NCT03205995终止3 期
A Phase 3 Study to Evaluate the Safety and Efficacy of OMS721 for the Treatment of Atypical Hemolytic Uremic Syndrome (aHUS) in Adults and Adolescents
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Platelet Count (10^9 Platelets/L) Change From Baseline at Week 26
研究概览
简要总结
The purpose of this study is to evaluate the platelet count change from baseline and safety of OMS721 (narsoplimab) in adults and adolescents with atypical hemolytic uremic syndrome (aHUS). The study will also evaluate pharmacokinetics (PK), pharmacodynamics (PD), and anti-drug antibody response (ADA).
详细描述
This is a Phase 3, uncontrolled, open-label study to evaluate the effect of OMS721 in subjects with aHUS. The primary outcome to be measured is platelet count change from baseline. The secondary outcomes to be measured are other efficacy measures, safety, PK, PD, and immunogenicity (i.e., presence of anti-drug antibody [ADA] response. Subjects with plasma therapy-resistant aHUS and plasma therapy-responsive aHUS will be eligible. The efficacy endpoints, including the primary efficacy endpoint, may not be relevant for plasma therapy-responsive subjects because these subjects may enter the study with normal markers of aHUS activity due to successful treatment with plasma therapy. Therefore, efficacy analyses will be performed separately in the plasma therapy-resistant and plasma therapy responsive subjects. The principal efficacy analyses will be the analyses in the plasma therapy resistant cohort and efficacy analyses of the plasma therapy-responsive cohort will be supportive. Safety analyses will be conducted in all subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are age >= 12 years old at screening (Visit 1).
- •Have a primary aHUS, diagnosed clinically, and have ADAMTS13 activity > 5% in plasma. Participants are eligible with or without a documented complement mutation or anti-CFH antibody. Participants are categorized according to their response to plasma therapy (plasma exchange or plasma infusion):
- •Plasma therapy-resistant aHUS participants must have all of the following:
- •Screening platelet count < 150,000/μL despite at least four plasma therapy treatments in a 7-day period prior to screening
- •Evidence of microangiopathic hemolysis (at least one of:
- •presence of schistocytes,
- •serum LDH > 1.5 times upper limit of normal (ULN), and
- •haptoglobin < LLN)
- •Serum creatinine > ULN
- •Plasma therapy-responsive aHUS participants must have all of the following:
- •Have a documented history of requiring plasma therapy to prevent aHUS exacerbation defined as all of the following:
- •decrease in platelet count > 25% when plasma therapy frequency has been decreased (including discontinuation of plasma therapy)
- •LDH > 1.5 times ULN when plasma therapy frequency has been decreased (including discontinuation of plasma therapy)
- •Have received plasma therapy at least once every 2 weeks at an unchanged frequency for at least 8 weeks before first dose of OMS721
- •If sexually active and of childbearing potential, must agree to practice a highly effective method of birth control until the end of the study, defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner.
- •Do not have access to eculizumab treatment, have not derived therapeutic benefit from eculizumab treatment, or have not been able to tolerate eculizumab treatment.
排除标准
- •Have STEC-HUS.
- •Have a positive direct Coombs test.
- •Have a history of hematopoietic stem cell transplant.
- •Have HUS from an identified drug.
- •History of vitamin B12 deficiency-related HUS.
- •History of Systemic Lupus Erythematosus.
- •History of antiphospholipid syndrome.
- •Active cancer or history of cancer (except non-melanoma skin cancers) within 5 years of screening.
- •Have been on hemodialysis or peritoneal dialysis for ≥ 12 weeks.
- •Have an active systemic bacterial or fungal infection requiring systemic antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed).
- •Baseline resting heart rate < 45 beats per minute or > 115 beats per minute.
- •Baseline QTcF > 470 milliseconds.
- •Have malignant hypertension (diastolic blood pressure [BP] > 120 mm Hg with bilateral hemorrhages or "cotton-wool" exudates on funduscopic examination).
- •Have a poor prognosis with a life expectancy of less than three months in the opinion of the Investigator.
- •Are pregnant or lactating.
- •Have received treatment with an investigational drug or device within four weeks of the screening visit.
- •Have abnormal liver function tests defined as ALT or AST > five times ULN.
- •Have HIV infection.
- •History of cirrhosis of the liver.
- •Are an employee of Omeros, an Investigator, a study staff member, or their immediate family member.
- •Have a known hypersensitivity to any constituent of the product.
- •Presence of any condition that the Investigator believes would put the subject at risk or confound the interpretation of the data.
- •Have previously completed treatment in an OMS721study.
- •Have received intravenous immunoglobulin (IVIG) treatment within 8 weeks of screening visit.
- •Have received rituximab within 24 weeks of screening visit.
研究组 & 干预措施
OMS721 (narsoplimab)
Experimental
Administration of OMS721 (narsoplimab)
干预措施: OMS721 (narsoplimab) (Biological)
结局指标
主要结局
Platelet Count (10^9 Platelets/L) Change From Baseline at Week 26
时间窗: Week 26
The primary outcome to be measured is platelet count change from baseline.
次要结局
- Safety as Measured by Incidences of Adverse Events, Vital Signs, ECG, and Clinical Laboratory Tests(Pre-dose and up to 771 days post-dose)
- Thrombotic Microangiopathies (TMA) Response(26 weeks)
- Change From Baseline in Haptoglobin (mg/dL)(26 weeks)
- TMA Event-free Status(26 weeks)
- Increase in Estimated Glomerular Filtration Rate (eGFR)(26 weeks)
- Hematological Normalization(26 weeks)
- TMA Remission(26 weeks)
- Incidence of Antidrug Antibodies (ADA)(771 days post-dose)
- Change From Baseline in Serum Creatinine (mg/dL)(26 weeks)
- Change From Baseline in Serum LDH (U/L)(26 weeks)
- Pharmacokinetics (PK): Trough Plasma Concentration, Lower Limit of Quantification (LLOQ)(Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (RT) (if occurs): RT Days 1-4; Follow-Up at Day 771)
- Pharmacokinetics (PK): Maximum Plasma Concentrations (Cmax)(Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771)
- Pharmacokinetics (PK): Area Under Time-concentration Curve (AUC)(Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771)
- Pharmacodynamics (PD): Inhibition of C3 Activity (%)(Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771)
- Pharmacodynamics (PD): Inhibition of C4 Activity (%)(Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771)
研究者
研究点 (1)
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