A Phase 2, single arm study of Safety and Efficacy of Coversin in adult aHUS subjects
试验速览
- 阶段
- 2 期
- 状态
- Other
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- Proportion of subjects with Normal Platelet count at Day 180
研究概览
简要总结
Atypical Haemolytic Uraemic Syndrome (aHUS) is a rare, genetic, progressive and life threatening disease which results from uncontrolled activation of the complement system leading to thrombotic microangiopathy (TMA) and subsequently severe renal damage, loss of kidney function and sometimes death. The current standard of care in India is plasma exchange or plasma infusion, dialysis, and kidney transplantation. A humanized monoclonal antibody which inhibits the complement system by binding on C5 molecule has shown to be effective in the treatment of aHUS and has been approved for the treatment of aHUS in many countries globally since 2011 but is not available to patients in India currently. Eculizumab has been shown to improve the morbidity and mortality in aHUS patients significantly.
rVA576 is a naturally derived compound (from tick saliva) that also acts as a complement inhibitor but binds to different site domain on C5 molecule. It is designed to be self-administered via a daily subcutaneous injection.
The current standard of care in India for aHUS treatment is plasma exchange and dialysis. These treatment options are associated with significant morbidity and mortality and a complement inhibitor therapy has potential to change the treatment pathway for aHUS patients in India. Compared to standard of care of plasma exchange and dialysis, the rVA576 as a terminal complement inhibitor is hoped to improve morbidity and mortality in aHUS patients
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •18 years and older at the time of consent
- •LDH at screening or at the onset of the current aHUS episode was ≥ 1.5 ULN
- •Platelet count at screening <150 X 109/ L
- •Evidence of AKI as per KDIGO guidelines.
- •Males and females of childbearing potential must agree to use an adequate method of contraception.
- •Females will have a negative serum pregnancy test before entry to the study and throughout the study.
- •Women of child-bearing potential are considered to remain so following menarche until becoming post-menopausal unless permanently sterilised.
- •Permanent sterile methods include hysterectomy, bilateral salpingectomy, bilateral oophorectomy.
- •Postmenopausal state is defined as no menses for 12 months without an alternative cause.
- •The patient has given voluntary written informed consent
- •Willing to receive immunisation against Neisseria meningitidis and antibiotic prophylaxis in accordance with the KDIGO guidelines and local standard of care of the PI at each trial site
- •The patient is willing to comply with the process of preparation and self-administration of the study drug.
排除标准
- •Thrombotic Thrombocytopenic Purpura (TTP), defined as ADAMTS13 activity <10% from a historical observation (prior to initiation of PT) or as tested at the screening visit.
- •Typical HUS (known Shiga toxin + or positive EHEC culture)
- •HUS related to known HIV infection
- •Identified drug exposure-related HUS
- •HUS related to bone marrow transplant (BMT)
- •HUS related to Cobalamin (vitamin B12) deficiency
- •Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within 7 days of the screening visit and not treated with antibiotics to which the organism is sensitive
- •Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease
- •Unresolved meningococcal disease
- •Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome
- •Prior use of eculizumab (Soliris®) within 2 months of screening is prohibited
- •Exposure to any other investigational drug acting directly on the complement system within 5 half-lives of screening is prohibited
- •Chemotherapeutic agents within 3 months of enrolment in the study are prohibited
- •History of malignancy within 5 years of screening
- •Known sensitivity to the excipients of meningococcal vaccines, ciprofloxacin or any other antibiotic being administered for purposes of meningitis prophylaxis
- •Participation in other clinical trials within 4 weeks of signing the ICF
- •Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom).
结局指标
主要结局
Proportion of subjects with Normal Platelet count at Day 180
时间窗: Day 180
次要结局
- Complete TMA response with preserved renal function and improved renal function. Proportion of subjects with TMA event free status. Time to complete TMA response with improved renal function. Platelet mean count change.Proportion of subjects with Hematologic Normalization.Proportion of subjects with normalisation of platelet count.Proportion of subjects with improvement in renal function.Reduction in requirement for Dialysis. Major Adverse Vascular Events (MAVE) rate.Safety for Coversin.(Day 30, Day 60, Day 90, Day120, Day 150, Day 180.)