Trial · NCT04820530
Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy
NCT04820530, Phase 3, Completed, Novartis Pharmaceuticals; results first posted 2023-11-15
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy. Trials, record NCT04820530. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04820530
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy
- NCT number
- NCT04820530
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 40 participants, actual
- Lead sponsor
- Novartis Pharmaceuticals
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Interventions
- Iptacopan (LNP023)
- First posted
- 2021-03-29
- Last updated
- 2024-10-09
- Other registries' IDs
- eudract:2020-003172-41
- Results first posted
- 2023-11-15
Source ClinicalTrials.gov
Registered outcomes17
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| 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 | Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 | 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. |
| Secondary | Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 | 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. |
| Secondary | Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions | Between Day 14 and Day 168 | 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 |
| Secondary | Change From Baseline in Hemoglobin Levels in the Core Treatment Period | Baseline, Day 126 to 168 | 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. |
| Secondary | Percent Change From Baseline in LDH | Baseline, Day 126 to 168 | 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. |
| Secondary | Adjusted Annualized Clinical BTH Rate in the Core Treatment Period | Between Day 1 and Day 168 | 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. |
| Secondary | Change From Baseline in Absolute Reticulocyte Count | Baseline and mean of visits between Day 126 and 168 | 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. |
| Secondary | Change From Baseline in FACIT-Fatigue Score | Baseline and mean of visits between Day 126 and Day 168 | 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. |
| Secondary | Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period | Between Day 1 and Day 168 | 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. |
| Other | Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions | Baseline, Day 336 | 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. |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 registered outcomesOutcomes17
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| 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 | Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Percentage of responders | NUMBER |
| SECONDARY | Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Percentage of responders | NUMBER |
| SECONDARY | Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions | Between Day 14 and Day 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Percentage of participants | NUMBER |
| SECONDARY | Change From Baseline in Hemoglobin Levels in the Core Treatment Period | Baseline, Day 126 to 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | g/dL | MEAN |
| SECONDARY | Percent Change From Baseline in LDH | Baseline, Day 126 to 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | Percent change from baseline in LDH | MEAN |
| SECONDARY | Adjusted Annualized Clinical BTH Rate in the Core Treatment Period | Between Day 1 and Day 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | BTH events/year | NUMBER |
| SECONDARY | Change From Baseline in Absolute Reticulocyte Count | Baseline and mean of visits between Day 126 and 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | x10^9 cells/L | MEAN |
| SECONDARY | Change From Baseline in FACIT-Fatigue Score | Baseline and mean of visits between Day 126 and Day 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | score on a scale | MEAN |
| SECONDARY | Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period | Between Day 1 and Day 168 | Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. | MAVE events/year | NUMBER |
| OTHER_PRE_SPECIFIED | Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions | Baseline, 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. | Percentage of participants | NUMBER |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 outcomesResults by group18
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| 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 | LNP023 | 92.2 | 95% Confidence Interval 82.5 to 100.0 | Percentage of responders | |
| Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | LNP023 | 62.8 | 95% Confidence Interval 47.5 to 77.5 | Percentage of responders | |
| Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions | LNP023 | 97.6 | 95% Confidence Interval 92.5 to 100.0 | Percentage of participants | |
| Change From Baseline in Hemoglobin Levels in the Core Treatment Period | LNP023 | 4.28 | 95% Confidence Interval 3.87 to 4.70 | g/dL | |
| Percent Change From Baseline in LDH | LNP023 | -83.55 | 95% Confidence Interval -84.90 to -82.08 | Percent change from baseline in LDH | |
| Adjusted Annualized Clinical BTH Rate in the Core Treatment Period | LNP023 | 0.00 | 95% Confidence Interval 0.00 to 0.17 | BTH events/year | |
| Change From Baseline in Absolute Reticulocyte Count | LNP023 | -82.48 | 95% Confidence Interval -89.33 to -75.62 | x10^9 cells/L | |
| Change From Baseline in FACIT-Fatigue Score | LNP023 | 10.75 | 95% Confidence Interval 8.66 to 12.84 | score on a scale | |
| Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period | LNP023 | 0.00 | 95% Confidence Interval 0.00 to 0.17 | MAVE events/year | |
| Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions | LNP023 | ≥2 g/dL increase in Hb from baseline irrespective of RBC transfusions | 97.4 | Percentage of participants |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Core Treatment Period | STARTED | LNP023 | 40 | |
| Core Treatment Period | COMPLETED | LNP023 | 40 | |
| Core Treatment Period | NOT COMPLETED | LNP023 | 0 | |
| Extension Treatment Period | STARTED | LNP023 | 40 | |
| Extension Treatment Period | COMPLETED | LNP023 | 40 | |
| Extension Treatment Period | NOT COMPLETED | LNP023 | 0 |
Source ClinicalTrials.gov
Adverse events17
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Abdominal pain | Gastrointestinal disorders | LNP023 200mg b.i.d. | 3 | 40 | |
| other | Constipation | Gastrointestinal disorders | LNP023 200mg b.i.d. | 3 | 40 | |
| other | Diarrhoea | Gastrointestinal disorders | LNP023 200mg b.i.d. | 6 | 40 | |
| other | Vomiting | Gastrointestinal disorders | LNP023 200mg b.i.d. | 3 | 40 | |
| other | Pyrexia | General disorders | LNP023 200mg b.i.d. | 3 | 40 | |
| other | COVID-19 | Infections and infestations | LNP023 200mg b.i.d. | 7 | 40 | |
| other | Upper respiratory tract infection | Infections and infestations | LNP023 200mg b.i.d. | 7 | 40 | |
| other | Iron deficiency | Metabolism and nutrition disorders | LNP023 200mg b.i.d. | 3 | 40 | |
| other | Headache | Nervous system disorders | LNP023 200mg b.i.d. | 12 | 40 | |
| serious | Breakthrough haemolysis | Blood and lymphatic system disorders | LNP023 200mg b.i.d. | 1 | 40 |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 adverse eventsAdverse event totals3
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | LNP023 200mg b.i.d. | 0 | 40 |
| Total, other adverse events | LNP023 200mg b.i.d. | 24 | 40 |
| Total, serious adverse events | LNP023 200mg b.i.d. | 8 | 40 |
Source ClinicalTrials.gov
Papers3
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT04820530
GET https://conductscience.org/api/trials/v1/NCT04820530/registered