Lumasiran in Hyperoxalaemic Patients on Haemodialysis

NCT06225544 | Recruiting Phase 2

• 2 other identifiers: 200185102022-002681-32
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. This study will investigate 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 all the participants will 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.

Conditions

Haemodialysis; Chronic Kidney Disease Requiring Chronic Dialysis; Cardiovascular Disease; Cardiovascular Risk Factor; Hyperoxalemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Absolute change in pre-dialysis mean plasma

  Baseline to month 3-6,

• Side effects (tolerability)

  Monthly - month 0-6

Study Arms (2)

Lumasiran, treatment arm

EXPERIMENTAL

Treatment arm with Lumasiran

Drug: Lumasiran

Placebo

PLACEBO COMPARATOR

Placebo injection with 0.9% sodium chloride

Drug: 0.9% Sodium Chloride (placebo)

Interventions

Lumasiran DRUG

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

Lumasiran, treatment arm

0.9% Sodium Chloride (placebo) DRUG

Placebo, subcutaneous injection, given as three monthly loading doses followed by one further maintenance dose.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Alnylam Pharmaceuticals: collaborator

Study Sites (1)

Charite Universtiätsmedizin

Berlin, Germany

RECRUITING

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

lumasiran; Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Felix Knauf, MD

  Charite Universitätsmedizin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gerlineke MC Hawkins-van der Cingel, MBBS

CONTACT

+ 49 030 450 530067; gerlineke.hawkins-van-der-cingel@charite.de

Felix Knauf, MD

CONTACT

+ 49 030 450 530066; felix.knauf@charite.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy PI

Model Details: This is a randomised controlled trial with parallel arms of placebo versus study drug (lumasiran). With a 1:1 ratio between the two groups.

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: January 26, 2024
• Study Start: April 14, 2024
• Primary Completion: January 30, 2025
• Study Completion: March 1, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)