Lumasiran in Hyperoxalaemic Patients on Haemodialysis

Cardiovascular Disease Clinical Trial

— LHOxH  

Official title:

Lumasiran in Hyperoxalaemic Patients on Haemodialysis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06225544
• Other study ID #: 20018510
• Secondary ID: 2022-002681-32
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 1, 2024
• Est. completion date: January 15, 2025

Study information

• Verified date: January 2024
• Source: Charite University, Berlin, Germany
• Contact: Gerlineke MC Hawkins-van der Cingel, MBBS
• Phone: + 49 030 450 530067
• Email: gerlineke.hawkins-van-der-cingel[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will look at how well a drug that reduced the amount of oxalate in the body works in patients that have kidney disease and need dialysis treatment. People with kidney disease often have higher levels of oxalate in the blood. People with kidney disease are also at higher risk of having heart attacks, heart disease and strokes (these are called cardiovascular diseases). It is thought that high oxalate levels may increase the risk of these diseases. So we would like to study if this medicine can lower the amount of oxalate in the blood of dialysis patients and see if there is any change in the health of their heart. This medicine is already used for people who have high oxalate levels because of a genetic cause and has been used safely for patients on dialysis.

The study will put the participants randomly into either the group getting the study medicine or the group getting a placebo (this will be a solution of saline water). Neither participants not the doctors will know whether the drug or placebo is given until after the end of the study.

At the start of the study we will ask all the participants to have an echocardiogram (an ultrasound of the heart) and again 6 months later at the end of the study. We will also take blood tests once a month when the participants come for dialysis.

Description:

This is an investigator-initiated, double-blind, phase II two-centre medications study with an intervention and placebo arm.

The principal objective of this study is to establish if the administration of lumasiran versus placebo can effectively lower pre-dialysis oxalate levels in hyperoxalaemic haemodialysis patients with any cause of ESKD (end stage kidney disease) except known primary hyperoxaluria.

Our hypothesis is that compared to placebo, the administration of lumasiran (the study drug) will reduce serum oxalate levels at 3-6 months post first dose in hyperoxalaemic haemodialysis patients.

This study will evaluate the use of lumasiran in haemodialysis patients. Lumasiran will be dosed as per the SmPC published by the European Medicines Agency. Monthly pre-dialysis plasma oxalate measurements will be taken to assess the effect of lumasiran on lowering the oxalate levels versus a placebo. Thus far studies have shown lumasiran to be well tolerated. We will evaluate tolerability in this patient cohort and monitor inflammatory and cardiovascular biomarkers in addition to cardiac imaging with echocardiograms.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: January 15, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Male or female patients Aged between 18 and 80 years old at the start of the study. Women of child-bearing potential 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. This consent must be obtained by the time of participant inclusion.

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) ESKD not caused by previously diagnosed primary hyperoxaluria. Mean baseline serum oxalate level of =20 µmol/L No recent (within last 2 months) significant changes to regular medications or diet

Exclusion Criteria:

Known diagnosis of PH1, 2 or 3; or a pathological mutation documented to cause primary hyperoxaluria.

Established on haemodialysis for less than 2 months. On peritoneal dialysis Combined haemodialysis and peritoneal dialysis Temporary or poorly functioning haemodialysis access (see Section 5c for further definition) 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.

Participants institutionalised by court or government order. Patients who could be coerced due to dependency on the sponsor, the investigator, the trial sites or test centres.

Deranged liver function tests: 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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Cardiovascular Risk Factor
• Chronic Kidney Disease Requiring Chronic Dialysis
• Haemodialysis
• Hyperoxalemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Lumasiran
Subcutaneous injection, given as three monthly loading doses followed by one further maintenance dose.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Alnylam Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pre-dialysis Plasma Oxalate concentration	The primary endpoint is the percentage change in pre-dialysis plasma oxalate levels in non-primary hyperoxaluria patients with raised plasma oxalate levels who are receiving maintenance haemodialysis.	It will be measured at baseline and month 1-6 (weeks 4, 8, 12, 16, 20 and 24).
Secondary	Absolute change in pre-dialysis mean plasma	Absolute change in pre-dialysis mean plasma oxalate levels from baseline to month 3-6, comparing the treatment group with the placebo group.	Baseline to month 3-6,
Secondary	Side effects (tolerability)	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.	Monthly - month 0-6