Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles American Journal of Kidney Diseases Year : 2022

Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial

S. A. Bakkaloglu
  • Function : Author


RATIONALE & OBJECTIVE: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease. STUDY DESIGN: Phase 3, open-label, single-arm trial. SETTING & PARTICIPANTS: Multinational study; enrolled patients with PH1 of all ages, eGFR ≤45 mL/min/1.73m(2) (if age ≥12 months) or elevated serum creatinine (if age \textless12 months), and POx ≥20 μmol/L at screening, including patients with or without systemic oxalosis. EXPOSURE: Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing. OUTCOME: Primary endpoint: percent change in POx from baseline to Month 6 (Cohort A; not receiving hemodialysis at enrollment) and percent change in predialysis POx from baseline to Month 6 (Cohort B; receiving hemodialysis at enrollment). Pharmacodynamic secondary endpoints: percent change in POx area under the curve between dialysis sessions (Cohort B only); absolute change in POx; percent and absolute change in spot urinary oxalate:creatinine ratio, and 24-hour UOx corrected for body surface area. RESULTS: All patients (N=21; 43% female; 76% white) completed the 6-month primary analysis period. Median age at consent: 8 (range, 0-59) years. For the primary endpoint, least-squares mean reduction in POx in Cohort A (N=6) was 33.3% (95% CI, -15.2%, 81.8%) and in Cohort B (N=15) was 42.4% (95% CI, 34.2%, 50.7%). Improvements were also observed in all pharmacodynamic secondary endpoints. Most adverse events were mild or moderate. No patient discontinued treatment or withdrew from the study. The most commonly reported lumasiran-related adverse events were injection-site reactions, all mild and transient. LIMITATIONS: Single-arm study without placebo control. CONCLUSIONS: Lumasiran resulted in substantial reductions in POx with acceptable safety in patients with PH1 who have advanced kidney disease, supporting its efficacy and safety in this patient population.
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Dates and versions

inserm-03831070 , version 1 (26-10-2022)



M. Michael, J. W. Groothoff, H. Shasha-Lavsky, J. C. Lieske, Y. Frishberg, et al.. Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial. American Journal of Kidney Diseases, 2022, S0272-6386 (22), pp.00771-5. ⟨10.1053/j.ajkd.2022.05.012⟩. ⟨inserm-03831070⟩
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