study of efficacy and safety of nm8074 in adult pnh patients who are naive to complement inhibitor therapy

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Summary: this is a phase ii, open-label study designed to evaluate the safety, efficacy, and immunogenicity of nm8074 administered intravenously to adult patients with paroxysmal nocturnal hemoglobinuria (pnh).

the proposed study will enroll a planned number of 12 treatment naïve pnh patients with amaximum of 18 pnh patients who have been diagnosed with hemolytic anemia and meet the inclusion criteria. there will be 2 cohorts with 6 to 9 patients each. patients in cohort 1 will be administered nm8074 at 20 mg/kg intravenously (iv) every 2 weeks over the treatment period. cohort 2 patients will be administered a dose of 10 mg/kg nm8074 weekly for 4 weeks followed by a 20 mg/kg dose of nm8074 administered via iv every 2 weeks for the remainder of the treatment period. this study will determine if nm8074 will provide the desired inhibition of the alternative pathway (ap).

Eligibility criteria:
inclusion criteria: * patients ≥ 18 years (males and females), weight ≥ 45 kg at the time of consent * confirmation of pnh diagnosis by flow cytometry evaluation of white blood cells (wbcs), with neutrophil, granulocyte and/or monocyte clone size of ≥10% * evidence of ongoing hemolysis * ≥1 packed red blood cell (prbc) transfusion within 12 months prior to screening * anemia (hemoglobin ≤10.5 g/dl) * 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 exclusion criteria: * history of bone marrow, hematopoietic stem cell, or solid organ transplantation * history of splenectomy * participation in any other investigational drug trial within 5 elimination half-lives of enrollment, or within 30 days, whichever is longer * subjects currently or previously under other complement inhibitor treatments less than 3 months prior to study day 1 * participants with known or suspected hereditary or acquired complement deficiency * 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 known history of meningococcal disease or n. meningitidis infection * patients on immunosuppressive agents or systemic corticosteroids less than 8 weeks prior to dosing * known medical or psychological condition(s) or risk factor that, in the opinion of the investigator, might interfere with the patient's full participation in the study, pose any additional risk for the patient, or confound the assessment of the patient or outcome of the study * severe concurrent co-morbidities not amenable to active treatment, e.g., patients with severe kidney disease (chronic kidney disease (ckd) stage 4, dialysis) * subjects currently or previously under other complement inhibitor treatments less than 3 months prior to study day 1 * pregnant, planning to become pregnant, or nursing female subjects. 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 week after stopping the investigational drug * females who have a positive pregnancy test result at screening or on day 1 * 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