Hyperoxalaemia in patients with End Stage Kidney Disease.
Conditions
Interventions
Trade Name: Oxlumo (Lumasiran)
Product Name: Oxlumo
Product Code: EMEA/H/C/005040
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Lumasiran
Other descriptive name: Lumasiran sodium
Co
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Both male and female patients • Aged between =18 and =80 years old • Women of child-bearing age to consent to either abstinence or the use of contraception during the study period • Patients must have capacity to give written, informed consent to participate in the study prior to commencing the study. They must be fully aware of the aims, nature, planned interventions and potential risks of participating in the study • Established and stable on haemodialysis for at least 2 months • Thrice weekly haemodialysis • In possession of permanent dialysis access – either arterio-venous fistula (AVF) or graft (AVG) or permanent dialysis catheter/tunnelled haemodialysis line (THL) • Any cause of ESKD except previously diagnosed primary hyperoxaluria. • Baseline serum oxalate level of >20 µmol/L • No recent (within last 2 months) significant changes to regular medications or diet Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: • Age less than 18 or over 80 years old • Known diagnosis of PH1, 2 or 3; or a pathological mutation documented to cause primary hyperoxaluria • Established on haemodialysis for less than 3 months or on peritoneal dialysis or combined haemodialysis and peritoneal dialysis • Temporary or poorly functioning haemodialysis access • Pregnancy, planning pregnancy or currently breast feeding • Co-morbidity of an enteric disorder such as Inflammatory Bowel Disease (IBD), short gut syndrome, or a malabsorptive disorder. • Decompensated Liver failure • Intercurrent active infection and/or antibiotic treatment • Currently on Vitamin C treatment with a daily dose of more than 250mg • Terminal illness and/or life expectancy of less than 1 year • Currently relapsed or uncontrolled and symptomatic psychiatric disorder preventing compliance with the study • Patients who could be coerced due to dependency on the sponsor, the investigator or the trial sites • Deranged LFTs: If alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is more than twice the upper limit of normal, or if the total bilirubin is above 1.5x the upper limit of normal. If the patient is diagnosed with Gilbert’s syndrome then a total bilirubin up to twice the upper limit of normal is acceptable • Deranged clotting: Patients with an International normalised ratio (INR) of more than 2.0 will be excluded unless they are oral therapeutic anticoagulants in which case only an INR >3.5 will be unacceptable. • A history of multiple medical drug allergies or a history of allergy to an oligonucleotide or GalNAc • Currently taking any other investigational agent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess if this medication can successfully lower plasma oxalate levels in patients with End Stage Kidney Disease on haemodialysis. ;Secondary Objective: To assess: - safety and tolerability of this medication in this population - exploratory biomarkers for safety and cardiovascular health - any change in echocardiogram findings at the start and end of the trial;Primary end point(s): Primary Endpoint: The primary endpoint is the percentage/relative change in pre-dialysis plasma oxalate levels from baseline to month 6, using an average of measurements from month 3 through month 6. The treatment group will be compared with the placebo group.;Timepoint(s) of evaluation of this end point: Monthly for the 6 months after administration of the first dose of the IMP/placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Objectives/Endpoints: The secondary objectives include an assessment of safety and tolerability. The endpoints are: - Absolute change in pre-dialysis plasma oxalate levels from baseline to month 6, comparing the treatment group with the placebo group. - Tolerability will be assessed using an adapted FACIT Instrument validated questionnaire (severity of side effects rated on scale between 0 and 4). Again the answers of the two study arms will be compared. Additionally we will assess the following exploratory outcomes: - Overall mortality rate from day 1 until the end of the trial compared between the two groups. - Cardiovascular morbidity event rate from month 0 until the end of the trial compared between the two groups. - Changes in following exploratory biomarkers: full blood count, liver function tests including albumin, urea and electrolytes, HCO3-, inflammatory markers (C-Reactive Protein, CK, LDH, white blood cell count), bone profile, (calcium/phosphate), Troponin and NT-pro-BNP. Laboratory shift tables for these parameters will be produced on a monthly basis for both placebo and treatment groups from month 0 until month 6. This will allow comparison between the two groups and help identify if there are any potentially harmful trends. - Change in transthoracic echocardiogram findings between baseline and month 6. Speckle echocardiogram techniques will be used to primarily assess left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), both of these parameters are recorded as a percentage. An abnormal GLS is defined as <15%. We will report the percentage change in LVEF and/or GLS for both groups. A baseline abnormal LVEF is defined as <55%, and an abnormal GLS as <15%. We will record whether patients have an improvement of =5% in LVEF and/or an improvement on =2% in GLS. ;Timepoint(s) of evaluation of this end point: - Exploratory blood biomarkers will be taken every month prior to the dose of | — |
Countries
Germany
Contacts
Public ContactGerlineke Hawkins-van der Cingel
Charité Universitätsmedizin Berlin
Outcome results
None listed