A Phase 2 Open Label Pilot Study to Evaluate the Safety and Efficacy of Subcutaneously Administered ELX-02 in Patients With Alport Syndrome With Col4A5 and Col4A3/4 Nonsense Mutation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 4
- 主要终点
- Number of Participants With Adverse Events Associated With Administration of 0.75 mg/kg of ELX-02 Once Daily
研究概览
简要总结
This is a Phase 2 open label pilot study to evaluate the safety and efficacy of subcutaneously administered ELX-02 in patients with X-linked or autosomal recessive Alport Syndrome with Col4A5 and Col4A3/4 nonsense mutation.
In total, up to 8 participants, with a minimum of 3 adults, will be enrolled in the trial.
The study will be comprised of the following periods for each participant:
- a Screening period of up to 6 weeks (42 days)
- a total Treatment Period of 8 weeks (60 days)
- a safety/efficacy Follow-up Period of 12 weeks (90 days) after the last treatment The Treatment Period will be a treatment of ELX-02 0.75 mg/kg SC QD for 8 weeks.
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
- 6 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A confirmed diagnosis of X-linked or autosomal recessive Alport Syndrome with a documented nonsense mutation of Col4A5 in a male or nonsense mutation of Col4A3 or Col4A4 (male or female)
- •The nonsense mutation should be UAG or UGA
- •eGFR>60 ml/min/1.73 m2 (based on CKD-EPI for ages ≥18 and Schwartz formula for participants <18)
- •Urinary protein based on two spot urine collections [urine protein/creatinine ratio (UPCR) ≥ 500 mg/g]
- •Stable regimen of ACEi/ARB for at least 4 weeks before screening (unless there is a contraindication)
排除标准
- •History of any organ transplantation
- •Mutation consistent with autosomal dominant Alport Syndrome
- •Liver disease characterized by cirrhosis or portal hypertension. Participants with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or a total bilirubin 3.0 times the upper limit of normal (ULN) will be excluded
- •History of congestive heart failure diagnosed clinically or with documented left ventricular ejection fraction (LVEF) ≤ 40%
- •History of dialysis
研究组 & 干预措施
Open label study drug treatment
干预措施: ELX-02 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events Associated With Administration of 0.75 mg/kg of ELX-02 Once Daily
时间窗: From the time of first dosing through the end of the follow-up period, a total of 5 months
Treatment Emerging Adverse Events were defined as any adverse events with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study. Severe Treatment Emerging Adverse Event is a Treatment Emerging Adverse Events with CTCAE Grade 3 or above. Related Treatment Emerging Adverse Events is defined as a Treatment Emerging Adverse Events with a certain, probable/likely, or possible relationship to the study drug. Serious Adverse Events were Adverse Events resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening.
次要结局
- Change From Baseline in Proteinuria(From screening assessment to end of study treatment, total of 3 timepoints for results at Baseline, Week 4 and End of Treatment at Day 60.)
- Change From Baseline to End of Treatment in Collagen IV Expression (Combined Average of Alpha 3 and Alpha 4 Chains)(Baseline to End of Treatment (at Day 60))
- Change From Baseline to End of Treatment in Collagen IV Expression (Foot Process Width in Renal Biopsy)(Baseline to End of Treatment (at Day 60))
- Change From Baseline to End of Treatment in Collagen IV Expression (Filtration Slit Density in Renal Biopsy)(Baseline to End of Treatment (at Day 60))