A Phase 2 interventional study of LNP023 in Paroxysmal Nocturnal Hemoglobinuria, sponsored by Novartis Pharmaceuticals. Completed at 5 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-18.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2, Interventional, and Treatment
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.
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:
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
191 studies on the registry are indexed under Hemoglobinuria, Paroxysmal; 49 are open to participants now.
This study's enrollment of 13 is below the median of 33 across 150 interventional studies indexed under Hemoglobinuria, Paroxysmal.
Browse Hemoglobinuria, Paroxysmal studies →Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: LNP023
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.
Drug: LNP023
approximately 2 year of Treatment with LNP023
Also known as: iptacopan
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.
Time frame: Week 2, week 4, week 8 and week 12
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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 4, Week 8 and Week 12
Participants took part in 5 investigative sites in 4 countries
| Milestone | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Started | 7 | 6 |
| Completed | 4 | 4 |
| Not completed | 3 | 2 |
| Withdrew: Patient/guardian decision | 1 | 1 |
| Withdrew: Adverse event | 0 | 1 |
| Withdrew: Physician decision | 1 | 0 |
| Withdrew: Technical problems | 1 | 0 |
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.
| Participants | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Responders at week 2 | 6 | 5 |
| Responders at week 4 | 7 | 5 |
| Responders at week 8 | 7 | 5 |
| Responders at week 12 | 7 | 5 |
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
| Percent change in LDH levels | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Week 2 | -76.52 ± 18.478 | -84.98 ± 8.186 |
| Week 4 | -79.75 ± 16.025 | -89.72 ± 5.430 |
| Week 8 | -81.73 ± 22.832 | -88.30 ± 8.744 |
| Week 12 | -86.17 ± 8.896 | -85.92 ± 9.013 |
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.
| g/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Week 2 | 6.88 ± 5.812 | 31.83 ± 10.362 |
| Week 4 | 9.61 ± 11.857 | 36.58 ± 17.875 |
| Week 8 | 15.02 ± 9.154 | 38.08 ± 25.956 |
| Week 12 | 23.36 ± 14.378 | 37.11 ± 26.171 |
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.
| mg/dL | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Week 2 | -39.84 ± 26.521 | -13.53 ± 5.093 |
| Week 4 | -31.88 ± 35.314 | -29.26 ± 24.218 |
| Week 8 | -31.85 ± 27.517 | -16.31 ± 48.877 |
| Week 12 | -39.58 ± 31.612 | -14.75 ± 6.293 |
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.
| Percentage of carboxyhemoglobin | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Week 2 | -0.01 ± 0.516 | -0.72 ± 0.697 |
| Week 4 | -0.36 ± 0.472 | -0.98 ± 0.582 |
| Week 8 | -0.50 ± 0.664 | -1.12 ± 0.916 |
| Week 12 | -0.95 ± 0.316 | -0.78 ± 1.704 |
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.
| 10^9 cells/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Week 2 | -83.00 ± 78.750 | -94.23 ± 112.649 |
| Week 4 | -118.44 ± 76.736 | -132.63 ± 91.109 |
| Week 8 | -113.71 ± 72.300 | -119.43 ± 117.048 |
| Week 12 | -93.00 ± 93.425 | -84.92 ± 123.408 |
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.
| 10^12 cells/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Week 2 | 0.49 ± 0.194 | 1.02 ± 0.407 |
| Week 4 | 0.74 ± 0.401 | 1.26 ± 0.619 |
| Week 8 | 1.16 ± 0.396 | 1.38 ± 0.796 |
| Week 12 | 1.38 ± 0.531 | 1.38 ± 0.770 |
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.
| % C3 fragment deposition on PNH RBC | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Week 2 | -1.31 ± 0.932 | -1.88 ± 1.457 |
| Week 4 | -1.43 ± 1.217 | -2.74 ± 2.584 |
| Week 8 | -1.85 ± 1.293 | -2.90 ± 2.654 |
| Week 12 | -1.65 ± 1.221 | -2.75 ± 3.002 |
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.
| g/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 0.05 ± 0.000 | 0.05 ± 0.000 |
| Week 2 | 0.27 ± 0.251 | 0.41 ± 0.499 |
| Week 4 | 0.24 ± 0.255 | 0.49 ± 0.490 |
| Week 8 | 0.38 ± 0.456 | 0.41 ± 0.374 |
| Week 12 | 0.25 ± 0.356 | 0.18 ± 0.225 |
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.
| umol/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Week 2 | -19.81 ± 7.855 | -23.93 ± 16.735 |
| Week 4 | -19.95 ± 10.620 | -25.93 ± 15.992 |
| Week 8 | -20.24 ± 12.612 | -25.53 ± 16.471 |
| Week 12 | -21.61 ± 5.998 | -23.17 ± 18.195 |
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.
| 10^9 cells/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 190.45 ± 59.938 | 156.42 ± 52.321 |
| Week 2 | 223.71 ± 76.707 | 158.20 ± 62.683 |
| Week 4 | 203.17 ± 68.520 | 138.20 ± 57.085 |
| Week 8 | 184.43 ± 50.856 | 141.20 ± 46.569 |
| Week 12 | 189.33 ± 54.617 | 140.75 ± 59.618 |
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.
| ug/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 176.97 ± 404.254 | 258.90 ± 418.114 |
| Week 4 | 174.21 ± 431.042 | 287.88 ± 517.901 |
| Week 8 | 178.31 ± 443.346 | 304.74 ± 521.535 |
| Week 12 | 203.22 ± 454.296 | 320.40 ± 526.783 |
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.
| Percentage of PNH Red Blood Cells | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 33.63 ± 18.149 | 49.13 ± 29.701 |
| Week 2 | 54.95 ± 12.943 | 65.65 ± 29.279 |
| Week 4 | 65.88 ± 12.907 | 73.74 ± 24.616 |
| Week 8 | 79.62 ± 14.308 | 85.06 ± 16.381 |
| Week 12 | 82.87 ± 11.903 | 91.08 ± 7.842 |
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.
| ng/mL | LNP023 25 mg Bid | LNP023 50 mg Bid | LNP023 100 mg Bid | LNP023 200 mg Bid |
|---|---|---|---|---|
| Day 29 | 1240 ± 372 | 1800 ± 368 | — | — |
| Day 57 | — | — | 2640 ± 590 | 4520 ± 1520 |
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.
| h*ng/mL | LNP023 25 mg Bid | LNP023 50 mg Bid | LNP023 100 mg Bid | LNP023 200 mg Bid |
|---|---|---|---|---|
| Day 29 | 9630 ± 3870 | 15200 ± 2390 | — | — |
| Day 57 | — | — | 19800 ± 4900 | 33300 ± 8830 |
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.
| ng/mL | LNP023 25 mg Bid | LNP023 50 mg Bid | LNP023 100 mg Bid | LNP023 200 mg Bid |
|---|---|---|---|---|
| Day 29 | 520 ± 299 | 809 ± 239 | — | — |
| Day 57 | — | — | 931 ± 460 | 1510 ± 416 |
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.
| hours | LNP023 25 mg Bid | LNP023 50 mg Bid | LNP023 100 mg Bid | LNP023 200 mg Bid |
|---|---|---|---|---|
| Day 29 | 1.50 (1.00 to 4.00) | 2.00 (1.00 to 2.00) | — | — |
| Day 57 | — | — | 1.53 (0.830 to 2.00) | 2.00 (1.00 to 4.13) |
Fibrinogen level was used as a marker associated with risk of thrombosis. Plasma was used to calculate fibrinogen levels.
| g/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 3.44 ± 0.851 | 3.50 ± 1.178 |
| Week 2 | 3.27 ± 0.935 | 2.93 ± 0.445 |
| Week 4 | 2.80 ± 0.338 | 2.78 ± 0.566 |
| Week 8 | 2.77 ± 0.399 | 3.19 ± 0.531 |
| Week 12 | 2.94 ± 0.802 | 3.09 ± 0.699 |
Prothrombin time was used as a marker associated with risk of thrombosis. Plasma was used to calculate prothrombin time.
| seconds | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 10.04 ± 0.474 | 9.84 ± 0.210 |
| Week 2 | 10.51 ± 0.426 | 10.18 ± 0.179 |
| Week 4 | 10.29 ± 0.593 | 10.22 ± 0.311 |
| Week 8 | 10.66 ± 0.665 | 10.98 ± 1.678 |
| Week 12 | 10.33 ± 0.501 | 10.13 ± 0.359 |
Activated partial thromboplastin time was used as a marker associated with risk of thrombosis. Plasma was used to calculate activated partial thromboplastin time.
| seconds | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 23.63 ± 2.280 | 23.32 ± 2.470 |
| Week 2 | 25.83 ± 2.039 | 25.66 ± 1.454 |
| Week 4 | 26.10 ± 2.156 | 26.46 ± 1.802 |
| Week 8 | 27.04 ± 2.914 | 26.84 ± 3.389 |
| Week 12 | 26.48 ± 3.396 | 24.95 ± 1.279 |
D-dimer levels were used as a marker associated with risk of thrombosis. Plasma was used to calculate D-dimer levels.
| mg fibrinogen-equivalent unit (FEU)/L | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 0.39 ± 0.236 | 0.84 ± 0.345 |
| Week 2 | 0.32 ± 0.230 | 0.49 ± 0.189 |
| Week 4 | 0.29 ± 0.199 | 0.43 ± 0.172 |
| Week 8 | 0.24 ± 0.225 | 0.36 ± 0.215 |
| Week 12 | 0.25 ± 0.184 | 0.31 ± 0.147 |
thrombin clotting time was used as a marker associated with risk of thrombosis. Plasma was used to calculate thrombin clotting time.
| seconds | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid |
|---|---|---|
| Baseline | 14.77 ± 1.994 | 14.83 ± 0.916 |
| Week 4 | 14.93 ± 0.642 | 15.58 ± 1.293 |
| Week 8 | 14.90 ± 0.624 | 15.48 ± 0.923 |
| Week 12 | 16.08 ± 1.530 | 15.35 ± 0.526 |
Collected over Adverse events were reported from first dose of study treatment until end of study treatment plus 7 days post treatment, up to a maximum duration of 115 weeks.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| LNP023 25mg Bid - Period 1 | 0/7 (0%) | 0/7 (0%) | 2/7 (28.6%) |
| LNP023 50mg Bid - Period 1 | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) |
| LNP023 100mg Bid - Period 2 | 0/7 (0%) | 0/7 (0%) | 3/7 (42.9%) |
| LNP023 200mg Bid - Period 2 | 0/5 (0%) | 0/5 (0%) | 1/5 (20%) |
| LNP023 100mg Bid - Period 3 | 0/7 (0%) | 0/7 (0%) | 4/7 (57.1%) |
| LNP023 200mg Bid - Period 3 | 0/5 (0%) | 0/5 (0%) | 4/5 (80%) |
| Event | LNP023 25mg Bid - Period 1 | LNP023 50mg Bid - Period 1 | LNP023 100mg Bid - Period 2 | LNP023 200mg Bid - Period 2 | LNP023 100mg Bid - Period 3 | LNP023 200mg Bid - Period 3 |
|---|---|---|---|---|---|---|
| HeadacheNervous system disorders | 0/7 | 3/6 | 0/7 | 0/5 | 1/7 | 1/5 |
| Abdominal discomfortGastrointestinal disorders | 0/7 | 0/6 | 0/7 | 0/5 | 2/7 | 0/5 |
| Abdominal painGastrointestinal disorders | 0/7 | 0/6 | 0/7 | 0/5 | 2/7 | 0/5 |
| PyrexiaGeneral disorders | 1/7 | 0/6 | 0/7 | 0/5 | 2/7 | 1/5 |
| Upper respiratory tract infectionInfections and infestations | 0/7 | 0/6 | 2/7 | 0/5 | 0/7 | 0/5 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/7 | 0/6 | 1/7 | 0/5 | 1/7 | 0/5 |
| EosinophiliaBlood and lymphatic system disorders | 0/7 | 0/6 | 0/7 | 0/5 | 0/7 | 1/5 |
| VertigoEar and labyrinth disorders | 0/7 | 0/6 | 0/7 | 0/5 | 0/7 | 1/5 |
| EnterocolitisGastrointestinal disorders | 0/7 | 0/6 | 0/7 | 0/5 | 0/7 | 1/5 |
| COVID-19Infections and infestations | 0/7 | 0/6 | 0/7 | 0/5 | 0/7 | 1/5 |
| Age, Continuous(years) | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid | Total |
|---|---|---|---|
| Mean | 34.4 ± 15.27 | 42.5 ± 11.98 | 38.2 ± 13.93 |
| Sex: Female, Male(Participants) | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid | Total |
|---|---|---|---|
| Female | 2 | 5 | 7 |
| Male | 5 | 1 | 6 |
| Race/Ethnicity, Customized(Participants) | LNP023 25 mg Bid/100 mg Bid | LNP023 50 mg Bid/200 mg Bid | Total |
|---|---|---|---|
| Asian | 7 | 6 | 13 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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.
Ran from Apr 2019 to primary completion in Apr 2020, 12 months.
Results were first posted in Dec 2023, 3 years 8 months after primary completion.
Of 26 industry-sponsored phase 2 interventional studies under Hemoglobinuria, Paroxysmal, half reached primary completion within 16 months of starting (the median), counting those still running; a quarter within 11 and three quarters within 25. This study's 12 months is below that.
Counting every sponsor, half of 34 studies reached it within 24 months; a quarter within 12 and three quarters within 80.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Iptacopan