None listed
Conditions
Interventions
Biological/Vaccine, Stem Cell : [Route of Administration]
Hepastem will be infused intravenously into the portal vein, either (1) via a permanent mesenteric PAC inserted surgically in an affluent of t
or (2) through a transient percutaneous transhepatic catheter inserted into the portal vein under radio guidance (i.e. in patients below 10kg.)
The choice of the administration procedure will be made
s family.
-Permanent mesenteric PAC
A permanent mesenteric portal access and catheter will be surgical placed. Then a mandatory 2 week observation for stabilixation of the patient'
s metabolic condition will take place with documentation of several values of critical lab tests (catheter placement period).
Hepastem will be administered on 4 infusion days spread over an 8 week per
s metabolic condition will take place(infusion period).
-Transient percutaneous transhepatic catheter.
A transient percutaneous transhepatic catheter will be placed 3 times. Hepastem will be administe
s metabolic condition will take place(infusion period).
For both infusion procedures, schedule of admission and discharge of the child from the hospital /day hospital / clinical research facility will
Sponsors
HLB CELL
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.The patient is a pediatric patient<12 years prior to infusion. 2.The patient presents with one of the following UCDs(CPCS1D:carbamoylphosphate synthetase 1 deficiency, OTCD:ornitine transcarbamylase deficiency, ASSD:argininosuccinic acid synthetase deficiency, ASLD:arfininosuccinic acid lase deficiency, ARGD:arginase deficiency) 3.The patient has severe disease with inpaired protein tolerance defined as : chronic protein restricted diet and chronic treatment with at least one nitrogen scavenger. 4.The patient shows patency of the portal vein and its branches including mesenteric veins, with normal flow velocity as confirmed by Doppler Ultra Sono and accessibility of the portal vein and/ or affluants. 5.The patients (if capable of signing) and parents or legal representative have signed a written informed assent/consent form.
Exclusion criteria
Exclusion criteria: 1.The patient presents acute liver failure. 2.The patient presents clinical or radiological evidence of liver cirrhosis. 3.The patient presents or has a history of hepatic or extrahepatic malignancy. 4.The patient has a known clinically significant cardiac malformation. 5.The patient has a personal history of venous thrombosis, or has a clinically signifiant abnormal value of protein S, Protein C, antithrombin 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 LL before enrolling the patient in the study. 6.Patients currently receiving other unlicensed clinical trial drugs. 7.The patient underwent previous mature liver cell or stem cell transplantation or received an organ liver transplant or eceived Hepastem infusion. 8.The patient has a contraindication to methylprednisolone, tacrolimus. 9.The patient has a known hypersensitivity or allergy to heparin. 10.The patient has a known hypersensitivity or allergy to the antiviotics preventing post-operative infections that are prescribed according to institutional guidelines, and no alternative prophylaxis can be found. 11.The patient had or has a renal insufficiency treated by dialysis. 12.The patient requires valproate therapy. 13.The patient has a knon hyperwensitivity or allergy to contrast agents ( if applicable) that cannot be treated adequately. 14.The patient has a thrombosis of the portal vein or persisting impairment of anterograde portal blood flow. 15.The patient has a porto systemic shunt or fistula assessed by Doppler US or an Arantius channel or portal hypertension. 16.The site where the catheter in intended to be placed has previously suffered from venous thrombosis or vascular surgical procedures. 17.The patient has an ongoing infection or sufferd from an infection in the last 2 weeks(including active EBV infection at screening). The patient may be enrolled after resolution of the infection. 18.There in any significant condition or disbility that, in the Investigator's opinion, may interfere with the patient's optimal participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ureagenesis improvement at 6 month post first infusion day(Follow up visit3) : absolute 13C blood urea AUC(area under the curve)-120 min quantified with the 13C tracer method at follow up visits compared with baseline evaluations(measurements at baseline visit1, baseline visit2 and baseline visit3).;Safety : Clinical tatus(physical examination and vital signs);Safety : Morphology of the liver, bile ducts, and portal system;Safety : Laboratory tests;de novo detection of donor-specific circulationg anti-human leukocyte antigen(HLA) antibodies at mean fluorescence intensity(MFI)>1500, and/or other immune-related markers;Safety : Serios Adverse Events(SAEs) and clinically significant Adverse Events(AEs) related to Hepastem (infusion and follow-up), technical intervention, and concomitant treatments.;Safety : Portal vein hemodynamics | — |
Secondary
| Measure | Time frame |
|---|---|
| Ureagenesis improvement at month 3, month 9 and month 12 post first infusion day(Follow up visits1,5,7): absolute 13C blood urea AUC-120 min quantified with the 13C tracer method at these visits compared with baseline evaluations(measurements at BL visit1, BL visit2 and visit3);Cognitive skills considering evaluation during the baseline period at baseline visit 1(baseline visit1) and during follow-up period at 12month post-first infusion(follow up visit7);Chronic protein intake considering diet evaluations at study visits during baseline period and at scheduled study visits during the follow-up period.;Chronic nitrogen scavenger dose considering reported doses at scheduled study visits during baseline period and at scheduled study visits during the follow-up period.;Blood ammonia considering values measured at scheduled study visits during screening and baseline periods ant at scheduled study visits during the foloow-up period.;Growth parameters collected duribg retrospective period(fora max of 3 years prior to study inclusion) and measured at scehduled study visits.;Relevant blood amino acids considering values measured at scheduled study visits during the screening and baseline periods and at scehduled study visits during the follow-up period.;Metabolic docempensatios;Chronic single animo acid intake considering reported doses at study visits during gaseline period and at study visits during the follow-up period.;Behavior and health-related Quality of Life indicators considering evaluations during baseline visit1, during foloow-up period at 4.5m, 7.5m and 12m post-first fusion (FU visits2,4,7) | — |
Countries
Korea, Republic of
Contacts
Public ContactSanghoon Lee
Samsung Medical Center
Outcome results
None listed