Study of NM8074 in Soliris-Treated Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

The proposed study, NM8074-PNH-101, is a phase II, open-label, multi-dose, unicenter trial to evaluate the safety and efficacy of NM8074 in Soliris-treated PNH subjects.

Inclusion Criteria:Male or female patients ≥ 18 years at the time of consentConfirmation of PNH diagnosis by flow cytometry evaluation of red blood cells (RBCs) and white blood cells (WBCs), with granulocyte or monocyte clone size of ~5%Presence of one or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia: hemoglobin < 10 g/dL, history of a major adverse vascular event (including thrombosis), dysphagia, erectile dysfunction, PNH-mediated pRBC transfusionsPNH patients must be undergoing treatment with Soliris for at least 3 months prior to screening, and must have a lactate dehydrogenase (LDH) level ≥ 1.5 times the upper limit of normal (ULN) during ScreeningWilling and able to understand and complete informed consent procedures, including signing and dating the informed consent form (ICF), and comply with the study visit schedule.Female subjects of childbearing potential must have a negative pregnancy test at Screening, and must not be planning pregnancy throughout the extent of the study termFemale subjects of child-bearing potential and all male subjects must agree to use of effective contraception during studySoliris treated individuals must be able to provide documentation of vaccination against meningococcal infections.Exclusion Criteria:Platelet count < 30,000/µL at ScreeningAbsolute neutrophil count (ANC) < 500 cells/µL at ScreeningBody weight < 85 lbs. (38 kg) at ScreeningEstimated glomerular filtration rate of < 30 mL/min/1.73m2 based on modification of diet in renal disease (MDRD) equation, creatinine clearance, or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) at ScreeningElevation of liver function tests: alanine aminotransferase (ALT) > 2xULN or direct bilirubin and alkaline phosphatase (ALP) both > 2xULNHas a known history of meningococcal disease or N. meningitidis infectionHas an immunological disorder, such as, but not limited to, human immunodeficiency virus (HIV) infection (as evident by HIV-1 or HIV-2 antibody titer) or any acute or chronic infection including, but not limited to, hepatitis B virus (HBV) or hepatitis C virus (HCV)Currently active systemic infection or suspicion of active bacterial, viral, or fungal infection that requires antibiotic, antifungal, antiparasitic, or antiviral mediationsTemperature > 38°C for more than two weeks prior to screeningHistory of bone marrow or solid organ transplantationPregnant, planning to become pregnant, or nursing female subjectsRecent surgery requiring general anesthesia within the 2 weeks prior to Screening, or expected to have surgery requiring general anesthesia during the 12-week treatment periodActive malignancy requiring surgery, chemotherapy, or radiation within the prior 12- months (subjects with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12-months prior to screening with no detectable recurrences are allowed)History of any significant major medical conditions (cardiac, pulmonary, renal, e endocrine, or hepatic), or psychiatric disorder that, in the opinion of the Investigator, would make the subject unsuitable for participation in the studyPNH patients currently under complement blocker treatments other than SolirisConcomitant use of anticoagulants is prohibited, if not on a stable regimen for at least 2 weeks prior to Day 1Participation in any experimental small molecule or non-antibody therapy within 60 days prior to dosing on Day 1 (participation in observational studies and/or registry studies is permitted)Known or suspected history of illegal recreational drug or alcohol abuse within 1 year prior to start of screeningHypersensitivity or history of allergy to excipients in NM8074 formulationUnable or unwilling to comply with the requirements of the study