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A Non-interventional, Post-Marketing Study to Describe Outcome of Nitisinone Treatment in HT-1 Patients

Recruiting
Conditions
Hereditary Tyrosinemia, Type I
Interventions
Registration Number
NCT06227429
Lead Sponsor
Swedish Orphan Biovitrum
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
15
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Full Analysis Set (FAS)NitisinoneThe Full Analysis Set (FAS) will include all patients with a confirmed HT-1 diagnosis on Nitisinone treatment in routine clinical care, who provide signed informed consent. Patients must be either on treatment with Nitisinone at study entry or they must have been prescribed Nitisinone at enrollment. No specific exclusion criteria from the analysis set will be applied. The FAS will be used for all analyses.
Primary Outcome Measures
NameTimeMethod
Occurrence of hepatic, renal or hematological adverse events (AEs) or deathData 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 Outcome Measures
NameTimeMethod
Occurrence of deathData 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 malignancyData 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) malignanciesData 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 AEsData 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.

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 (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)

Occurrence of liver transplantationData 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 any reportable AEsData 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

Extent of ExposureData 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)

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)

Neurocognitive/developmental status as assessed by the investigatorData 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.

Occurrence of ophthalmic eventsData 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.

Extent of exposureData 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

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)

Occurrence of neurological eventsData 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.

Treatment and diet complianceData 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.

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)

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)

Overall clinical condition as assessed by the investigatorData 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 investigatorData 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.

Trial Locations

Locations (1)

Swedish Orphan Biovitrum Research Site

🇨🇳

Wuhan, China

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