculate the confidence interval for the proportion of patients who had events. The breakthrough is defined clinical if either there is a decrease in hemoglobin levels equal to or more than 2 g/dL (compared to the latest assessment) or if patients present signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia or any other significant clinical PNH-related signs & symptoms, in presence of laboratory evidence of intravascular hemolysis. | Up to 168 Days |
| Percentage of Patients Who Had Major Adverse Vascular Events (MAVEs) | A MAVE is defined as: acute peripheral vascular occlusion, amputation (non-traumatic; nondiabetic), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, dermal thrombosis, gangrene (non-traumatic; nondiabetic), hepatic/portal vein thrombosis (Budd-Chiari syndrome), mesenteric/visceral arterial thrombosis or infarction, mesenteric/visceral vein thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial thrombosis, renal vein thrombosis, thrombophlebitis / deep vein thrombosis, transient ischemic attack, unstable angina or other. | Up to 168 Days |
| Los Angeles |
| California |
| 90033 |
| United States |
| Lakes Research | Miami Lakes | Florida | 33014 | United States |
| Mass Gen Hosp Cancer Center | Boston | Massachusetts | 02114 | United States |
| University Of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Prisma Health Upstate | Greenville | South Carolina | 29615 | United States |
| Huntsman Cancer Institute Univ of Utah | Salt Lake City | Utah | 84112 0550 | United States |
| Novartis Investigative Site | Nantes | 44093 | France |
| Novartis Investigative Site | Nice | 06202 | France |
| Novartis Investigative Site | Paris | 75475 | France |
| Novartis Investigative Site | Dresden | Saxony | 01307 | Germany |
| Novartis Investigative Site | Aachen | 52074 | Germany |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Ulm | 89081 | Germany |
| Novartis Investigative Site | Florence | FI | 50134 | Italy |
| Novartis Investigative Site | Bassano del Grappa | VI | 36061 | Italy |
| Novartis Investigative Site | Seoul | Seoul | 06351 | South Korea |
| Novartis Investigative Site | Barcelona | 08036 | Spain |
| Novartis Investigative Site | Istanbul | Fatih | 34093 | Turkey (Türkiye) |
| Novartis Investigative Site | Leeds | West Yorkshire | LS9 7TF | United Kingdom |
| Novartis Investigative Site | London | SE5 9RS | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | LNP023 200mg b.i.d. | Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally |
| 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, Categorical | Count of Participants | Participants |
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| 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 | Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority | Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. The estimation of change from baseline in Hb levels was handled by the hypothetical strategy where participants were assumed as if they did not receive RBC transfusions while on treatment (RBC transfusions were expected to be rare). Assuming that participants had stable Hb levels at study entry, the mean change from baseline in Hb level between Day 126 and Day 168 was expected to be unchanged should participants have continued on anti-C5 treatment. Non-inferiority of iptacopan was therefore tested by the null hypothesis (H0) against the alternate hypothesis (H1) comparing the mean change from baseline in Hb level in iptacopan between Day 126 and Day 168 (μ) to -1 g/dL: H0: μ <= -1, H1: μ > -1. | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at baseline and Day 126 and Day 168. | Posted | Mean | 95% Confidence Interval | g/dL | Baseline, Day 126 to Day 168 |
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| Secondary | Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Superiority | Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at baseline and Day 126 and Day 168. | Posted | Mean | 95% Confidence Interval | g/dL | Baseline, Day 126 to Day 168 |
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| Secondary | Proportion of Hematological Responders to Iptacopan Treatment | Response defined as Hb ≥12 g/dL assessed between visits Day 126 and Day 168 in the absence of RBC transfusions, on three out of four measurements taken at the visits occurring in last six weeks | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at Day 126 and Day 168. | Posted | Number | 95% Confidence Interval | Proportion of participants | Day 126 to Day 168 |
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| Secondary | Proportion of Participants Who Remain Free From Transfusions | Number of participants with absence of administration of packed RBC transfusions between Day 1 and Day 168 | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | Proportion of participants | Day 1 to Day 168 |
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| Secondary | Change From Baseline in Absolute Reticulocytes Count (ARC) Levels | Change from baseline in ARC levels as mean of visits between Day 126 and Day 168 | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at Day 126 and Day 168. | Posted | Mean | 95% Confidence Interval | 10^9 cells/L | Baseline, Day 126 to Day 168 |
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| Secondary | Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Percentage change from baseline in LDH levels as mean of visits between Day 126 and Day 168 | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at Day 126 and Day 168. | Posted | Mean | 95% Confidence Interval | Percent change from baseline in LDH | Baseline, Day 126 to Day 168 |
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| Secondary | Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire | Difference in scores of the Treatment Satisfaction Questionnaire for Medication(TSQM-9) between baseline and Day 84 and Day 168 assessed after switching from SoC (anti-C5) to iptacopan. TSQM-9 is a patient reported outcomes measure that was designed to assess patients' satisfaction with medication across three domains of effectiveness, convenience and global satisfaction. The TSQM-9 contains 3 questions in each domain. Domain scores range from 0 - 100 with higher scores representing better outcomes for the domain. | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at baseline, Day 84 and Day 168. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline, Day 84 and Day 168 |
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| Secondary | Change From Baseline in Fatigue Score Using FACIT-F Questionnaire | Change from baseline in patient-reported scores for the functional assessment of chronic illness therapy - Fatigue (FACIT-F) collected at Day 84 and Day 168. The FACIT-F is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best. | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. The number of participants analyzed corresponds to the number of subjects who had values at Day 84 and Day 168. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline, Day 84 and Day 168 |
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| Secondary | Percentage of Patients Who Had Breakthrough Hemolysis (BTH) Event | Wilson method is used to calculate the confidence interval for the proportion of patients who had events. The breakthrough is defined clinical if either there is a decrease in hemoglobin levels equal to or more than 2 g/dL (compared to the latest assessment) or if patients present signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia or any other significant clinical PNH-related signs & symptoms, in presence of laboratory evidence of intravascular hemolysis. | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | Percentage of patients with BTH events | Up to 168 Days |
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| Secondary | Percentage of Patients Who Had Major Adverse Vascular Events (MAVEs) | A MAVE is defined as: acute peripheral vascular occlusion, amputation (non-traumatic; nondiabetic), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, dermal thrombosis, gangrene (non-traumatic; nondiabetic), hepatic/portal vein thrombosis (Budd-Chiari syndrome), mesenteric/visceral arterial thrombosis or infarction, mesenteric/visceral vein thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial thrombosis, renal vein thrombosis, thrombophlebitis / deep vein thrombosis, transient ischemic attack, unstable angina or other. | Full Analysis Set (FAS) comprised all participants with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | Percentage of patients with MAVEs | Up to 168 Days |
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Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment for non-serious AEs and 30 days post treatment for serious AEs if patient did not roll over to REP study, up to a maximum duration of 198 days
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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 200mg b.i.d. | Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally | 0 | 52 | 2 | 52 | 25 | 52 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders and administration site conditions | MedDRA (27.1) | Systematic Assessment |
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| Pneumonia bacterial | Infections and infestations | MedDRA (27.1) | Systematic Assessment |
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| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA (27.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (27.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (27.1) | Systematic Assessment |
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| Fatigue | General disorders and administration site conditions | MedDRA (27.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (27.1) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (27.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (27.1) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (27.1) | Systematic Assessment |
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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 | Oct 30, 2024 | Oct 8, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006457 | Hemoglobinuria, Paroxysmal |
| ID | Term |
|---|---|
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009190 | Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |
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| ID | Term |
|---|---|
| C000730766 | iptacopan |
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| Not Reported |
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| Unknown |
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