Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003172-41 | 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
The purpose of this Phase 3 study was to determine whether iptacopan is efficacious and safe for the treatment of Paroxysmal nocturnal hemoglobinuria (PNH) patients who were naïve to complement inhibitor therapy.
This study was a multicenter, single-arm, open-label trial which was comprised of 8 weeks screening period, 24-week core treatment period and 24-week extension treatment period.
Eligible PNH patients with hemolysis (LDH > 1.5 ULN) and anemia (hemoglobin <10 g/dL), who were naive to complement inhibitor therapy, including anti-C5 antibody treatment, received iptacopan monotherapy at a dose 200 mg orally b.i.d.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LNP023 | Experimental | Participants receive LNP023 at a dose of 200 mg orally b.i.d |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Iptacopan (LNP023) | Drug | Taken orally b.i.d. Dosage supplied: 200mg Dosage form: Hard gelatin capsule Route of Administration: oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions | Sustained increase in hemoglobin levels (responder) is defined as an increase from baseline in hemoglobin levels of ≥ 2 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the primary analysis. | Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 |
| Measure | Description | Time Frame |
|---|---|---|
| Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | Sustained hemoglobin levels (responder) is defined as hemoglobin levels ≥ 12 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the analysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions | Patients with hematological response are those with an increase in Hb from baseline ≥ 2g/dL irrespective of red blood cell (RBC) transfusions and patients achieving Hb ≥ 12g/dL irrespective of RBC transfusions. | Baseline, Day 336 |
Inclusion Criteria:
Exclusion Criteria:
Not provided
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 | Beijing | 100730 | China | |||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40694294 | Derived | DeCastro C, Sheinberg P, Han B, Vallow S, Bermann G, Dhalke M, Kumar R, Dickie G, Galipeau N, Lamoureux R, Rupinski K, Lowe C, Nieves A, de Fontbrune FS, de Latour RP. Patient-Reported Meaningful Change in Symptoms and Impacts of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Three Phase III Clinical Trials of Iptacopan. Patient. 2025 Nov;18(6):699-712. doi: 10.1007/s40271-025-00755-5. Epub 2025 Jul 22. | |
| 40447351 |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | 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 provided written informed consent prior to the start of any study-related activities.
Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections was required prior to the start of treatment.
Participants took part in 12 investigative sites in 8 countries: France(1), United Kingdom(1), Italy(1), Korea, Republic of(1), Singapore(1), China(3), Malaysia(2), Germany(2)
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | LNP023 | Participants receive LNP023 at a dose of 200 mg b.i.d. orally |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Core Treatment Period |
|
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 | Mar 28, 2022 | Mar 18, 2024 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 |
| Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions | Marginal proportion (expressed as percentage) of participants who did not require transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. The 95% CI was obtained using the bootstrap method | Between Day 14 and Day 168 |
| Change From Baseline in Hemoglobin Levels in the Core Treatment Period | Change from baseline in hemoglobin levels as mean of visits between Day 126 and Day 168. In order to factor out the effect of transfusions in this analysis, if a patient had a transfusion during the core treatment period, the hemoglobin (Hb) values during 30 days following the transfusion were excluded and Hb data were imputed. Change from baseline was analyzed using a mixed model of repeated measures which included age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, and baseline hemoglobin as fixed effects and the interaction between visit and baseline hemoglobin levels. | Baseline, Day 126 to 168 |
| Percent Change From Baseline in LDH | Percent change from baseline in lactate dehydrogenase (LDH) levels as mean of visits between Day 126 and Day 168. Percentage change from baseline was analyzed using a mixed model for repeated measures (MMRM) which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline LDH as fixed effects and visit*baseline LDH as interaction. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the analysis. | Baseline, Day 126 to 168 |
| Adjusted Annualized Clinical BTH Rate in the Core Treatment Period | Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events is carried out using the Wilson method. 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 within 15 days) 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. | Between Day 1 and Day 168 |
| Change From Baseline in Absolute Reticulocyte Count | Change from baseline in absolute reticulocyte counts as mean of visits between Day 126 and Day 168. Change from baseline was analyzed using a MMRM which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline reticulocyte counts as fixed effects and visit*baseline reticulocyte counts as interaction. | Baseline and mean of visits between Day 126 and 168 |
| Change From Baseline in FACIT-Fatigue Score | Change from baseline in FACIT-Fatigue scores as mean of visits between Day 126 and Day 168. The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on 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. Change from baseline was analyzed using a Mixed Model of Repeated Measures (MMRM) which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline FACIT-Fatigue score as fixed effects and visit*baseline FACIT-Fatigue score as interaction. | Baseline and mean of visits between Day 126 and Day 168 |
| Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period | Adjusted annual rate is carried out using the Wilson method. 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. | Between Day 1 and Day 168 |
| Marginal Proportion (Expressed as Percentage) of Patients Not Receiving and Not Requiring RBC Transfusions |
Requiring Red Blood Cells (RBC) transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). |
| Between Day 14 and Day 336 |
| Change From Baseline in Hemoglobin Levels | Change from baseline in Hemoglobin at Visit Day 336 | Baseline, Day 336 |
| Change From Baseline in LDH at Visit Day 336 | Change from baseline in Lactate dehydrogenase (LDH) at Visit Day 336 | Baseline, Day 336 |
| Adjusted Annualized Clinical BTH Rate After the Start of LNP023 Treatment | Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events is carried out using the Wilson method. 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 within 15 days) 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. | Between Day 1 and Day 336 |
| Change From Baseline in Absolute Reticulocyte Count at Day 336 | Change from baseline in absolute reticulocyte count at visit Day 336. | Baseline, Day 336 |
| Change From Baseline in FACIT-Fatigue Score | The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on 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 336 |
| Adjusted Annualized Major Adverse Vascular Events Rate After the Start of LNP023 Treatment | Adjusted annual rate is carried out using the Wilson method. A Major Adverse Vascular Events (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 | Between Day 1 and Day 336 |
| Tianjin |
| 300020 |
| China |
| Novartis Investigative Site | Tianjin | 300052 | China |
| Novartis Investigative Site | Paris | 75475 | France |
| Novartis Investigative Site | Aachen | 52074 | Germany |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Avellino | AV | 83100 | Italy |
| Novartis Investigative Site | Kota Kinabalu | Sabah | 88586 | Malaysia |
| Novartis Investigative Site | Kuching | Sarawak | 93586 | Malaysia |
| Novartis Investigative Site | Singapore | 119228 | Singapore |
| Novartis Investigative Site | Seoul | 06351 | South Korea |
| Novartis Investigative Site | London | SE5 9RS | United Kingdom |
| Derived |
| Risitano AM, Kulasekararaj AG, Scheinberg P, Roth A, Han B, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Lee LWL, Yap ES, Frieri C, Marano L, de Fontbrune FS, Gandhi S, Trikha R, Alashkar F, Yang C, Liu H, Kelly RJ, Hochsmann B, Lawniczek T, Mahajan N, Solar-Yohay S, Kerloeguen C, Ferber P, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, de Latour RP. Oral iptacopan monotherapy in paroxysmal nocturnal haemoglobinuria: final 48-week results from the open-label, randomised, phase 3 APPLY-PNH trial in anti-C5-treated patients and the open-label, single-arm, phase 3 APPOINT-PNH trial in patients previously untreated with complement inhibitors. Lancet Haematol. 2025 Jun;12(6):e414-e430. doi: 10.1016/S2352-3026(25)00081-X. |
| 38477987 | Derived | Peffault de Latour R, Roth A, Kulasekararaj AG, Han B, Scheinberg P, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Wong Lee Lee L, Yap ES, Sicre de Fontbrune F, Marano L, Alashkar F, Gandhi S, Trikha R, Yang C, Liu H, Kelly RJ, Hochsmann B, Kerloeguen C, Banerjee P, Levitch R, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, Risitano AM. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2024 Mar 14;390(11):994-1008. doi: 10.1056/NEJMoa2308695. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Extension Treatment Period |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | LNP023 | Participants receive LNP023 at a dose of 200 mg b.i.d. orally |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions | Sustained increase in hemoglobin levels (responder) is defined as an increase from baseline in hemoglobin levels of ≥ 2 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the primary analysis. | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | Percentage of responders | Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 |
|
|
| |||||||||||||||||||||||||
| Secondary | Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | Sustained hemoglobin levels (responder) is defined as hemoglobin levels ≥ 12 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the analysis. | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | Percentage of responders | Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 |
|
| ||||||||||||||||||||||||||
| Secondary | Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions | Marginal proportion (expressed as percentage) of participants who did not require transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. The 95% CI was obtained using the bootstrap method | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | Percentage of participants | Between Day 14 and Day 168 |
|
| ||||||||||||||||||||||||||
| Secondary | Change From Baseline in Hemoglobin Levels in the Core Treatment Period | Change from baseline in hemoglobin levels as mean of visits between Day 126 and Day 168. In order to factor out the effect of transfusions in this analysis, if a patient had a transfusion during the core treatment period, the hemoglobin (Hb) values during 30 days following the transfusion were excluded and Hb data were imputed. Change from baseline was analyzed using a mixed model of repeated measures which included age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, and baseline hemoglobin as fixed effects and the interaction between visit and baseline hemoglobin levels. | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Mean | 95% Confidence Interval | g/dL | Baseline, Day 126 to 168 |
|
| ||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in LDH | Percent change from baseline in lactate dehydrogenase (LDH) levels as mean of visits between Day 126 and Day 168. Percentage change from baseline was analyzed using a mixed model for repeated measures (MMRM) which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline LDH as fixed effects and visit*baseline LDH as interaction. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the analysis. | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Mean | 95% Confidence Interval | Percent change from baseline in LDH | Baseline, Day 126 to 168 |
|
| ||||||||||||||||||||||||||
| Secondary | Adjusted Annualized Clinical BTH Rate in the Core Treatment Period | Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events is carried out using the Wilson method. 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 within 15 days) 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): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | BTH events/year | Between Day 1 and Day 168 |
|
| ||||||||||||||||||||||||||
| Secondary | Change From Baseline in Absolute Reticulocyte Count | Change from baseline in absolute reticulocyte counts as mean of visits between Day 126 and Day 168. Change from baseline was analyzed using a MMRM which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline reticulocyte counts as fixed effects and visit*baseline reticulocyte counts as interaction. | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Mean | 95% Confidence Interval | x10^9 cells/L | Baseline and mean of visits between Day 126 and 168 |
|
| ||||||||||||||||||||||||||
| Secondary | Change From Baseline in FACIT-Fatigue Score | Change from baseline in FACIT-Fatigue scores as mean of visits between Day 126 and Day 168. The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on 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. Change from baseline was analyzed using a Mixed Model of Repeated Measures (MMRM) which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline FACIT-Fatigue score as fixed effects and visit*baseline FACIT-Fatigue score as interaction. | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline and mean of visits between Day 126 and Day 168 |
|
| ||||||||||||||||||||||||||
| Secondary | Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period | Adjusted annual rate is carried out using the Wilson method. 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): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | MAVE events/year | Between Day 1 and Day 168 |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions | Patients with hematological response are those with an increase in Hb from baseline ≥ 2g/dL irrespective of red blood cell (RBC) transfusions and patients achieving Hb ≥ 12g/dL irrespective of RBC transfusions. | Full analysis set: All patients with confirmed eligibility to whom study treatment was assigned. Only participants with valid Hb measurements at Day 336 were analyzed. | Posted | Number | Percentage of participants | Baseline, Day 336 |
|
| |||||||||||||||||||||||||||
| Other Pre-specified | Marginal Proportion (Expressed as Percentage) of Patients Not Receiving and Not Requiring RBC Transfusions | Requiring Red Blood Cells (RBC) transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). | Full analysis set: All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | Percentage of participants | Between Day 14 and Day 336 |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline in Hemoglobin Levels | Change from baseline in Hemoglobin at Visit Day 336 | Full analysis set: All patients with confirmed eligibility to whom study treatment was assigned. Only participants with valid Hb measurements at Day 336 were analyzed. | Posted | Mean | Standard Deviation | g/dL | Baseline, Day 336 |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline in LDH at Visit Day 336 | Change from baseline in Lactate dehydrogenase (LDH) at Visit Day 336 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Mean | Standard Deviation | U/L | Baseline, Day 336 |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | Adjusted Annualized Clinical BTH Rate After the Start of LNP023 Treatment | Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events is carried out using the Wilson method. 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 within 15 days) 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): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | BTH events/year | Between Day 1 and Day 336 |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline in Absolute Reticulocyte Count at Day 336 | Change from baseline in absolute reticulocyte count at visit Day 336. | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. Only participants with valid absolute reticulocyte count measurements at baseline and Day 336 were analyzed. | Posted | Mean | Standard Deviation | x10^9 cells/L | Baseline, Day 336 |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline in FACIT-Fatigue Score | The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on 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): All patients with confirmed eligibility to whom study treatment was assigned. Only participants with valid FACIT-Fatigue scores at baseline and Day 336 were analyzed. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Day 336 |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | Adjusted Annualized Major Adverse Vascular Events Rate After the Start of LNP023 Treatment | Adjusted annual rate is carried out using the Wilson method. A Major Adverse Vascular Events (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): All patients with confirmed eligibility to whom study treatment was assigned. | Posted | Number | 95% Confidence Interval | MAVE events/year | Between Day 1 and Day 336 |
|
|
Adverse events of LNP023 group were reported from first dose of study treatment until the end of study treatment plus up to 30 days, up to a maximum duration of 48 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 | LNP023 200mg b.i.d. | LNP023 200mg b.i.d. | 0 | 40 | 8 | 40 | 24 | 40 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Breakthrough haemolysis | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA (26.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (26.0) | 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_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 17, 2022 | Mar 18, 2024 | SAP_003.pdf |
| ID | Term |
|---|---|
| D006457 | Hemoglobinuria, Paroxysmal |
| D000740 | Anemia |
| ID | Term |
|---|---|
| D000743 | Anemia, Hemolytic |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009190 | Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000730766 | iptacopan |
Not provided
Not provided
Not provided
| Asian |
|
| Participants |
|
|
|
|
|
|
|
|
|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| Title | Denominators | Categories |
|---|
|
|
|
|
|