The following is a summary of “Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial,” published in the February 2023 issue of the Kidney Diseases by Michael et al.
Patients with primary hyperoxaluria type 1 (PH1) with mild to moderately retained renal function benefit from lumasiran’s ability to lower oxalate levels in the urine and blood. Patients with PH1 and advanced kidney disease are being studied in the ILLUMINATE-C trial to assess the effectiveness, safety, pharmacokinetics, and pharmacodynamics of lumasiran. Third-stage, single-arm, open study. Patients with PH1 of any age, with or without systemic oxalosis, and an initial screening POx 20 mol/L participated in this multinational trial. Patients’ estimated glomerular filtration rates had to be 45 mL/min/1.73 m2 (if age 12 months) or their serum creatinine levels had to be elevated (if age 12 months).
Subcutaneous lumasiran injections every month for 3 months, then every month or every three months, depending on weight. The primary outcome measures are the percentage change in POx from baseline to month 6 (cohort A; not on hemodialysis at enrollment) and the percentage change in predialysis POx from baseline to month 6 (cohort B; on hemodialysis at enrolment). Secondary pharmacodynamic endpoints included percentage and absolute changes in POx area under the curve between dialysis sessions (cohort B only), spot urine oxalate-creatinine ratio changes, and 24-hour urinary oxalate changes after adjusting for body surface area. About 21 patients (43% women, 76% White) finished the primary analysis period of 6 months.
The average age of consent was 9, with a wide variation from 8 to 59. The primary outcome was a decrease in POx, and the least-squares means for cohort A (n = 6) and cohort B (n = 15) were 33.3% (95% CI, 15.2% to 81.8%) and 42.4% (95% CI, 34.2%-50.7%), respectively. All secondary pharmacodynamic endpoints also showed enhancements. Mild to moderate side effects were the most common. No one stopped taking their medication or dropped out of the trial. Injection-site reactions were the most commonly reported lumasiran-related adverse effects. However, they were all mild and short-lived. No placebos were used in this single-arm study. Patients with PH1 and severe kidney disease saw significant decreases in POx while taking lumasiran, proving the drug’s efficacy and safety.