Trial Outcomes & Findings for Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316 in Patients With Paroxysmal Nocturnal Hemoglobinuria (NCT NCT02534909)

Last Updated: 2025-05-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Overall (Up to Week 4), Period 1 Day 8, Period 1 Day 15, Period 1 Day 22, Period 1 Day 29

Results posted on

2025-05-16

Participant Flow

10 participants were enrolled at 7 sites in 3 countries.

The study had a 60-day screening period to assess eligibility.

Participant milestones

Participant milestones
Measure	LFG316 Then LNP023 Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Treatment Period 1 to 3 (up to Week 312) STARTED	10
Treatment Period 1 to 3 (up to Week 312) COMPLETED	9
Treatment Period 1 to 3 (up to Week 312) NOT COMPLETED	1
Treatment Period 4 (20 Weeks) STARTED	9
Treatment Period 4 (20 Weeks) COMPLETED	9
Treatment Period 4 (20 Weeks) NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	LFG316 Then LNP023 Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Treatment Period 1 to 3 (up to Week 312) Withdrawal by Subject	1

Baseline Characteristics

Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316 in Patients With Paroxysmal Nocturnal Hemoglobinuria

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LFG316 Then LNP023 n=10 Participants Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	43.0 Years STANDARD_DEVIATION 11.68 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Overall (Up to Week 4), Period 1 Day 8, Period 1 Day 15, Period 1 Day 22, Period 1 Day 29

Population: The Pharmacodynamic (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data.

Outcome measures

Outcome measures
Measure	LFG316 Then LNP023 n=10 Participants Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Overall (Up to Week 4) · Responder	10 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Overall (Up to Week 4) · Non Responder	0 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Period 1 Day 8 · Responder	6 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Period 1 Day 8 · Non Responder	4 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Period 1 Day 15 · Responder	9 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Period 1 Day 15 · Non Responder	1 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Period 1 Day 22 · Responder	9 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Period 1 Day 22 · Non Responder	1 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Period 1 Day 29 · Responder	9 Participants
Percentage of Participants With Reduction in Serum Lactate Dehydrogenase (LDH) Levels Within the First 4 Weeks of LFG316 Treatment as Measured by Response Rate Period 1 Day 29 · Non Responder	1 Participants

PRIMARY outcome

Timeframe: 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)

Population: Pharmacodynamic (PD) analysis set - Only participants with a value at both Baseline and post-baseline visit included.

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.

Outcome measures

Outcome measures
Measure	LFG316 Then LNP023 n=10 Participants Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Percentage Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels Over the Entire Treatment Period Period 1 Day 29	-78.35 % change from baseline in serum LDH Standard Deviation 11.190
Percentage Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels Over the Entire Treatment Period Period 2 Day 365	-78.56 % change from baseline in serum LDH Standard Deviation 11.550
Percentage Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels Over the Entire Treatment Period Period 3 Day 1429	-81.65 % change from baseline in serum LDH Standard Deviation 8.138
Percentage Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels Over the Entire Treatment Period Period 4 Day 141	-78.69 % change from baseline in serum LDH Standard Deviation 9.288

SECONDARY outcome

Timeframe: Pre-infusion and 2 hours after the end of infusion on Period 1 Day 1.

Population: Pharmacokinetic (PK) analysis set included all patients with available PK data and no protocol deviations with relevant impact on PK data.

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.

Outcome measures

Outcome measures
Measure	LFG316 Then LNP023 n=10 Participants Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Area Under the Concentration-time Curve (AUC) From Time Zero to the Last Measurable Serum Concentration Sampling Time (0-tlast) for LFG316	73700 hourmicrogram/milliliter (hµg/mL) Standard Deviation 12600

SECONDARY outcome

Timeframe: Pre-infusion and 2 hours after the end of infusion on Period 1 Day 1.

Population: Pharmacokinetic (PK) analysis set included all patients with available PK data and no protocol deviations with relevant impact on PK data.

Outcome measures

Outcome measures
Measure	LFG316 Then LNP023 n=10 Participants Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Maximum Observed Serum Concentration (Cmax) for LFG316	407 nanograms per milliliter (μg/mL) Standard Deviation 69.2

SECONDARY outcome

Timeframe: Pre-infusion and 2 hours after the end of infusion on Period 1 Day 1.

Population: PK analysis set

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.

Outcome measures

Outcome measures
Measure	LFG316 Then LNP023 n=10 Participants Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Time to Reach Maximum Serum Concentration (Tmax) for LFG316	2.56 hour (h) Interval 2.05 to 3.1

SECONDARY outcome

Timeframe: Period 1 Day 1 (predose (trough), post-dose), Period 2 Day 337 (predose), Period 3 Day 1289 (predose)

Population: PK analysis set

The concentration of total LFG316 in serum was determined using Liquid chromatography/mass spectroscopy (LC/MS assay) and summarized using descriptive statistics.

Outcome measures

Outcome measures
Measure	LFG316 Then LNP023 n=10 Participants Treatment periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks. Treatment period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
LFG316 Serum Concentration Period 1 Day 1 (predose (trough))	182 nanograms per milliliter (μg/mL) Standard Deviation 31.4
LFG316 Serum Concentration Period 1 Day 1 (postdose)	538 nanograms per milliliter (μg/mL) Standard Deviation 80.0
LFG316 Serum Concentration Period 2 Day 337 (predose)	248 nanograms per milliliter (μg/mL) Standard Deviation 55.9
LFG316 Serum Concentration Period 3 Day 1289 (predose)	313 nanograms per milliliter (μg/mL) Standard Deviation 89.2

Adverse Events

Treatment Periods 1 to 3: LFG316

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Treatment Period 4: LFG316 + LNP023

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Periods 1 to 3: LFG316 n=10 participants at risk Treatment Periods 1 to 3: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks.	Treatment Period 4: LFG316 + LNP023 n=9 participants at risk Treatment Period 4: LFG316 20 mg/kg intravenous (i.v.) infusion every 2 weeks (Week 1 to 4) + LNP023 200 mg twice per day (b.i.d.) for approximately 20 weeks (Weeks 1 to 20)
Infections and infestations Bacteraemia	10.0% 1/10 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.	0.00% 0/9 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Infections and infestations Enterocolitis viral	10.0% 1/10 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.	0.00% 0/9 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Infections and infestations Infection	10.0% 1/10 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.	0.00% 0/9 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Infections and infestations Influenza	10.0% 1/10 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.	0.00% 0/9 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	10.0% 1/10 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.	0.00% 0/9 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Renal and urinary disorders Renal impairment	10.0% 1/10 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.	0.00% 0/9 • 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). Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 (862) 778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER