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

Study Overview
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Brief Summary
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To determine whether LFG316 can induce a hematological response, as measured by reduction in hemolytic activity, in patients with PNH.

Official Title
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An Open-label Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316, an Anti-C5 Monoclonal Antibody in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Conditions
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Paroxysmal Nocturnal Hemoglobinuria PNH

Intervention / Treatment
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* Biological: LFG316
* Drug: LNP023


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between the age of 18-75 (inclusive), or 18-65 (applicable in Czech Republic) with a diagnosis of PNH prior to screening A documented PNH clone size of ≥10% by RBCs and/or granulocytes Serum LDH levels at least 1.5-fold above the upper limit of normal (ULN) at screening Negative pregnancy test for women of child bearing potential at screening Previous vaccination against Neisseria meningitidis is required at least 2 weeks prior to first dosing. Exclusion Criteria: Known or suspected hereditary complement deficiency History of recurrent meningitis, history of meningococcal meningitis despite vaccination Presence or suspicion (based on judgment of the investigator) of active bacterial infection within 2 weeks prior to first dose of LFG316, or recurrent bacterial infections Under active therapy with other agents interfering with the complement system Severe concurrent co-morbidities that are a likely caused by underlying autoimmune diseases other than PNH Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 50 days after the last dose of LFG316.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LFG316 then LNP023<br>LFG316: Treatment periods 1-3 and first 4 weeks of period 4. LNP023: Treatment Period 4 | Biological: LFG316<br>* LFG316 will be administered to all patients enrolled in the study LFG316: Treatment periods 1-3 and first 4 weeks of period 4. LNP023: Treatment Period 4<br>* Other names: LFG316 then LNP023;Drug: LNP023<br>* LNP023 will be administered in period 4 to patients who participate in period 3 of this study and are willing to join long term extension study with LNP023.<br>* Other names: LFG316 then LNP023;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum lactate dehydrogenase (LDH) levels | Changes in serum lactate dehydrogenase (LDH) levels after treatment with LFG316 | Screening, weekly for 4 weeks, every 2 weeks from week 4 to week 208, every 8 weeks from week 210 to 312 in periods 1-3, every 1 or 2 weeks from day 1 to day 57, every 4 or 8 weeks from day 85 to day 141 in period 4, and EoS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Including any clinically relevant findings related with ECG, vital signs, laboratory data after treatment with LFG316 | Participants will be monitored for AEs and SAEs for the whole duration of the study (i.e. up to 312 weeks after the first treatment for periods 1-3 and up to day 148 for period 4) | 
| AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) - Pharmacokinetics parameter | Blood draw for pharmacokinetics evaluation after treatment with LFG316 | 320 weeks: screening visit, weekly visits for 4 weeks, and every 4 weeks from week 4 to week 54, visit on weeks 80, 106 132, 158, 184 and EOS) | 
| Maximum Plasma Concentration (Cmax) - Pharmacokinetics parameter | Blood draw for pharmacokinetics evaluation after treatment with LFG316 | 320 weeks: screening visit, weekly visits for 4 weeks, and every 4 weeks from week 4 to week 54, visit on weeks 80, 106 132, 158, 184 and EOS) | 
| Time to Maximum Concentration (Tmax) - Pharmacokinetics parameter | Blood draw for pharmacokinetics evaluation after treatment with LFG316 | 320 weeks: screening visit, weekly visits for 4 weeks, and every 4 weeks from week 4 to week 54, visit on weeks 80, 106 132, 158, 184 and EOS) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PNH, LFG316, LNP023