Paroxysmal Nocturnal HemoglobinuriaPhase 2NCT03896152
Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria
A Phase 2 study testing LNP023 in people with Paroxysmal Nocturnal Hemoglobinuria, run by Novartis Pharmaceuticals at 5 sites in 4 countries.
Trial summary
This was a Phase II randomized, open-label, multicenter, efficacy, safety, pharmacokinetic and pharmacodynamic study assessing four iptacopan doses in adult Paroxysmal nocturnal hemoglobinuria (PNH) patients with active hemolysis who were not on eculizumab or any other complement inhibitor less than 3 months prior to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- LNP023
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 5 Apr 2019to 9 Feb 2022
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- Male and female patients at least 18 years old at baseline.
- Diagnosis of active PNH based on documented clone size of ≥10% by RBCs and/or granulocytes, measured by GPI-deficiency on flow cytometry (screening or medical history data acceptable).
- LDH values > 1.5 x upper limit of the normal range (ULN) for at least 3 measurements over a maximum of 8 weeks prior to Day 1 (Screening, baseline or medical history data acceptable).
- Hemoglobin level < 10.5 g/dL at Baseline.
- For Period 3 of the study, patients who as per judgment of Investigator benefit from LNP023 treatment based on reduced hemolytic parameters as compared to Screening and Baseline.
- Vaccinations against N. meningitidis, S. pneumoniae and H. influenzae is required at least 4 weeks prior to first dosing with LNP023 (existing vaccinations should provide effective titers at time of LNP023 treatment start). If LNP023 treatment has to start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment must be initiated.
- Able to communicate well with the investigator, to understand and comply with the requirements of the study. -
Who cannot join
- Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment, or within 5 elimination half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.
- Patients treated with eculizumab or any other complement inhibitor less than 3 months prior to study Day 1
- Known or suspected hereditary or acquired complement deficiency.
- History of currently active primary or secondary immunodeficiency.
- History of splenectomy.
- History of bone marrow/ hematopoietic stem cell or solid organ transplants (e.g. heart, lung, kidney, liver).
Show all 18Show fewer
- Evidence of malignant disease, or malignancies diagnosed within the previous 5 years.
- Patients with laboratory evidence of bone marrow failure (reticulocytes < 60x10E9/L, or platelets < 50x10E9/L or neutrophils < 1x10E9/L) verified both at screening and baseline.
- History of recurrent meningitis, history of meningococcal infections despite vaccination, as verified at both screening and baseline.
- Presence or suspicion (based on judgment of the investigator) of active infection within 2 weeks prior to first dose of LNP023, or history of severe recurrent bacterial infections.
- A positive HIV, Hepatitis B (HBV) or Hepatitis C (HCV) test result at screening.
- Patients on immunosuppressive agents such, as but not limited to, cyclosporine, tacrolimus, mycophenolate or mycophenolic acid, cyclophosphamide, methotrexate or IV immunoglobulins, less than 8 weeks prior to first treatment with LNP023, unless on a stable regimen for at least 3 months prior to first LNP023 dose.
- Systemic corticosteroids unless on a stable dose for at least 4 weeks before randomization.
- Severe concurrent co-morbidities not amenable to active treatment; e.g., patients with severe kidney disease (CKD stage 4, dialysis), advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), or unstable thrombotic event, as judged by the investigator, both at screening and baseline (unless baseline was skipped).
- Any medical condition deemed likely to interfere with the patient's participation in the study, or likely to cause serious adverse events during the study.
- History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
- Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
South Korea2 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 06351
About this study
Official title: A Multi-center, Randomized, Open-label, Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria and Active Hemolysis
This was a Phase II randomized, open-label, multicenter, efficacy, safety, pharmacokinetic and pharmacodynamic study assessing four iptacopan doses in adult Paroxysmal nocturnal hemoglobinuria (PNH) patients with active hemolysis who were not on eculizumab or any other complement inhibitor less than 3 months prior to first iptacopan dose. Active hemolysis was defined by a lactate dehydrogenase (LDH) value ≥ 1.5 × ULN.
Read the detailed description
LNP023 is a novel oral small molecular weight compound, that inhibits alternative complement pathway (AP). Blockade of the AP with oral LNP023 has the potential to prevent both intra - and extravascular hemolysis.
The total study duration from Screening until end of study (EOS) was approximately 28 months. This three-period study included:
- Screening phase: of up to 8 weeks
- Period 1: a 4-week treatment period of iptacopan at the first dose in the assigned sequence
- Period 2: an 8-week treatment period at the second dose in the assigned sequence
- Period 3: an approximate 2-year treatment extension period for patients who responded to iptacopan treatment
- Taper down period of 2 weeks was applicable only for patients discontinuing iptacopan treatment (Week 13 for non-responders or Week 109 for responders who did not enter the rollover extension program (REP) (Study CLNP023C12001B / NCT04747613)). During this taper down period, patients were to receive 25 mg qd (once a day) of iptacopan for 7 days, followed by 10 mg qd for 7 additional days.
- An EOS visit that took place 1 week after the last iptacopan administration for patients not joining the REP. For patients joining the REP, the last treatment visit was the EOS visit.
- A safety follow-up call 30 days after the last administration of iptacopan was performed for patients not joining the REP.
Patients were randomized to Sequence 1 or Sequence 2 in a 1:1 ratio. Sequence 1: Four weeks of treatment with iptacopan 25 mg bid (Twice daily) in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. If during Period 1, LDH was not reduced by ≥ 40% from the mean of pretreatment values by Week 2 (Day 15 study visit), the iptacopan dose was to be up-titrated to 100 mg bid (starting from Study Day 17). If LDH was not reduced by ≥ 40% from the mean of pretreatment values at Week 4 (Day 29), the iptacopan dose was to be up-titrated to 200 mg bid in Period 2 and Period 3 (starting from Study Day 30). In the approximate 2-year treatment extension (Period 3), patients maintained the same treatment regimen as used in Period 2.
Sequence 2: Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3. If during Period 1, LDH was not reduced by ≥ 40% from the mean of pretreatment values by Week 2 (Day 15 study visit), the iptacopan dose was to be up-titrated to 200 mg bid (starting from Study Day 17). In the approximate 2-year treatment extension (Extension Period 3), patients remained on 200 mg bid. No further up-titration was possible
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- LNP023
- Keywords
- Complement, alternative pathway, paroxysmal nocturnal hemoglobinuria, hemolysis, LNP023, PNH, LDH, hemoglobin, Iptacopan
- Medical subject headings
- Hemoglobinuria, Paroxysmal, Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LNP023Drug
Also called iptacopan
approximately 2 year of Treatment with LNP023
| Study group | Role | What they receive |
|---|---|---|
| LNP023 25 mg bid/100 mg bid | Experimental | Four weeks of treatment with iptacopan 25 mg bid in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. Receives: Drug: LNP023 |
| LNP023 50 mg bid/200 mg bid | Experimental | Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3. Receives: Drug: LNP023 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summary of Lactate Dehydrogenase (LDH) Responders
A responder was defined as a patient with at least 60% reduction in LDH compared to Baseline or LDH below the upper limit of normal at any time up to and including Week 12 for that patient.
Measured: Week 2, week 4, week 8 and week 12
Secondary outcomes (21)
Percent Change From Baseline in LDH Levels
LDH was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of Paroxysmal nocturnal hemoglobinuria (PNH)-associated hemolysis.
Active hemolysis is defined by an LDH value ≥ 1.5x upper limit of normal (ULN) Baseline LDH was calculated as the average of the last three screening values prior to randomization.
Serum was used to calculate the LDH values
Measured: Baseline, week 2, week 4, week 8 and week 12
Change From Baseline in Hemoglobin
Hemoglobin was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of PNH-associated hemolysis. Whole blood was used to calculate the hemoglobin values.
Measured: Baseline, Week 2, week 4, week 8 and week 12
Change From Baseline in Free Hemoglobin
Free hemoglobin was used as a hemolysis marker to determine the dose-response effect of iptacopan on the reduction of PNH-associated hemolysis.
Whole blood was used to calculate the hemoglobin values.
Measured: Baseline, Week 2, week 4, week 8 and week 12
Change From Baseline in Carboxyhemoglobin
Carboxyhemoglobin was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan.
Whole blood was used to calculate the carboxyhemoglobin values.
Measured: Baseline, Week 2, week 4, week 8 and week 12
Change From Baseline in Absolute Reticulocyte Count (ARC)
Reticulocyte count was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan.
Whole blood was used to calculate the absolute reticulocyte count.
Measured: Baseline, week 2, week 4, week 8 and week 12
Red Blood Cell Count: Change From Baseline in Erythrocytes
Erythrocytes were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan.
Whole blood was used to calculate erythrocytes values.
Measured: Baseline, week 2, week 4, week 8 and week 12
Change From Baseline in C3 Fragment Deposition on PNH RBC
C3 fragment deposition on paroxysmal nocturnal hemoglobinuria red blood cell (PNH RBC) was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan. Accumulation of C3 fragments on red blood cells make them prone to phagocytosis causing extravascular hemolysis.
Whole blood was used to calculate C3 fragment deposition on PNH RBC values.
Measured: Baseline, week 2, week 4, week 8 and week 12
Mean Haptoglobin Levels
Haptoglobin levels were used as a hemolysis marker to determine the effect of iptacopan on the reduction of PNH-associated hemolysis.
Serum was used to calculate haptoglobin levels.
Measured: Baseline, week 2, week 4, week 8 and week 12
Change From Baseline in Total Bilirubin
Bilirubin levels were used as a hemolysis marker to determine the effect of iptacopan on the reduction of PNH-associated hemolysis.
Serum was used to calculate bilirubin levels.
Measured: Baseline, week 2, week 4, week 8 and week 12
Mean Platelets Count
Platelet counts were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan.
Whole blood was used to calculate platelets count.
Measured: Baseline, week 2, week 4, week 8 and week 12
Mean Ferritin Levels
Ferritin levels were used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan.
Serum was used to calculate ferritin levels.
Measured: Baseline, Week 4, Week 8 and week 12
Mean Clone Size
PNH clone size was used as a marker of intravascular and extravascular hemolysis to assess the effect of iptacopan.
Whole blood was used to calculate clone size values.
Measured: Baseline, week 2, week 4, week 8 and week 12
Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax)
Cmax is the maximum (peak) observed plasma drug concentration after single dose administration (mass x volume-1).
PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data.
Measured: Day 29 and 57
Pharmacokinetics Profile: Area Under the Curve Tau (AUCtau)
The AUCtau is the area under the plasma concentration-time curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
AUCtau was estimated by imputing the 12-hour iptacopan plasma concentration as the PK profile's corresponding pre-dose (0-hour) value, that is, by assuming that at steady-state the iptacopan plasma concentration is the same as the beginning (pre-dose) and end (12 hours postdose) of the dosing interval.
PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data.
Measured: Days 29 and 57
Pharmacokinetics Profile: Minimum Plasma Concentration (Cmin)
Cmin is the lowest plasma concentration observed during a dosing interval at steady state [mass / volume].
PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data.
Measured: Days 29 and 57
Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax)
Tmax is the time to reach maximum (peak) plasma drug concentration after single dose administration (time).
PK parameters were determined, using non-compartmental method(s) with Phoenix WinNonlin (Version 8.3), from the plasma concentration-time data.
Measured: Days 29 and 57
Mean Fibrinogen Levels
Fibrinogen level was used as a marker associated with risk of thrombosis. Plasma was used to calculate fibrinogen levels.
Measured: Baseline, week 2, week 4, week 8 and week 12
Mean Prothrombin Time (PT)
Prothrombin time was used as a marker associated with risk of thrombosis. Plasma was used to calculate prothrombin time.
Measured: Baseline, week 2, week 4, week 8 and week 12
Mean Activated Partial Thromboplastin Time (aPTT)
Activated partial thromboplastin time was used as a marker associated with risk of thrombosis.
Plasma was used to calculate activated partial thromboplastin time.
Measured: Baseline, week 2, week 4, week 8 and week 12
Mean D-dimer Levels
D-dimer levels were used as a marker associated with risk of thrombosis. Plasma was used to calculate D-dimer levels.
Measured: Baseline, week 2, week 4, week 8 and week 12
Mean Thrombin Clotting Time
thrombin clotting time was used as a marker associated with risk of thrombosis. Plasma was used to calculate thrombin clotting time.
Measured: Baseline, Week 4, Week 8 and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2019
- Study start5 Apr 2019
- Primary completion7 Apr 2020
- Study completion9 Feb 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, open label study
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03896152
- Sponsor's protocol ID
- CLNP023X2204
- Status last verified
- Jun 2024
- First submitted
- 28 Mar 2019
- Last updated
- 18 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- 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.
Publications
Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022 Aug 9;6(15):4450-4460. doi: 10.1182/bloodadvances.2022006960.
PubMed 35561315
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Open-label, Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria and Active Hemolysis
- ClinicalTrials.gov ID
- NCT03896152
- Acronym / sponsor ID
- CLNP023X2204
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Keywords
- Complement, alternative pathway, paroxysmal nocturnal hemoglobinuria, hemolysis, LNP023, PNH, LDH, hemoglobin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 5 Apr 2019 (actual)
- Primary completion
- 7 Apr 2020 (actual)
- Study completion
- 9 Feb 2022 (actual)
- First posted
- 29 Mar 2019 (actual)
- Results
- Posted 18 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase II randomized, open-label, multicenter, efficacy, safety, pharmacokinetic and pharmacodynamic study assessing four iptacopan doses in adult Paroxysmal nocturnal hemoglobinuria (PNH) patients with active hemolysis who were not on eculizumab or any other complement inhibitor less than 3 months prior to first iptacopan dose. Active hemolysis was defined by a lactate dehydrogenase (LDH) value ≥ 1.5 × ULN.
Detailed description
LNP023 is a novel oral small molecular weight compound, that inhibits alternative complement pathway (AP). Blockade of the AP with oral LNP023 has the potential to prevent both intra - and extravascular hemolysis.
The total study duration from Screening until end of study (EOS) was approximately 28 months. This three-period study included:
- Screening phase: of up to 8 weeks
- Period 1: a 4-week treatment period of iptacopan at the first dose in the assigned sequence
- Period 2: an 8-week treatment period at the second dose in the assigned sequence
- Period 3: an approximate 2-year treatment extension period for patients who responded to iptacopan treatment
- Taper down period of 2 weeks was applicable only for patients discontinuing iptacopan treatment (Week 13 for non-responders or Week 109 for responders who did not enter the rollover extension program (REP) (Study CLNP023C12001B / NCT04747613)). During this taper down period, patients were to receive 25 mg qd (once a day) of iptacopan for 7 days, followed by 10 mg qd for 7 additional days.
- An EOS visit that took place 1 week after the last iptacopan administration for patients not joining the REP. For patients joining the REP, the last treatment visit was the EOS visit.
- A safety follow-up call 30 days after the last administration of iptacopan was performed for patients not joining the REP.
Patients were randomized to Sequence 1 or Sequence 2 in a 1:1 ratio. Sequence 1: Four weeks of treatment with iptacopan 25 mg bid (Twice daily) in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. If during Period 1, LDH was not reduced by ≥ 40% from the mean of pretreatment values by Week 2 (Day 15 study visit), the iptacopan dose was to be up-titrated to 100 mg bid (starting from Study Day 17). If LDH was not reduced by ≥ 40% from the mean of pretreatment values at Week 4 (Day 29), the iptacopan dose was to be up-titrated to 200 mg bid in Period 2 and Period 3 (starting from Study Day 30). In the approximate 2-year treatment extension (Period 3), patients maintained the same treatment regimen as used in Period 2.
Sequence 2: Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3. If during Period 1, LDH was not reduced by ≥ 40% from the mean of pretreatment values by Week 2 (Day 15 study visit), the iptacopan dose was to be up-titrated to 200 mg bid (starting from Study Day 17). In the approximate 2-year treatment extension (Extension Period 3), patients remained on 200 mg bid. No further up-titration was possible
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, open label study
| Arm | Type | Receives |
|---|---|---|
| LNP023 25 mg bid/100 mg bid | Experimental | Drug: LNP023Four weeks of treatment with iptacopan 25 mg bid in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. |
| LNP023 50 mg bid/200 mg bid | Experimental | Drug: LNP023Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent must be obtained before any assessment is performed.
- Male and female patients at least 18 years old at baseline.
- Diagnosis of active PNH based on documented clone size of ≥10% by RBCs and/or granulocytes, measured by GPI-deficiency on flow cytometry (screening or medical history data acceptable).
- LDH values > 1.5 x upper limit of the normal range (ULN) for at least 3 measurements over a maximum of 8 weeks prior to Day 1 (Screening, baseline or medical history data acceptable).
- Hemoglobin level < 10.5 g/dL at Baseline.
Key exclusion criteria (18 listed)
- Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment, or within 5 elimination half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.
- Patients treated with eculizumab or any other complement inhibitor less than 3 months prior to study Day 1
- Known or suspected hereditary or acquired complement deficiency.
- History of currently active primary or secondary immunodeficiency.
- History of splenectomy.
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 |
|---|---|---|
| LNP023Also: iptacopanapproximately 2 year of Treatment with LNP023 | Drug | LNP023 25 mg bid/100 mg bid, LNP023 50 mg bid/200 mg bid |
Primary outcome
Summary of Lactate Dehydrogenase (LDH) Responders
Time frame: Week 2, week 4, week 8 and week 12
A responder was defined as a patient with at least 60% reduction in LDH compared to Baseline or LDH below the upper limit of normal at any time up to and including Week 12 for that patient.
21 secondary outcomes
Percent Change From Baseline in LDH Levels
Time frame: Baseline, week 2, week 4, week 8 and week 12
Change From Baseline in Hemoglobin
Time frame: Baseline, Week 2, week 4, week 8 and week 12
Change From Baseline in Free Hemoglobin
Time frame: Baseline, Week 2, week 4, week 8 and week 12
Change From Baseline in Carboxyhemoglobin
Time frame: Baseline, Week 2, week 4, week 8 and week 12
Change From Baseline in Absolute Reticulocyte Count (ARC)
Time frame: Baseline, week 2, week 4, week 8 and week 12
Red Blood Cell Count: Change From Baseline in Erythrocytes
Time frame: Baseline, week 2, week 4, week 8 and week 12
Change From Baseline in C3 Fragment Deposition on PNH RBC
Time frame: Baseline, week 2, week 4, week 8 and week 12
Mean Haptoglobin Levels
Time frame: Baseline, week 2, week 4, week 8 and week 12
Change From Baseline in Total Bilirubin
Time frame: Baseline, week 2, week 4, week 8 and week 12
Mean Platelets Count
Time frame: Baseline, week 2, week 4, week 8 and week 12
Mean Ferritin Levels
Time frame: Baseline, Week 4, Week 8 and week 12
Mean Clone Size
Time frame: Baseline, week 2, week 4, week 8 and week 12
Pharmacokinetics Profile: Maximum Plasma Concentration (Cmax)
Time frame: Day 29 and 57
Pharmacokinetics Profile: Area Under the Curve Tau (AUCtau)
Time frame: Days 29 and 57
Pharmacokinetics Profile: Minimum Plasma Concentration (Cmin)
Time frame: Days 29 and 57
Pharmacokinetics Profile: Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: Days 29 and 57
Mean Fibrinogen Levels
Time frame: Baseline, week 2, week 4, week 8 and week 12
Mean Prothrombin Time (PT)
Time frame: Baseline, week 2, week 4, week 8 and week 12
Mean Activated Partial Thromboplastin Time (aPTT)
Time frame: Baseline, week 2, week 4, week 8 and week 12
Mean D-dimer Levels
Time frame: Baseline, week 2, week 4, week 8 and week 12
Mean Thrombin Clotting Time
Time frame: Baseline, Week 4, Week 8 and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 35561315Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022 Aug 9;6(15):4450-4460. doi: 10.1182/bloodadvances.2022006960.
- Patient Lay Trial SummaryLink 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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LNP023 in people with Paroxysmal Nocturnal Hemoglobinuria, run by Novartis Pharmaceuticals at 5 sites in 4 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 18 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 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in South Korea, Malaysia, Singapore, Taiwan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 18 Dec 2023). 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?
Summary of Lactate Dehydrogenase (LDH) Responders (time frame: Week 2, week 4, week 8 and week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03896152, which also lists 1 linked publication.
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 18 Jun 2024.