Study of NM8074 in Patients With aHUS With Evidence of Ongoing Thrombotic Microangiopathy

The proposed study, NM8074-aHUS-401,will initially assign six (6) patients per cohort in a 2-cohort trial. In the first cohort, we will evaluate a biweekly dosing regimen whereas in the second cohort, we will evaluate a weekly dose (10 mg/kg) followed by the biweekly dose (20 mg/kg) over a 3-month period. These studies will determine if NM8074 results in remission from TMA in aHUS patients. If the study shows efficacy in aHUS, additional patients may be added per cohort.

Inclusion criteria

• Patients ≥ 18 years at the time of consent
• Patients with evidence of resistant or relapsed complement-mediated aHUS with symptoms of Thrombocytopenia, hemolysis, ongoing Thrombotic Microangiopathy and acute kidney injury.
• Evidence of ongoing Thrombotic Microangiopathy which includes Haptoglobin <LLN or undetectable and/or presence of schistocytes
• Acute kidney injury (proteinuria/creatinuria > ULN and/or reduced eGFR)
• Platelets less than 150,000 per microliter (Thrombocytopenia)
• Anemia (Hemoglobin ≤10 g/dL) due to hemolysis
• Lactate dehydrogenase (LDH) level ≥ 1.5 times the upper limit of normal (xULN) during Screening
• All patients must be vaccinated prior to dosing with MenACWY Menactra® polysaccharide diphtheria toxoid conjugate vaccination against Neisseria meningitidis serogroups A, C, Y, and W-135 and MenB meningococcal serogroup B vaccine (Bexsero®). If the window of vaccination is short, then patients will be prophylactically treated with appropriate antibiotics
• Willing 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.
• Male patients and partners of child-bearing potential must agree to use contraceptives and male patients must agree to refrain from donating sperm for the duration of the study.
• Female partners of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must have a negative pregnancy test at screening and must agree to use highly effective methods of contraception during dosing and for 1 month after stopping the investigational drug.

Exclusion criteria

• History of bone marrow, hematopoietic stem cell, or solid organ transplantation
• Treatment with complement blockers
• Patients with infections
• HUS due to ADAMTS-13 deficiency (<5%)
• Kidney disease other than aHUS
• Chronic dialysis (hemo or peritoneal)
• Liver disease or other major autoimmune diseases
• Typical HUS (Shiga toxin +)
• Known Systemic Lupus Erythematosus (SLE), Systemic Sclerosis, or antiphospholipid antibody positivity or syndrome
• History of currently active primary or secondary immunodeficiency
• Currently active systemic infection or suspicion of active bacterial, viral, or fungal infection within 2 weeks prior to first dose, or history of unexplained, recurrent bacterial infections
• Has a currently active or known history of meningococcal disease or N. meningitidis infection
• Severe concurrent co-morbidities not amenable to active treatment, e.g., patients with severe kidney disease (CKD stage 4, chronic dialysis)
• Females who have a positive pregnancy test result at Screening or on Day 1.
• Pregnant, planning to become pregnant, or nursing female subjects.