Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Inclusion Criteria:

• At least 18 years of age
• Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
• On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3months prior to the Screening Visit
• Hb <10.5 g/dL at the Screening Visit
• Absolute reticulocyte count > 1.0x ULN at the Screening Visit
• Platelet count of >50,000/mm3 at the Screening Visit
• Absolute neutrophil count >500/mm3 at the Screening Visit
• Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcuspneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documentedevidence exists that subjects are non-responders to vaccination as evidenced by titersor display titer levels within acceptable local limits
• Women of child-bearing potential (WOCBP) must have a negative pregnancy test at theScreening and Day -28 Visit (Run-in Period) and must agree to use protocol definedmethods of contraception for the duration of the study and 90 days after their lastdose of study drug
• Males must agree to use protocol defined methods of contraception and agree to refrainfrom donating sperm for the duration of the study and 90 days after their last dose ofstudy drug
• Willing and able to give informed consent
• Willing and able to self-administer APL-2 (administration by caregiver will beallowed)
• Have a body mass index (BMI) ≤35.0 kg/m2

Exclusion Criteria:

• Active bacterial infection that has not resolved within 14 week of Day -28 (first doseof APL-2)
• Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4weeks prior to Screening
• Hereditary complement deficiency
• History of bone marrow transplantation
• History or presence of hypersensitivity or idiosyncratic reaction to compounds relatedto the investigational product or SC administration
• Participation in any other investigational drug trial or exposure to otherinvestigational agent within 30 days or 5 half-lives (whichever is longer)
• Currently breast-feeding women
• Inability to cooperate or any condition that, in the opinion of the investigator,could increase the subject's risk of participating in the study or confound theoutcome of the study This study includes cardiac safety evaluations. The following cardiac eligibility criteriaare necessary to avoid confounding the cardiac safety outcomes:
• History or family history of Long QT Syndrome or torsade de pointes, unexplainedsyncope, syncope from an uncorrected cardiac etiology, or family history of suddendeath
• Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty,stroke, cardiac surgery, or hospitalization for congestive heart failure within 3months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2
• QTcF > 470 ms, PR > 280 ms
• Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete HeartBlock unless the patient has an implanted pacemaker or implantable cardiacdefibrillator (ICD) with backup pacing capabilities
• Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetronor pentamidine at screening
• Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stabledose for less than 3 weeks prior to dosing
• Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than oneweek prior to the first dose of study medication (must have a repeat screening ECGafter one week of prophylactic antibiotics with QTcF < 470 ms)