Hereditary Tyrosinemia, Type I
Conditions
Keywords
rare diseases, fumarylacetoacetate hydrolase (FAH) deficiency, liver failure, drug treatment, nitisinone, observational research, phase IV, China, pediatric patient
Brief summary
This is a prospective, non-interventional, non-comparative, multicenter study to collect data on HT-1 patients in China treated with Nitisinone in a routine clinical setting. No tests or examinations are mandated in the study.
Detailed description
This is a prospective, non-interventional, non-comparative, multicenter study to collect data on HT-1 patients in China treated with Nitisinone in a routine clinical setting. No tests or examinations are mandated in the study, though the expectation is that most of the tests and examinations listed in the protocol will be performed in the context of routine clinical care and relevant data will be captured. At enrollment, data on patient treatment, medical and surgical history together with other patient characteristics will be captured.Patients enrolled in the study will be followed for at least 1 year and for a maximum of 3.5 years. The study aims to enroll at least 15 HT-1 patients aged 0-18 years. If adult patients are enrolled the study population will be larger as all eligible patients will be invited to participate. However, the enrollment will close when the target of 15 patients aged 0-18 years has been reached.
Interventions
DRUGNitisinone
According to prescription
Sponsors
Swedish Orphan Biovitrum
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Patients with a confirmed diagnosis of HT-1 treated with, or at enrollment prescribed, Nitisinone treatment (product manufactured by Sobi) in a routine clinical care setting. The decision to initiate treatment shall be made by the treating physician independently from the decision to include the patient in the study. 2. Signed and dated informed consent provided by the patient, or the patient's legally authorized representative(s) for patients under the legal age, should be obtained before any study-related activities are undertaken. Assent should be obtained from pediatric patients according to local regulations
Exclusion criteria
1\. Enrollment in a concurrent clinical interventional study, or intake of an Investigational Medicinal Product (IMP), within three months prior to inclusion in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of hepatic, renal or hematological adverse events (AEs) or death | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Number and percent of patients with occurrence and number of occurrences per 100 patient years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of liver transplantation | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Number and percent of patients with occurrence and number of occurrences per 100 patient years. |
| Occurrence of hepatic malignancy | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Number and percent of patients with occurrence and number of occurrences per 100 patient years. |
| Occurrence of other (non-hepatic) malignancies | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Number and percent of patients with occurrence and number of occurrences per 100 patient years. |
| Occurrence of ophthalmic events | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Number and percent of patients with occurrence and number of occurrences per 100 patient years. |
| Occurrence of neurological events | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Number and percent of patients with occurrence and number of occurrences per 100 patient years. |
| Occurrence of cognitive, developmental function AEs | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Cognitive, developmental function AEs will be recorded in the eCRF. |
| Occurrence of any reportable AEs | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Number and percent of patients with occurrence and number of occurrences per 100 patient years. Reportable AEs are defined as: * All Serious Adverse Events (SAEs) irrespective of causality with Nitisinone * Non-serious Adverse Events (AEs) assessed as causally related to treatment with Nitisinone * All Adverse Events leading to subject discontinuation from the study |
| Treatment and diet compliance | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Rated from 1 (very good) to 4 (very poor) and unknown. Number and percent of patients in each group. |
| Extent of exposure | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Extent of exposure as measured by: * Prescribed daily dose of Nitisinone * Changes in prescribed doses of Nitisinone |
| Extent of Exposure | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Extent of exposure as measured by: * Nitisinone trough concentrations in dried blood spot * Nitisinone trough concentrations in serum or plasma (depending on method) |
| Occurrence of death | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Number and percent of patients with occurrence and number of occurrences per 100 patient years. |
| Laboratory investigations - Blood Coagulation (2) | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Mean, median, standard deviation, minimum, and maximum time for ad-hoc specified age groups will be calculated for: • Partial thromboplastin time (milliseconds) |
| Laboratory investigations - Blood Coagulation (3) | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Mean, median, standard deviation, minimum, and maximum time for ad-hoc specified age groups will be calculated for: • Activated partial thromboplastin time (seconds per ration) |
| Laboratory investigations - Blood Chemistry (1) | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Mean, median, standard deviation, minimum, and maximum concentration for ad-hoc specified age groups will be calculated for blood concentrations of: * Tyrosine (µmol/L) * Phenylalanine (µmol/L) * Succinylacetone (µmol/L) * Creatinine (µmol/L) * Aspartate transaminase (µmol/L) * Serum bilirubin (µmol/L) |
| Laboratory investigations - Blood Chemistry (2) | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Mean, median, standard deviation, minimum, and maximum concentration for ad-hoc specified age groups will be calculated for blood concentrations of: • Alpha-fetoprotein (ng/mL) |
| Laboratory investigations - Blood Chemistry (3) | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Mean, median, standard deviation, minimum, and maximum concentration for ad-hoc specified age groups will be calculated for blood concentrations of: * Alanine transaminase (international units per liter) * Alkaline phosphatase (international units per liter) * Gamma-glutamyl transferase (international units per liter) |
| Laboratory investigations - Blood Chemistry (4) | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Mean, median, standard deviation, minimum, and maximum concentration for ad-hoc specified age groups will be calculated for blood concentrations of: • Albumin (g/L) |
| Overall clinical condition as assessed by the investigator | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Overall clinical condition will be assessed by the investigator on a 4-point scale; normal, mildly ill, moderately ill, markedly ill. Number and percent of patients in each group. |
| Ophthalmic status as assessed by the investigator | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | As assessed by the investigator (yes, normal, no, not normal, and unknown). Number and percent of patients in each group. |
| Neurocognitive/developmental status as assessed by the investigator | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | As assessed by the investigator (yes, normal, no, not normal, and unknown). Number and percent of patients in each group. |
| Laboratory investigations - Blood Coagulation (1) | Data will be collected for all routine visits completed during the study period which is at least 12 months but no more than 3.5 years. | Mean, median, standard deviation, minimum, and maximum time for ad-hoc specified age groups will be calculated for: • Prothrombin time (International Normalized Ratio) |
Countries
China
Outcome results
None listed