Trial · NCT04558918
Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment
NCT04558918, Phase 3, Completed, Novartis Pharmaceuticals; results first posted 2023-11-28
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment. Trials, record NCT04558918. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04558918
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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 LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment
- NCT number
- NCT04558918
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 97 participants, actual
- Lead sponsor
- Novartis Pharmaceuticals
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Interventions
- LNP023, Eculizumab, Ravulizumab
- First posted
- 2020-09-22
- Last updated
- 2024-10-09
- Other registries' IDs
- eudract:2019-004665-40
- Results first posted
- 2023-11-28
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 Percentages) 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 ≥ 2 g/dL on three out of four measurements taken at the visits occurring in last six weeks (between Day 126 and 168) of the randomized 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 ≤ 9 g/dL with signs /and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤ 7 g/dL, 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 for each treatment group. These values include adjustment for baseline covariates and missing data has also been taken into account. |
| Primary | Marginal Proportion (Expressed as Percentages) of Participants 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 taken at the visits occurring in last six weeks (between Day 126 and 168) of the randomized 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 ≤ 9 g/dL with signs /and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤ 7 g/dL, 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 for each treatment group. These values include adjustment for baseline covariates and missing data has also been taken into account. |
| Primary | Percentage of Patients Meeting Hematological Response Criterion After the Start of LNP023 Treatment | Up to 48 weeks | Patients with hematological response are those with ≥ 2g/dL increase in hemoglobin from baseline regardless of transfusions and patients with Hb ≥ 12g/dL regardless of transfusions. Patients in the LNP023-LNP023 group received iptacopan from Day 1 to Day 336 (48 weeks) while patients in the anti-C5 antibody-LNP023 group received iptacopan from Day 169 to Day 336 (treatment extension period - 24 weeks). |
| Primary | Number of Patients Not Requiring RBC Transfusions After the Start of LNP023 Treatment | Up to 48 weeks | Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level ≤ 9 g/dL with signs /and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤ 7 g/dL, regardless of presence of clinical signs and/or symptoms). Patients randomized to anti-C5 treatment switched to LNP023 (iptacopan) on Day 169 and were treated until Day 336 (treatment extension period). |
| Primary | Change From Baseline in Hemoglobin at Visit Day 336 | Baseline, Day 336 | Patients randomized to anti-C5 treatment switched to LNP023 (iptacopan) on Day 169 and were treated until Day 336 (treatment extension period). |
| Primary | Change From Baseline in FACIT-Fatigue Questionnaire at Day 336 | Baseline, Day 336 | 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. Patients randomized to anti-C5 treatment switched to LNP023 (iptacopan) on Day 169 and were treated until Day 336 (treatment extension period). |
| Primary | Adjusted Annualized Clinical BTH Rate After the Start of LNP023 Treatment | Up to 336 Days | This endpoint is considering clinical BTH events after the start of LNP023 treatment. Therefore, results are presented in a single arm on LNP023 since it includes all patients in the Combined Full analysis set. Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events are from negative binomial model. A patient with multiple occurrences of an event under one treatment is counted only once for that treatment.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. |
| Primary | Adjusted Annualized Major Adverse Vascular Events Rate After the Start of LNP023 Treatment | Up to 336 Days | This endpoint is considering clinical BTH events after the start of LNP023 treatment. Therefore, results are presented in a single arm on LNP023 since it includes all patients in the Combined Full analysis set. Adjusted annualized Major Adverse Vascular Events (MAVEs incl. thrombosis) rate. 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. A patient with multiple occurrences of an event under one treatment is counted only once for that treatment. |
| Secondary | Marginal Proportion (Expressed as Percentages) of Participants Who Remain Free From Transfusions | Between Day 14 and Day 168 | Marginal proportion (expressed as percentages) of participants who did not require transfusions between Day 14 and Day 168. Requiring red blood cell transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level ≤ 9 g/dL with signs /and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤ 7 g/dL, 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 for each treatment group. These values include adjustment for baseline covariates and missing data has also been taken into account. |
| Secondary | Change From Baseline in Hemoglobin Between Day 126 and 168 | Baseline and mean of visits between Day 126 and 168 | Change from baseline in hemoglobin levels as mean of visits between Day 126 and Day 168. For this analysis, in order to factor out the effect of transfusions, if a patient had a transfusion during the randomized treatment period, then the hemoglobin values 30 days following the transfusion were excluded and hemoglobin data were imputed. |
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 Percentages) 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): patients to whom study treatment had been assigned by randomization. | Percentage of responders | NUMBER |
| PRIMARY | Marginal Proportion (Expressed as Percentages) of Participants 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): patients to whom study treatment had been assigned by randomization. | Percentage of responders | NUMBER |
| PRIMARY | Percentage of Patients Meeting Hematological Response Criterion After the Start of LNP023 Treatment | Up to 48 weeks | Combined Full Analysis Set: includes all patients randomized to LNP023 200 mg b.i.d and all patients randomized to anti-C5 treatment and who switched to LNP023 in the treatment extension period. | Percentage of participants | NUMBER |
| PRIMARY | Number of Patients Not Requiring RBC Transfusions After the Start of LNP023 Treatment | Up to 48 weeks | Combined Full Analysis Set: includes all patients randomized to LNP023 200 mg b.i.d and all patients randomized to anti-C5 treatment and who switched to LNP023 in the treatment extension period. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Change From Baseline in Hemoglobin at Visit Day 336 | Baseline, Day 336 | Full Analysis Set (FAS): patients to whom study treatment had been assigned by randomization. Only participants with valid HB measurements at baseline and Day 336 were analyzed. | g/dL | MEAN |
| PRIMARY | Change From Baseline in FACIT-Fatigue Questionnaire at Day 336 | Baseline, Day 336 | Full Analysis Set (FAS): patients to whom study treatment had been assigned by randomization. Only participants with valid FACIT-Fatigue scores at baseline and Day 336 were analyzed. | score on a scale | MEAN |
| SECONDARY | Marginal Proportion (Expressed as Percentages) of Participants Who Remain Free From Transfusions | Between Day 14 and Day 168 | Full Analysis Set (FAS): patients to whom study treatment had been assigned by randomization. | Percentage of participants | NUMBER |
| SECONDARY | Change From Baseline in Hemoglobin Between Day 126 and 168 | Baseline and mean of visits between Day 126 and 168 | Full Analysis Set (FAS): patients to whom study treatment had been assigned by randomization. | g/dL | MEAN |
| SECONDARY | Change From Baseline in FACIT-Fatigue Questionnaire in the Randomized Treatment Period | Baseline, mean of visits between Day 126 and Day 168 | Full Analysis Set (FAS): patients to whom study treatment had been assigned by randomization. Only participants with valid FACIT-Fatigue scores at baseline and between day 126 and day 168 were analyzed. | score on a scale | MEAN |
| SECONDARY | Change From Baseline in Absolute Reticulocyte Count in the Randomized Treatment Period | Baseline and mean of visits between Day 126 and 168 | Full Analysis Set (FAS): patients to whom study treatment had been assigned by randomization. | x10^9 cells/L | MEAN |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 outcomesResults by group36
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 Percentages) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions | LNP023 200mg b.i.d. | 82.3 | 95% Confidence Interval 73.4 to 90.2 | Percentage of responders | |
| Marginal Proportion (Expressed as Percentages) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions | Anti-C5 Antibody | 2.0 | 95% Confidence Interval 1.1 to 4.0 | Percentage of responders | |
| Marginal Proportion (Expressed as Percentages) of Participants With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | LNP023 200mg b.i.d. | 68.8 | 95% Confidence Interval 58.4 to 78.9 | Percentage of responders | |
| Marginal Proportion (Expressed as Percentages) of Participants With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | Anti-C5 Antibody | 1.8 | 95% Confidence Interval 0.9 to 4.0 | Percentage of responders | |
| Percentage of Patients Meeting Hematological Response Criterion After the Start of LNP023 Treatment | LNP023 200mg b.i.d. | ≥2 g/dL increase in Hb from baseline irrespective of RBC transfusions | 86.4 | Percentage of participants | |
| Percentage of Patients Meeting Hematological Response Criterion After the Start of LNP023 Treatment | Anti-C5 Antibody | ≥2 g/dL increase in Hb from baseline irrespective of RBC transfusions | 72.4 | Percentage of participants | |
| Percentage of Patients Meeting Hematological Response Criterion After the Start of LNP023 Treatment | LNP023 200mg b.i.d. | Hb ≥12 g/dL irrespective of RBC transfusions | 67.8 | Percentage of participants | |
| Percentage of Patients Meeting Hematological Response Criterion After the Start of LNP023 Treatment | Anti-C5 Antibody | Hb ≥12 g/dL irrespective of RBC transfusions | 58.6 | Percentage of participants | |
| Number of Patients Not Requiring RBC Transfusions After the Start of LNP023 Treatment | LNP023 200mg b.i.d. | Since Day 1 of LNP023 treatment | 51 | Participants | |
| Number of Patients Not Requiring RBC Transfusions After the Start of LNP023 Treatment | Anti-C5 Antibody | Since Day 1 of LNP023 treatment | 31 | Participants |
1 to 10 of 36Source ClinicalTrials.gov
See all 36 results by groupParticipant flow16
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Randomized Treatment Period | STARTED | LNP023 200mg b.i.d. | 62 | |
| Randomized Treatment Period | STARTED | Anti-C5 Antibody | 35 | |
| Randomized Treatment Period | COMPLETED | LNP023 200mg b.i.d. | 62 | |
| Randomized Treatment Period | COMPLETED | Anti-C5 Antibody | 35 | |
| Randomized Treatment Period | NOT COMPLETED | LNP023 200mg b.i.d. | 0 | |
| Randomized Treatment Period | NOT COMPLETED | Anti-C5 Antibody | 0 | |
| Extension Treatment Period | STARTED | LNP023 200mg b.i.d. | 61 | |
| Extension Treatment Period | STARTED | Anti-C5 Antibody | 34 | |
| Extension Treatment Period | Full Analysis Set | LNP023 200mg b.i.d. | 62 | |
| Extension Treatment Period | Full Analysis Set | Anti-C5 Antibody | 35 |
1 to 10 of 16Source ClinicalTrials.gov
See all 16 participant flowAdverse events172
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 | Breakthrough haemolysis | Blood and lymphatic system disorders | LNP023 200mg b.i.d. (Randomized Treatment Period) | 2 | 62 | |
| other | Breakthrough haemolysis | Blood and lymphatic system disorders | Anti-C5 Antibody (Randomized Treatment Period) | 6 | 35 | |
| other | Breakthrough haemolysis | Blood and lymphatic system disorders | LNP023 200mg b.i.d. (Randomized Treatment Period + Extension Treatment Period) | 6 | 62 | |
| other | Breakthrough haemolysis | Blood and lymphatic system disorders | Any LNP023 200mg b.i.d. (Randomized Treatment Period + Extension Treatment Period) | 7 | 96 | |
| other | Thrombocytopenia | Blood and lymphatic system disorders | LNP023 200mg b.i.d. (Randomized Treatment Period) | 3 | 62 | |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Anti-C5 Antibody (Randomized Treatment Period) | 0 | 35 | |
| other | Thrombocytopenia | Blood and lymphatic system disorders | LNP023 200mg b.i.d. (Randomized Treatment Period + Extension Treatment Period) | 3 | 62 | |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Any LNP023 200mg b.i.d. (Randomized Treatment Period + Extension Treatment Period) | 5 | 96 | |
| other | Abdominal pain | Gastrointestinal disorders | LNP023 200mg b.i.d. (Randomized Treatment Period) | 4 | 62 | |
| other | Abdominal pain | Gastrointestinal disorders | Anti-C5 Antibody (Randomized Treatment Period) | 1 | 35 |
1 to 10 of 172Source ClinicalTrials.gov
See all 172 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | LNP023 200mg b.i.d. (Randomized Treatment Period) | 0 | 62 |
| Total, all-cause mortality | Anti-C5 Antibody (Randomized Treatment Period) | 0 | 35 |
| Total, all-cause mortality | LNP023 200mg b.i.d. (Randomized Treatment Period + Extension Treatment Period) | 0 | 62 |
| Total, all-cause mortality | Any LNP023 200mg b.i.d. (Randomized Treatment Period + Extension Treatment Period) | 0 | 96 |
| Total, other adverse events | LNP023 200mg b.i.d. (Randomized Treatment Period) | 34 | 62 |
| Total, other adverse events | Anti-C5 Antibody (Randomized Treatment Period) | 21 | 35 |
| Total, other adverse events | LNP023 200mg b.i.d. (Randomized Treatment Period + Extension Treatment Period) | 43 | 62 |
| Total, other adverse events | Any LNP023 200mg b.i.d. (Randomized Treatment Period + Extension Treatment Period) | 62 | 96 |
| Total, serious adverse events | LNP023 200mg b.i.d. (Randomized Treatment Period) | 6 | 62 |
| Total, serious adverse events | Anti-C5 Antibody (Randomized Treatment Period) | 5 | 35 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers3
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.
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