A Phase II, Open-Label Study of NM8074 in Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 12
- 主要终点
- Normalization of Schistocyte levels (<1%)
研究概览
简要总结
This is a Phase II, open-label study designed to determine if intravenously administered NM8074 results in remission from TMA in treatment-naïve aHUS patients.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •Pregnant, planning to become pregnant, or nursing female subjects.
研究组 & 干预措施
Cohort 1
6 subjects will receive an intravenous (IV) infusion of NM8074 at every two weeks for a total of 7 doses
干预措施: NM8074 (Drug)
Cohort 2
6 subjects will receive weekly doses of 10 mg/kg for a total of 4 doses followed by biweekly doses at 20 mg/kg for a total of 5 doses
干预措施: NM8074 (Drug)
结局指标
主要结局
Normalization of Schistocyte levels (<1%)
时间窗: Up to Study Day 120
Change from Baseline or Percent Change from Baseline in renal function
时间窗: Up to Study Day 120
Assessed via the change from baseline or percent change from baseline in serum creatinine level.
Normalization of platelet count (≥150 x 10^9/L)
时间窗: Up to Study Day 120
Normalization of LDH levels to below ULN
时间窗: Up to Study Day 120
Change from Baseline or Percent Change from Baseline in proteinuria/creatininuria
时间窗: Up to Study Day 120
Change from Baseline or Percent Change from Baseline in Hemoglobin
时间窗: Up to Study Day 120
Change from Baseline or Percent Change from Baseline in Haptoglobin
时间窗: Up to Study Day 120
次要结局
- Time to achieve complete TMA response(Baseline through Study Day 120)
- Change from Baseline or Percent Change from Baseline in Quality of Life (QoL) Assessed via the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 Scale (QLQ- C30), Version 3.0(Baseline through Study Day 120)
- Change from Baseline or Percent Change from Baseline in eGFR (estimated glomerular filtration rate)(Baseline through Study Day 120)
- Change from Baseline or Percent Change from Baseline in blood clots(Up to Study Day 120)
- Change from Baseline or Percent Change from Baseline in the total number of plasma infusions or exchanges(Baseline through Study Day 120)
- Time to achieve higher hemoglobin from baseline(Baseline through Study Day 120)
- Change from Baseline or Percent Change from Baseline in dialysis requirement(Baseline through Study Day 120)
- Change from Baseline or Percent Change from Baseline in quality of life (QoL) Assessed via the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale, Version 4.(Baseline through Study Day 120)