A Prospective, Open Label, Safety and Efficacy Study of Infusions of HepaStem in Urea Cycle Disorders Pediatric Patients
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Number of subjects with anti-HLA antibody
研究概览
简要总结
This is a phase2, prospective, open label study designed to investigate the safety and efficacy of several infusions of HepaStem. This study will include 5 pediatric Urea Cycle Disorder (UCD) patients under 12 years old.
Its assessment includes all safety parameters and an efficacy assessment based on 13C tracer tests, ammonia, medication and diet changes.
HepaStem will be administered in addition to the conventional UCD treatments.
详细描述
Patient eligibility will be assessed during the Screening visit. The investigator should ensure that the chronic metabolic treatment (i.e. balance between low protein diet, supplements in amino acid mix, nitrogen scavenger and supplements in arginine and/or citrulline) of the patient is optimized for his/her metabolic condition.
During the baseline period, 3 study visits will take place at 6 weeks interval for assessing the metabolic condition and the chronic metabolic treatment of the patient.
A calculated dose based on patient's body weight will be administered via Permanent mesenteric Portal Access and Catheter for four times or a Transient Percutaneous Transhepatic Catheter for three times.
The follow-up period will start approximately 12 weeks after the first HepaStem infusion day. This period will last approximately 9 months. Study visits will take place every 1.5month, FU visit 1 to FU visit 7.
Primary Objective:
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
盲法说明
No Masking applied.
入排标准
- 年龄范围
- — 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient is a pediatric patient <12 years
- •The patients presents with one of the following UCDs. (CPS1D, OTCD, ASSD, ASLD, ARGD)
- •The patient has severe disease with impaired protein tolerance defined as: chronic protein restricted diet AND chronic treatment with at lease one nitrogen scavenger.
- •The patient shows patency of the portal vein and its branches including mesenteric veins, with normal flow velocity as confirmed by Doppler US and accessibility of the portal vein and/or affluents.
- •The patient (if capable of signing) and parents or legal representative have signed a written informed consent form.
排除标准
- •The patient presents acute liver failure.
- •The patient presents clinical or radiological evidence of liver cirrhosis.
- •The patient presents or has a history of hepatic or extrahepatic malignancy.
- •The patient has a known clinically significant cardiac malformation.
- •The patient has a personal history of venous thrombosis, or has a clinically significant abnormal value for protein S, protein C, anti-thrombin III, and/or activated Protein C Resistance (aPCR) at screening. In case of known family history, a complete coagulation work-up should be performed. in all above described cases, results need to be discussed with sponsor before enrolling the patient in the study.
- •Patient currently receiving other unapproved investigational drug or device.
- •The patient underwent previous mature liver cell or stem cell transplantation or received an organ liver transplant or received HepaStem infusion.
- •The patient has a contraindication to methylprednisolone, tacrolimus.
- •The patient has a known hypersensitivity or allergy to heparin.
- •The patient has a known hypersensitivity or allergy to the antibiotics preventing post-operative infections that are prescribed according to institutional guidelines, and no alternative prophylaxis can be found.
- •The patient had or has a renal insufficiency treated by dialysis.
- •The patient requires valproate therapy.
- •The patient has a known hypersensitivity or allergy to contrast agents (if applicable) that cannot be treated adequately.
- •The patient has a thrombosis of the portal vein or persisting impairment of anterograde portal blood flow.
- •The patient has a porto systemic shunt or fistula assessed by Doppler US or an Arantius channel or protal hypertension.
- •The site where the catheter is intended to be placed has previously suffered from venous thrombosis or vascular surgical procedures.
- •The patient has an ongoing infection or suffered from an infection in the last 2 weeks (including active EBV infection at screening). The patient may be enrolled after resolution of the infection.
- •There is any significant condition or disability that, in the investigator's opinion, may interfere with the patient's participation in the study.
结局指标
主要结局
Number of subjects with anti-HLA antibody
时间窗: up to 12 months after the first infusion
Safety evaluation in terms of de novo detection of donor-specific circulating anti-HLA antibodies and/or other immune-related markers
Number of subjects with SAEs and AEs
时间窗: up to 12 months after the first infusion
Safety evaluations in terms of SAEs and clinically significant AEs related to study procedures
Hemodynamics (measurement of portal vein pressures)
时间窗: up to 12 months after the first infusion
Safety evaluation in terms of portal-vein hemodynamics
Change of ureagenesis
时间窗: at 6 months after the first infusion
Change of de novo ureagenesis at 6 months after the first infusion: absolute 13C blood urea AUC-120 min quantified with the 13C Tracer method at FU visit 3 compared with baseline evaluations.
次要结局
- Change of the level of blood ammonia(Up to 12 months after the first infusion)
- Change of chronic single amino acid intake(Up to 12 months after the first infusion)
- Change of chronic nitrogen scavenger dose(Up to 12 months after the first infusion)
- Change of ureagenesis(at 3, 9 and 12 months after the first infusion)
- Change of chronic protein intake(Up to 12 months after the first infusion)
- Evaluation of cognitive skill(Up to 12 months after the first infusion)
- Number of subjects with Metabolic decompensations(Up to 12 months after the first infusion)
- Change of relevant blood amino acids values(Up to 12 months after the first infusion)
- Evaluation of Behavior indicator(Up to 12 months after the first infusion)
- Evaluation of health-related Quality of Life (QoL) indicator(Up to 12 months after the first infusion)