A Phase 2 interventional study of LFG316 and LNP023 in Paroxysmal Nocturnal Hemoglobinuria, sponsored by Novartis Pharmaceuticals. Completed at 7 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-16.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2, Interventional, and Treatment
The purpose of this study was to determine whether LFG316 can induce a hematological response, as measured by reduction in hemolytic activity, in patients with paroxysmal nocturnal hemoglobinuria (PNH).
The study consisted of a 60-day screening period to assess eligibility and conduct vaccinations if required (for all patients not previously vaccinated at least 2 weeks prior to first dosing or if prior vaccination cannot be confirmed) and 4 treatment periods as follows. During the treatment period 1 (Days 1 to 29), all patients received infusions of LFG316 every 14 days. Following assessment of efficacy (hemolytic activity by serum LDH) at the end of treatment period 1, patients entered the optional 48-week treatment period 2 and continued LFG316 infusions every 14 days. At the end of treatment period 2, LFG316-responsive patients (assessed based on the investigator's judgment) were allowed to enter an additional extension period of up to 260 weeks (treatment period 3) in which they continued to receive LFG316 every 14 days. Period 4, which allowed patients to switch to LNP023, lasted approximately 21 weeks. During the first 4 weeks, patients continued to receive LFG316 in addition to oral administration of LNP023. After 4 weeks, patients discontinued LFG316 and continued with LNP023 monotherapy for approximately 16 weeks (+/- 28 days). Patients who participated in period 4 could join the long-term extension study CLNP023C12001B (NCT04747613) as soon as their eligibility was confirmed and study CLNP023C12001B was open to receive patients. There was no LNP023 treatment gap between the studies.
As per strategic decision, further development of LFG316 was terminated in favor of LNP023, Novartis offered patients enrolled in study CLFG316X2201 a conversion from LFG316 to LNP023, aiming to provide uninterrupted treatment for these PNH patients. The CLFG316X2201 trial was not a terminated study.
191 studies on the registry are indexed under Hemoglobinuria, Paroxysmal; 49 are open to participants now.
This study's enrollment of 10 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.
Counted across the registry records on this site, refreshed daily.
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.
Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Patients included in this study after protocol amendment 6 were also to fulfill the following:
To be carriers of the C5 gene minor variants as defined by nucleic acid changes that lead to amino acid exchanges in position p.Arg885.
Additional inclusion criteria for period 4
Exclusion criteria:
Either one of the following laboratory abnormalities at screening:
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.
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.
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.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
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.
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.
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.
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.
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.
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.
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.
During treatment periods 1 to 3, the regimen included LFG316 at a dosage of 20 mg/kg administered as an intravenous (i.v.) infusion biweekly. In treatment period 4, the patients were given: * LFG316 at a dosage of 20 mg/kg as an i.v. infusion every two weeks for four weeks, amounting to two infusions in total. * LNP023 at a dose of 200 mg administered orally twice daily (b.i.d.) for approximately 20 weeks, with four 50 mg capsules taken at each administration.
Biological: LFG316 · Drug: LNP023
LFG316 20 mg/kg was administered to all patients enrolled in the study: * Treatment Periods 1 to 3: LFG316 20 mg/kg as i.v. infusion every 2 weeks * Treatment Period 4: LFG316 20 mg/kg as i.v. infusion every 2 weeks for 4 weeks (total 2 infusions).
Treatment Period 4: LNP023 200 mg b.i.d. for approximately 20 weeks. Four capsules (each 50 mg) were administered each time study medication was taken.
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate
The primary efficacy variable for assessing the effect of LFG316 over the first 4 weeks of treatment was response rate where a patient was considered a responder if the percentage reduction from baseline in serum lactate dehydrogenase (LDH) was at least 60% at any time up to and including week 4 for that patient.
Time frame: Overall (Up to Week 4), Period 1 Day 8, Period 1 Day 15, Period 1 Day 22, Period 1 Day 29
Percentage Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels Over the Entire Treatment Period
Lactate dehydrogenase (LDH) levels were measured in serum samples and the percentage change from baseline was calculated. For serum LDH, baseline was the average of all pre-dose measurements.
Time frame: Baseline, Period 1 Day 29 (end of Treatment Period 1), Period 2 Day 365 (end of Treatment Period 2), Period 3 Day 1429 (end of Treatment Period 3), Period 4 Day 141 (end of Treatment Period 4)
Area Under the Concentration-time Curve (AUC) From Time Zero to the Last Measurable Serum Concentration Sampling Time (0-tlast) for LFG316
Venous whole blood samples were collected for activity-based pharmacokinetics characterization of LFG316. Pharmacokinetic parameters were determined using non-compartmental methods based on LFG316 concentrations in serum. AUC (0-tlast) was summarized using descriptive statistics.
Time frame: Pre-infusion and 2 hours after the end of infusion on Period 1 Day 1.
Maximum Observed Serum Concentration (Cmax) for LFG316
Venous whole blood samples were collected for activity-based pharmacokinetics characterization of LFG316. Pharmacokinetic parameters were determined using non-compartmental methods based on LFG316 concentrations in serum. Cmax was summarized using descriptive statistics.
Time frame: Pre-infusion and 2 hours after the end of infusion on Period 1 Day 1.
Time to Reach Maximum Serum Concentration (Tmax) for LFG316
Venous whole blood samples were collected for activity-based pharmacokinetics characterization of LFG316. Pharmacokinetic parameters were determined using non-compartmental methods based on LFG316 concentrations in serum. Tmax was summarized using descriptive statistics. Actual sampling times were used for the calculation of PK parameters.
Time frame: Pre-infusion and 2 hours after the end of infusion on Period 1 Day 1.
LFG316 Serum Concentration
The concentration of total LFG316 in serum was determined using Liquid chromatography/mass spectroscopy (LC/MS assay) and summarized using descriptive statistics.
Time frame: Period 1 Day 1 (predose (trough), post-dose), Period 2 Day 337 (predose), Period 3 Day 1289 (predose)
10 participants were enrolled at 7 sites in 3 countries.
| Milestone | LFG316 Then LNP023 |
|---|---|
| Started | 10 |
| Completed | 9 |
| Not completed | 1 |
| Withdrew: Withdrawal by subject | 1 |
| Milestone | LFG316 Then LNP023 |
|---|---|
| Started | 9 |
| Completed | 9 |
| Not completed | 0 |
The primary efficacy variable for assessing the effect of LFG316 over the first 4 weeks of treatment was response rate where a patient was considered a responder if the percentage reduction from baseline in serum lactate dehydrogenase (LDH) was at least 60% at any time up to and including week 4 for that patient.
| Participants | LFG316 Then LNP023 |
|---|---|
| Overall (Up to Week 4) — Responder | 10 |
| Overall (Up to Week 4) — Non Responder | 0 |
| Period 1 Day 8 — Responder | 6 |
| Period 1 Day 8 — Non Responder | 4 |
| Period 1 Day 15 — Responder | 9 |
| Period 1 Day 15 — Non Responder | 1 |
| Period 1 Day 22 — Responder | 9 |
| Period 1 Day 22 — Non Responder | 1 |
| Period 1 Day 29 — Responder | 9 |
| Period 1 Day 29 — Non Responder | 1 |
Lactate dehydrogenase (LDH) levels were measured in serum samples and the percentage change from baseline was calculated. For serum LDH, baseline was the average of all pre-dose measurements.
| % change from baseline in serum LDH | LFG316 Then LNP023 |
|---|---|
| Period 1 Day 29 | -78.35 ± 11.190 |
| Period 2 Day 365 | -78.56 ± 11.550 |
| Period 3 Day 1429 | -81.65 ± 8.138 |
| Period 4 Day 141 | -78.69 ± 9.288 |
Venous whole blood samples were collected for activity-based pharmacokinetics characterization of LFG316. Pharmacokinetic parameters were determined using non-compartmental methods based on LFG316 concentrations in serum. AUC (0-tlast) was summarized using descriptive statistics.
| hour*microgram/milliliter (h*µg/mL) | LFG316 Then LNP023 |
|---|---|
| Area Under the Concentration-time Curve (AUC) From Time Zero to the Last Measurable Serum Concentration Sampling Time (0-tlast) for LFG316 | 73700 ± 12600 |
Venous whole blood samples were collected for activity-based pharmacokinetics characterization of LFG316. Pharmacokinetic parameters were determined using non-compartmental methods based on LFG316 concentrations in serum. Cmax was summarized using descriptive statistics.
| nanograms per milliliter (μg/mL) | LFG316 Then LNP023 |
|---|---|
| Maximum Observed Serum Concentration (Cmax) for LFG316 | 407 ± 69.2 |
Venous whole blood samples were collected for activity-based pharmacokinetics characterization of LFG316. Pharmacokinetic parameters were determined using non-compartmental methods based on LFG316 concentrations in serum. Tmax was summarized using descriptive statistics. Actual sampling times were used for the calculation of PK parameters.
| hour (h) | LFG316 Then LNP023 |
|---|---|
| Time to Reach Maximum Serum Concentration (Tmax) for LFG316 | 2.56 (2.05 to 3.10) |
The concentration of total LFG316 in serum was determined using Liquid chromatography/mass spectroscopy (LC/MS assay) and summarized using descriptive statistics.
| nanograms per milliliter (μg/mL) | LFG316 Then LNP023 |
|---|---|
| Period 1 Day 1 (predose (trough)) | 182 ± 31.4 |
| Period 1 Day 1 (postdose) | 538 ± 80.0 |
| Period 2 Day 337 (predose) | 248 ± 55.9 |
| Period 3 Day 1289 (predose) | 313 ± 89.2 |
Collected over Adverse events were collected from first dose of LFG316 (Day 1) up to 4 weeks after last dose (Day 2213) in participants transitioning to Period 4 and up to 8 weeks after last dose (Day 2241) in participants ending participation after Period 3. In Period 4, adverse events were collected from first dose of study treatment (Day 1) up to approximately 30 days after last dose of LNP023 (Day 171).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment Periods 1 to 3: LFG316 | 0/10 (0%) | 3/10 (30%) | 10/10 (100%) |
| Treatment Period 4: LFG316 + LNP023 | 0/9 (0%) | 0/9 (0%) | 6/9 (66.7%) |
| Event | Treatment Periods 1 to 3: LFG316 | Treatment Period 4: LFG316 + LNP023 |
|---|---|---|
| BacteraemiaInfections and infestations | 1/10 | 0/9 |
| Enterocolitis viralInfections and infestations | 1/10 | 0/9 |
| InfectionInfections and infestations | 1/10 | 0/9 |
| InfluenzaInfections and infestations | 1/10 | 0/9 |
| NasopharyngitisInfections and infestations | 1/10 | 0/9 |
| Renal impairmentRenal and urinary disorders | 1/10 | 0/9 |
| Event | Treatment Periods 1 to 3: LFG316 | Treatment Period 4: LFG316 + LNP023 |
|---|---|---|
| NasopharyngitisInfections and infestations | 8/10 | 0/9 |
| HeadacheNervous system disorders | 5/10 | 1/9 |
| CystitisInfections and infestations | 4/10 | 0/9 |
| NauseaGastrointestinal disorders | 3/10 | 0/9 |
| GastroenteritisInfections and infestations | 3/10 | 0/9 |
| Herpes zosterInfections and infestations | 3/10 | 0/9 |
| Back painMusculoskeletal and connective tissue disorders | 3/10 | 0/9 |
| NeutropeniaBlood and lymphatic system disorders | 2/10 | 0/9 |
| Conjunctival haemorrhageEye disorders | 2/10 | 0/9 |
| Abdominal pain upperGastrointestinal disorders | 2/10 | 0/9 |
| Age, Categorical(Participants) | LFG316 Then LNP023 |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 9 |
| >=65 years | 1 |
| Age, Continuous(Years) | LFG316 Then LNP023 |
|---|---|
| Mean | 43.0 ± 11.68 |
| Sex: Female, Male(Participants) | LFG316 Then LNP023 |
|---|---|
| Female | 4 |
| Male | 6 |
| Race/Ethnicity, Customized(Participants) | LFG316 Then LNP023 |
|---|---|
| Caucasian | 3 |
| Asian | 7 |
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 Sep 2015 to primary completion in May 2022, 80 months.
Results were first posted in Nov 2024, 2 years 5 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 80 months is above 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 May 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tesidolumab