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

Hereditary Tyrosinemia, Type I Clinical Trial

Official title:

A Prospective, Non-interventional, Post-Marketing Study to Describe Outcome of Nitisinone Treatment in Hereditary Tyrosinemia Type 1 (HT-1) Patients in Routine Clinical Care in China

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06227429
• Other study ID #: Sobi.NTBC-008
• Status: Recruiting
• Start date: December 14, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: February 2024
• Source: Swedish Orphan Biovitrum
• Contact: Catrine Berlin, MSc
• Phone: +46(0)86972000
• Email: Catrine.Berlin[@]sobi.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hereditary Tyrosinemia, Type I
• Tyrosinemias

Intervention

Drug:
• Nitisinone
According to prescription

Locations

Country	Name	City	State
China	Swedish Orphan Biovitrum Research Site	Beijing
China	Swedish Orphan Biovitrum Research Site	Chongqing
China	Swedish Orphan Biovitrum Research Site	Hefei
China	Swedish Orphan Biovitrum Research Site	Wuhan

Sponsors (1)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of hepatic, renal or hematological adverse events (AEs) or death	Number and percent of patients with occurrence and number of occurrences per 100 patient years.	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.
Secondary	Occurrence of death	Number and percent of patients with occurrence and number of occurrences per 100 patient years.	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.
Secondary	Occurrence of liver transplantation	Number and percent of patients with occurrence and number of occurrences per 100 patient years.	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.
Secondary	Occurrence of hepatic malignancy	Number and percent of patients with occurrence and number of occurrences per 100 patient years.	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.
Secondary	Occurrence of other (non-hepatic) malignancies	Number and percent of patients with occurrence and number of occurrences per 100 patient years.	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.
Secondary	Occurrence of ophthalmic events	Number and percent of patients with occurrence and number of occurrences per 100 patient years.	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.
Secondary	Occurrence of neurological events	Number and percent of patients with occurrence and number of occurrences per 100 patient years.	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.
Secondary	Occurrence of cognitive, developmental function AEs	Cognitive, developmental function AEs will be recorded in the eCRF.	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.
Secondary	Occurrence of any reportable AEs	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	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.
Secondary	Treatment and diet compliance	Rated from 1 ("very good") to 4 ("very poor") and "unknown". Number and percent of patients in each group.	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.
Secondary	Extent of exposure	Extent of exposure as measured by: Prescribed daily dose of Nitisinone; Changes in prescribed doses of Nitisinone	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.
Secondary	Extent of Exposure	Extent of exposure as measured by: Nitisinone trough concentrations in dried blood spot; Nitisinone trough concentrations in serum or plasma (depending on method)	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.
Secondary	Laboratory investigations - Blood Coagulation (1)	Mean, median, standard deviation, minimum, and maximum time for ad-hoc specified age groups will be calculated for: • Prothrombin time (International Normalized Ratio)	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.
Secondary	Laboratory investigations - Blood Coagulation (2)	Mean, median, standard deviation, minimum, and maximum time for ad-hoc specified age groups will be calculated for: • Partial thromboplastin time (milliseconds)	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.
Secondary	Laboratory investigations - Blood Coagulation (3)	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)	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.
Secondary	Laboratory investigations - Blood Chemistry (1)	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)	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.
Secondary	Laboratory investigations - Blood Chemistry (2)	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)	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.
Secondary	Laboratory investigations - Blood Chemistry (3)	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)	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.
Secondary	Laboratory investigations - Blood Chemistry (4)	Mean, median, standard deviation, minimum, and maximum concentration for ad-hoc specified age groups will be calculated for blood concentrations of: • Albumin (g/L)	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.
Secondary	Overall clinical condition as assessed by the investigator	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.	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.
Secondary	Ophthalmic status as assessed by the investigator	As assessed by the investigator ("yes, normal", "no, not normal", and "unknown"). Number and percent of patients in each group.	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.
Secondary	Neurocognitive/developmental status as assessed by the investigator	As assessed by the investigator ("yes, normal", "no, not normal", and "unknown"). Number and percent of patients in each group.	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.