Paroxysmal Nocturnal HemoglobinuriaPhase 3APPULSENCT05630001
Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.
A Phase 3 study testing Iptacopan in people with Paroxysmal Nocturnal Hemoglobinuria, run by Novartis Pharmaceuticals at 23 sites in 8 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- Iptacopan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 23 sitesin 8 countries
- Study dates
- 24 Apr 2023to 17 Oct 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent must be obtained prior to participation in the study.
- Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician.
- Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening
- Mean hemoglobin level ≥10 g/dL
- Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment.
- If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations.
- Ability to communicate well with the investigator, to understand and comply with the requirements of the study
- Other protocol -defined inclusion criteria may apply at the end.
Who cannot join
- Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment
- Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening
- History of stem cell transplantation or any solid organ transplantation
- Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration
- Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration
- Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening)
Show all 12Show fewer
- A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
- Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening.
- History of cancer of any part of the body within the past 5 years,
- Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial.
- Any medical condition deemed likely to interfere with the patient's participation in the study
- Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study
Trial locations and contacts
23 sites in 8 countries.
23 sites in 8 countries
United States9 sites
Mass Gen Hosp Cancer Center
Boston, Massachusetts, 02114
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
City Of Hope National Med Center
Duarte, California, 91010
Prisma Health Upstate
Greenville, South Carolina, 29615
USC Norris Cancer Center
Los Angeles, California, 90033
Lakes Research
Miami Lakes, Florida, 33014
University Of Minnesota
Minneapolis, Minnesota, 55455
Huntsman Cancer Institute Univ of Utah
Salt Lake City, Utah, 84112 0550
Montefiore Medical Center
The Bronx, New York, 10461
Germany4 sites
Novartis Investigative Site
Aachen, 52074
Novartis Investigative Site
Dresden, Saxony, 01307
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Ulm, 89081
France3 sites
Novartis Investigative Site
Nantes, 44093
Novartis Investigative Site
Nice, 06202
Novartis Investigative Site
Paris, 75475
Italy2 sites
Novartis Investigative Site
Bassano del Grappa, VI, 36061
Novartis Investigative Site
Florence, FI, 50134
United Kingdom2 sites
Novartis Investigative Site
Leeds, West Yorkshire, LS9 7TF
Novartis Investigative Site
London, SE5 9RS
Turkey (Türkiye)1 site
Novartis Investigative Site
Istanbul, Fatih, 34093
About this study
Official title: 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
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.
Read the detailed description
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:
- A Screening period lasting up to 8 weeks.
- A 24-week open-label, iptacopan Treatment period.
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).
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- Iptacopan
- Keywords
- Paroxysmal Nocturnal Hemoglobinuria, iptacopan, single arm open-label, Hb≥10 g/dL in response to anti-C5 antibody, switch to iptacopan, PNH, LNP023
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IptacopanDrug
Also called LNP023
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.
| Study group | Role | What they receive |
|---|---|---|
| LNP023 200mg b.i.d. | Experimental | Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally Receives: Drug: Iptacopan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Day 126 to Day 168
Secondary outcomes (9)
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.
Measured: Baseline, Day 126 to Day 168
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 168 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2022
- Study start24 Apr 2023
- Primary completion17 Oct 2024
- Study completion17 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05630001
- Sponsor's protocol ID
- CLNP023C12303
- Other IDs
- 2022-502148-10-00
- Acronym
- APPULSE
- Status last verified
- Dec 2025
- First submitted
- 18 Nov 2022
- Last updated
- 13 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05630001
- Acronym / sponsor ID
- APPULSE / CLNP023C12303
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Keywords
- Paroxysmal Nocturnal Hemoglobinuria, iptacopan, single arm open-label, Hb≥10 g/dL in response to anti-C5 antibody, switch to iptacopan, PNH, LNP023
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Apr 2023 (actual)
- Primary completion
- 17 Oct 2024 (actual)
- Study completion
- 17 Oct 2024 (actual)
- First posted
- 29 Nov 2022 (actual)
- Results
- Posted 15 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- A Screening period lasting up to 8 weeks.
- A 24-week open-label, iptacopan Treatment period.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| LNP023 200mg b.i.d. | Experimental | Drug: IptacopanIptacopan (LNP023) at a dose of 200 mg b.i.d. orally |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed informed consent must be obtained prior to participation in the study.
- Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician.
- Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening
- Mean hemoglobin level ≥10 g/dL
- Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment.
Key exclusion criteria (12 listed)
- Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment
- Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening
- History of stem cell transplantation or any solid organ transplantation
- Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration
- Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IptacopanAlso: LNP023Treatment with iptacopan at a dose of 200 mg b.i.d. will start on the first day (Day 1) and continue for 24 weeks. | Drug | LNP023 200mg b.i.d. |
Primary outcome
Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority
Time frame: Baseline, Day 126 to Day 168
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.
9 secondary outcomes
Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Superiority
Time frame: Baseline, Day 126 to Day 168
Proportion of Hematological Responders to Iptacopan Treatment
Time frame: Day 126 to Day 168
Proportion of Participants Who Remain Free From Transfusions
Time frame: Day 1 to Day 168
Change From Baseline in Absolute Reticulocytes Count (ARC) Levels
Time frame: Baseline, Day 126 to Day 168
Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Levels
Time frame: Baseline, Day 126 to Day 168
Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire
Time frame: Baseline, Day 84 and Day 168
Change From Baseline in Fatigue Score Using FACIT-F Questionnaire
Time frame: Baseline, Day 84 and Day 168
Percentage of Patients Who Had Breakthrough Hemolysis (BTH) Event
Time frame: Up to 168 Days
Percentage of Patients Who Had Major Adverse Vascular Events (MAVEs)
Time frame: Up to 168 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
23 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Iptacopan in people with Paroxysmal Nocturnal Hemoglobinuria, run by Novartis Pharmaceuticals at 23 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Germany, France, Italy, United Kingdom and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority (time frame: Baseline, Day 126 to Day 168). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2026.