Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.

2. Male and female patients at least 18 years old at baseline.

3. Diagnosis of active PNH based on documented clone size of ≥10% by RBCs and/orgranulocytes, measured by GPI-deficiency on flow cytometry (screening or medicalhistory data acceptable).

4. LDH values > 1.5 x upper limit of the normal range (ULN) for at least 3 measurementsover a maximum of 8 weeks prior to Day 1 (Screening, baseline or medical historydata acceptable).

5. Hemoglobin level < 10.5 g/dL at Baseline.

6. For Period 3 of the study, patients who as per judgment of Investigator benefit fromLNP023 treatment based on reduced hemolytic parameters as compared to Screening andBaseline.

7. Vaccinations against N. meningitidis, S. pneumoniae and H. influenzae is required atleast 4 weeks prior to first dosing with LNP023 (existing vaccinations shouldprovide effective titers at time of LNP023 treatment start). If LNP023 treatment hasto start earlier than 4 weeks post vaccination, prophylactic antibiotic treatmentmust be initiated.

8. Able to communicate well with the investigator, to understand and comply with therequirements of the study. -

Exclusion Criteria:

1. Participation in any other investigational drug trial or use of otherinvestigational drugs at the time of enrollment, or within 5 elimination half-livesof enrollment, or within 30 days, whichever is longer; or longer if required bylocal regulations.

2. Patients treated with eculizumab or any other complement inhibitor less than 3months prior to study Day 1

3. Known or suspected hereditary or acquired complement deficiency.

4. History of currently active primary or secondary immunodeficiency.

5. History of splenectomy.

6. History of bone marrow/ hematopoietic stem cell or solid organ transplants (e.g.heart, lung, kidney, liver).

7. Evidence of malignant disease, or malignancies diagnosed within the previous 5years.

8. Patients with laboratory evidence of bone marrow failure (reticulocytes < 60x10E9/L,or platelets < 50x10E9/L or neutrophils < 1x10E9/L) verified both at screening andbaseline.

9. History of recurrent meningitis, history of meningococcal infections despitevaccination, as verified at both screening and baseline.

10. Presence or suspicion (based on judgment of the investigator) of active infectionwithin 2 weeks prior to first dose of LNP023, or history of severe recurrentbacterial infections.

11. A positive HIV, Hepatitis B (HBV) or Hepatitis C (HCV) test result at screening.

12. Patients on immunosuppressive agents such, as but not limited to, cyclosporine,tacrolimus, mycophenolate or mycophenolic acid, cyclophosphamide, methotrexate or IVimmunoglobulins, less than 8 weeks prior to first treatment with LNP023, unless on astable regimen for at least 3 months prior to first LNP023 dose.

13. Systemic corticosteroids unless on a stable dose for at least 4 weeks beforerandomization.

14. Severe concurrent co-morbidities not amenable to active treatment; e.g., patientswith severe kidney disease (CKD stage 4, dialysis), advanced cardiac disease (NYHAclass IV), severe pulmonary arterial hypertension (WHO class IV), or unstablethrombotic event, as judged by the investigator, both at screening and baseline (unless baseline was skipped).

15. Any medical condition deemed likely to interfere with the patient's participation inthe study, or likely to cause serious adverse events during the study.

16. History of hypersensitivity to the study treatment or its excipients or to drugs ofsimilar chemical classes.

17. Female patients who are pregnant or breastfeeding, or intending to conceive duringthe course of the study.

18. Women of child-bearing potential, defined as all women physiologically capable ofbecoming pregnant, unless they are using highly effective methods of contraceptionduring dosing and for 1 week after stopping of investigational drug