Clinical Trial Results:
Human Liver Stem Cells (HLSCs) in patients suffering from liver-based inborn metabolic diseases causing life-threatening neonatal onset of hyperammonemic encephalopathy
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Summary
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EudraCT number |
2012-002120-33 |
Trial protocol |
IT |
Global end of trial date |
18 Jul 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Aug 2021
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First version publication date |
14 Aug 2021
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Other versions |
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Summary report(s) |
Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
HLSCS01-11
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
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Sponsor organisation address |
Corso Bramante 88, Torino, Italy, 10126
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Public contact |
Dr. Marco Spada, Centro Malattie Metaboliche/ Presidio Ospedaliero Regina Margherita, 39 0113135857, marco.spada@unito.it
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Scientific contact |
Dr. Marco Spada, Centro Malattie Metaboliche/ Presidio Ospedaliero Regina Margherita, 39 0113135857, marco.spada@unito.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Jul 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Jul 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Jul 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate hepatic and extra-hepatic complications after liver intraparenchymal HLSC injection in neonates suffering from inborn liver metabolic diseases causing life-threatening neonatal-onset of hyperammonemic encephalopathy
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Protection of trial subjects |
a total of two injections was administered, the first one as soon as the patient entered the study. The second admnistration had to be performed one week after the first, only in the absence of adverse events related to the first treatment. Each patient was regularly followed for clinical and laboratory aspects. Treatment was to be terminated in the following events: completion of 2 injections, unacceptable toxicity or withdrawal of consent.
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Background therapy |
Standard of care | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Oct 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy, Ethical reason, Regulatory reason, Scientific research | ||
Long term follow-up duration |
1 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 3
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Worldwide total number of subjects |
3
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EEA total number of subjects |
3
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
3
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
start date 10 Feb 2014; end date 18 Jan 2017 | |||||||||
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Pre-assignment
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Screening details |
Inclusion criteria: neonatal-onset hyperammonemic encephalopathy; formal biochemical diagnosis of one inborn metabolic disease (CPS1-, OTC-, ASS-, PCC-, MCM-, ASL-deficiency); formal evaluation for early OLT; be referred to OIRM, Centro Malattie Metaboliche, TO; Exclusion criteria: refusal of signing informed consent; uncontrolled coagulopathy. | |||||||||
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Period 1
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Period 1 title |
baseline
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Baseline to dose level 1 | |||||||||
Arm description |
baseline to subjects treated with 125,000 HLSC cells x gram of liver | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
HLSC
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intrahepatic use
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Dosage and administration details |
two doses of 125,000 HLSC cells x gram of liver administered at two weeks interval
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Arm title
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Baseline to dose level 2 | |||||||||
Arm description |
baseline to subjects treated with 250,000 HLSC cells x gram of liver | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
HLSC
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intrahepatic use
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Dosage and administration details |
two doses of 250,000 HLSC cells x gram of liver administered at two weeks interval
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Period 2
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Period 2 title |
treatment
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Is this the baseline period? |
No | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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dose level 1 | |||||||||
Arm description |
subjects treated with 125,000 HLSC cells x gram of liver | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
HLSC
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intrahepatic use
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Dosage and administration details |
two doses of 125,000 HLSC cells x gram of liver administered at two weeks interval
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Arm title
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dose level 2 | |||||||||
Arm description |
subjects treated with 250,000 HLSC cells x gram of liver | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
HLSC
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intrahepatic use
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Dosage and administration details |
two doses of 250,000 HLSC cells x gram of liver administered at two weeks interval
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Baseline characteristics reporting groups
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Reporting group title |
baseline
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Reporting group description |
A total of 3 subjects were screened and entered into the study. No significant differences between subjects of the two treatment groups were observed with respect to age, height and body weight. Subjects underwent a physical examination, instrumental examinations and measurement of vital signs at the screening visit. Moreover a series of pathological values were examined in order to perform the diagnosis for metabolic disease. Of note, at physical examination all patients presented hypotonia. All reported positive history for at least one abnormality at the Hematological system (anemia) and at the Neurological system (commonly hyperammonemia / hyperammonemic comas). All abnormalities were continuing at the time of the study entry, except for the neonatal hyperammonemia / hyperammonemic comas, which were resolved before the signature of the informed consent. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Baseline to dose level 1
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Reporting group description |
baseline to subjects treated with 125,000 HLSC cells x gram of liver | ||
Reporting group title |
Baseline to dose level 2
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Reporting group description |
baseline to subjects treated with 250,000 HLSC cells x gram of liver | ||
Reporting group title |
dose level 1
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Reporting group description |
subjects treated with 125,000 HLSC cells x gram of liver | ||
Reporting group title |
dose level 2
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Reporting group description |
subjects treated with 250,000 HLSC cells x gram of liver | ||
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End point title |
Hepatic complications [1] | |||||||||
End point description |
portal vein thrombosis, intrahepatic hematoma, injury of the hepatic artery, arterio-portal, portal-biliary and arterio-biliary fistula, acute hepatic cytolysis > 20 times normal, clinical and biochemical signs of liver failure (ascites, development of jaundice with conjugated bilirubin above 3 mg/dL, alterations in INR > 2.5), appearance of cancer-like liver nodular lesions
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End point type |
Primary
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End point timeframe |
from the administration of the first dose (V1) to 4 weeks after the administration of the second dose (V4).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The total study population was 3 subjects. Descriptive statistics (e.g., mean, standard deviation, minimum, maximum for continuous data; frequency tables for categorical data) are provided per dose level and overall. Summary statistics were provided per dose level and overall. Summary statistics: quantitative parameters were summarized using descriptive statistics: N, Mean, Median, STD,Minimum, Maximum; qualitative parameters were summarized using frequency tables: N and percentage (%). |
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Attachments |
Untitled (Filename: Overall summary of Adverse Events.pdf) Untitled (Filename: Summary of Adverse Events, by patient and overall.pdf) Untitled (Filename: Category of Adverse Events, by patient and overall.pdf) |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Extra-hepatic complications [2] | |||||||||
End point description |
pulmonary embolism, significant extra-hepatic (abdominal and/or chest) haemorrhage (requiring blood transfusion and / or specific treatment), documented sepsis with bacteremia, adverse reactions to sedative drugs administered for interventional radiological procedure
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End point type |
Primary
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End point timeframe |
from the administration of the first dose (V1) to 4 weeks after the administration of the second dose (V4).
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The total study population was 3 subjects. Descriptive statistics (e.g., mean, standard deviation, minimum, maximum for continuous data; frequency tables for categorical data) are provided per dose level and overall. Summary statistics were provided per dose level and overall. Summary statistics: quantitative parameters were summarized using descriptive statistics: N, Mean, Median, STD,Minimum, Maximum; qualitative parameters were summarized using frequency tables: N and percentage (%). |
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Attachments |
Overall summary of Adverse Events Summary of Adverse Events, by patient and overall Category of Adverse Events, by patient and overall |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
adverse events assessment started at baseline (signature of Informed Consent) and ended at the last visit (V4), 4 weeks after the administration of last dose.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
dose level 1
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Reporting group description |
subjects with two doses of 125,000 HLSC cells x gram of liver, administered at 2 weeks interval | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
dose level 2
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Reporting group description |
subjects with two doses of 250,000 HLSC cells x gram of liver, administered at 2 weeks interval | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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26 Sep 2014 |
n. 1 : to include into the study patients affected by Deficiency of argininosuccinate lyase (ASL) (protocol Version 1.2 26 aug 2014) |
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08 Jun 2016 |
n. 2: to extend product expiration date to 36 months (IMPD Quality Report HLSCs_Drug substance and drug product”, Vers. Final 1.1_17.02.16) |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/31792768 |
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