NCT04861259进行中（未招募）3 期
A Phase III, Multicenter, Single-Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 83
- 试验地点
- 85
- 主要终点
- Percentage of Participants with Complete Thormbotic Microangiopathy Response (cTMAr)
研究概览
简要总结
This study aims to evaluate the efficacy and safety of crovalimab in adult and adolescent participants with aHUS.
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
- •Body weight >= 40 kg at screening.
- •Vaccination against Neisseria meningitidis serotypes A, C, W, and Y; vaccination against serotypes B, according to national vaccination recommendations.
- •Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae, according to national vaccination recommendations.
- •For participants continuing to receive other therapies concomitantly with crovalimab (e.g., immunosuppressants, corticosteroids, mammalian target of rapamycin inhibitor (mTORi) , or calcineurin inhibitors): stable dose for >=28 days prior to screening and up to the first crovalimab administration.
- •For female participants of childbearing potential: an agreement to remain abstinent or use contraception.
- •Female participants of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of crovalimab.
- •Participants with a prior kidney transplant are eligible if they have a known history of complement-mediated aHUS prior to the kidney transplant.
- •Onset of initial TMA presentation within 28 days prior to the first dose of crovalimab (for Naive Cohort only).
- •Documented treatment with either eculizumab or ravulizumab (for Switch Cohort only).
- •Clinical evidence of response to a C5 inhibitor (for Switch Cohort only).
- •Known C5 polymorphism (for C5 SNP Cohort only).
- •Poorly controlled TMA following treatment with another C5 inhibitor (for C5 SNP Cohort only).
排除标准
- •TMA associated with non-aHUS related renal disease.
- •Positive direct Coombs test.
- •Chronic dialysis within 90 days prior to first crovalimab administration and/or end stage renal disease.
- •Identified drug exposure-related TMA.
- •Presence or history of a condition that could trigger TMA, such as malignancy, bone marrow or organ transplant (other than kidney transplant) or autoimmune disease.
- •History of a kidney disease, other than aHUS.
- •History of Neisseria meningitidis infection within 6 months of study enrollment.
- •Known or suspected immune deficiency (e.g., history of frequent recurrent infections).
- •Positive Human Immunodeficiency Virus (HIV) test.
- •Active systemic bacterial, viral, or fungal infection within 14 days before first crovalimab administration
- •Presence of fever (>= 38°C)
- •Multi-system organ dysfunction or failure.
- •Recent intravenous immunoglobulin (IVIg) treatment.
- •Pregnant or breastfeeding or intending to become pregnant.
- •Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within five half lives of that investigational product, whichever is greater.
- •Recent use of tranexamic acid.
- •Current or previous treatment with a complement inhibitor (for Naive Cohort only).
- •First initiation of plasma exchange/plasma infusions (PE/PI) should not be more than 28 days prior to first crovalimab administration (for Naive Cohort only).
- •Last PE/PI completed less than 2 hours prior to first crovalimab administration (for Naive Chorot only).
- •Receiving PE/PI within 8 weeks of the first crovalimab administration (Switch Cohort only).
- •Positive for active Hepatitis B and C infection (HBV/HCV) (for Switch Cohort and C5 SNP Cohort participants who recently received C5 inhibitor treatment).
- •Cryoglobulinemia at screening (for Switch Cohort and C5 SNP Cohort participants who recently received C5 inhibitor treatment).
- •Diagnosis of condition leading to non-aHUS TMA: Thrombotic Thrombocytopenic Purpura (TTP), Shiga Toxin producing Escherichia Coli (STEC)
- •TMA, Pneumococcal HUS, TMA secondary to cobalamin C defect and TMA related to a known DGKE nephropathy.
研究组 & 干预措施
Crovalimab
Experimental
Participants will be enrolled in three cohorts: [1] Naive Cohort - participants who have not been previously treated with complement inhibitor therapy; [2] Switch Cohort - participants who switch to crovalimab from another Complement Component 5 (C5) inhibitor and [3] C5 Single Nucleotide Polymorphism (C5 inhibitor) Cohort - participants with documented C5 polymorphism.
干预措施: Crovalimab (Drug)
结局指标
主要结局
Percentage of Participants with Complete Thormbotic Microangiopathy Response (cTMAr)
时间窗: Baseline up to Week 25 (after 24 weeks on treatment)
次要结局
- Percentage of Participants with >=25% Decrease in Serum Creatinine (Naive Cohort only)(Baseline up to Week 25 (after 24 weeks on treatment))
- Change from Baseline in Dialysis Status(Baseline up to Week 25 (after 24 weeks on treatment))
- Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)(Baseline up to Week 25 (after 24 weeks on treatment))
- Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) Stage(Baseline up to Week 25 (after 24 weeks on treatment))
- Observed Value in Platelet Count(Baseline up to Week 25 (after 24 weeks on treatment))
- Observed Value in Lactate Dehydrogenase (LDH)(Baseline up to Week 25 (after 24 weeks on treatment))
- Observed Value in Hemoglobin(Baseline up to Week 25 (after 24 weeks on treatment))
- Change from Baseline in Platelet Count(Baseline up to Week 25 (after 24 weeks on treatment))
- Change from Baseline in Lactate Dehydrogenase (LDH)(Baseline up to Week 25 (after 24 weeks on treatment))
- Change from Baseline in Hemoglobin(Baseline up to Week 25 (after 24 weeks on treatment))
- Mean Change From Baseline in Fatigue (in Adult Participants only)(Baseline up to Week 25 (after 24 weeks on treatment))
- Percentage of Participants with Platelet Count >= Lower Limits of Normal (LLN) (Naive Cohort only)(Baseline up to Week 25 (after 24 weeks on treatment))
- Percentage of Participants with Normalization of LDH (i.e. =< Upper Limit of Normal (ULN)) (Naive Cohort only)(Baseline up to Week 25 (after 24 weeks on treatment))
- Time to cTMAr (Naive Cohort only)(Up to 8 years)
- Duration of cTMAr (Naive Cohort only)(Up to 8 years)
- Percentage of Participants with Ongoing cTMAr (Naive Cohort only)(At Week 25)
- Percentage of Participants with Maintained Thrombotic Microangiopathy Control (mTMAc) (Switch Cohort only)(Baseline up to Week 25 (after 24 weeks on treatment))
- Percentage of Participants with Adverse Events (AEs)(Up to 8 years)
- Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, Malignant Hypertension (Including Malignant Renal Hypertension) and Infections (Including Meningococcal Meningitis)(Up to 8 years)
- Number of Participants with AEs Leading to Study Drug Discontinuation(Up to 8 years)
- Percentage of Participants with Clinical Manifestations of Drug-Target-Drug Complex (DTDC) Formation Amongst Those Participants who Switched to Crovalimab Treatment From Eculizumab Treatment or Ravulizumab Treatment(Up to Week 25)
- Serum Concentrations of Crovalimab Over Time(Up to 8 years)
- Prevalence of Anti-Crovalimab Antibodies at Baseline(Baseline)
- Percentage of Participants with Anti-Crovalimab Antibodies(Up to 8 years)
- Observed value of Pharmacodynamic Markers (CH50, Free/Total C5)(Up to 8 years)
研究者
研究点 (85)
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