A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1

Alnylam Pharmaceuticals39 enrolled

Overview

The purpose of this study is to evaluate the efficacy and safety of lumasiran in children and adults with primary hyperoxaluria type 1 (PH1).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Primary Hyperoxaluria Type 1 (PH1)

Interventions

PlaceboDRUG

Placebo by SC injection

LumasiranDRUG

Lumasiran by SC injection

Eligibility

Sex: ALLMin age: 6 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Willing to provide written informed consent or assent and to comply with study requirements * Confirmation of PH1 disease * Meet the 24 hour urine oxalate excretion requirements * If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days Exclusion Criteria: * Clinically significant health concerns (with the exception of PH1) or clinical evidence of extrarenal systemic oxalosis * Clinically significant abnormal laboratory results * Known active or evidence of HIV or hepatitis B or C infection * An estimated GFR of \< 30 mL/min/1.73m\^2 at screening * Received an investigational agent within 30 days or 5 half-lives before the first dose of study drug or are in follow-up of another clinical study * History of kidney or liver transplant * Known history of multiple drug allergies or allergic reaction to an oligonucleotide or GalNAc * History of intolerance to subcutaneous injection * Women who are pregnant, planning a pregnancy, or breast-feeding or those of child bearing potential and not willing to use contraception * History of alcohol abuse within the last 12 months, or unable or unwilling to limit alcohol consumption throughout the study

Locations (17)

Clinical Trial Site

San Diego, California, United States

Clinical Trial Site

Jacksonville, Florida, United States

Clinical Trial Site

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6

Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.

Time frame: Baseline to Month 6

Secondary Outcomes

Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6

Absolute change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average absolute change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.

Time frame: Baseline to Month 6

Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6

Percent change in 24-hour urinary oxalate:creatine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.

Time frame: Baseline to Month 6

Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6

The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m\^2 for 24-hour urinary oxalate excretion corrected for BSA.

Time frame: Month 6

Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6

The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m\^2 for 24-hour urinary oxalate excretion corrected for BSA.

Time frame: Month 6

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Clinical Trial Site

New York, New York, United States

Clinical Trial Site

Cleveland, Ohio, United States

Clinical Trial Site

Lyon, France

Clinical Trial Site

Paris, France

Clinical Trial Site

Bonn, Germany

Clinical Trial Site

Haifa, Israel

Clinical Trial Site

Jerusalem, Israel

...and 7 more locations

Percentage Change in Plasma Oxalate From Baseline to Month 6

Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.

Time frame: Baseline to Month 6

Absolute Change in Plasma Oxalate From Baseline to Month 6

Absolute change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome.

Time frame: Baseline to Month 6

Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6

eGFR is calculated from serum creatinine based on the Modification of Diet in Renal Disease formula for patients ≥18 years of age and the Schwartz Bedside Formula for patients \>1 year to \<18 years of age at screening. Change from baseline to Month 6 is reported.

Time frame: Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6

Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for BSA From Baseline in the Extension Period

Absolute change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average absolute change from baseline in the extension periods. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.

Time frame: From Baseline to Month 54 and Month 60

Percentage Change in 24-hour Urinary Oxalate Excretion Corrected by BSA From Baseline in the Extension Period

Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline in the extension periods. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.

Time frame: From Baseline to Month 54 and Month 60

Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During Lumasiran Treatment

The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m\^2 for 24-hour urinary oxalate excretion corrected for BSA.

Time frame: Up to Month 60

Absolute Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline in the Extension Period

Absolute change in 24-hour urinary oxalate:creatinine ratio was estimated by an average absolute change from baseline to the end of the OLE period at Month 54 and Month 60. A negative change from Baseline indicates a favorable outcome.

Time frame: From Baseline to Month 54 and Month 60

Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline in the Extension Period

Time frame: From Baseline to Month 54 and Month 60

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical investigational participant administered a medicinal product \& which does not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization/prolongation of existing hospitalization, results in persistent/significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event that may not be immediately life-threatening/result in death/hospitalization but may jeopardize the participant \& may require intervention to prevent one of the other outcomes listed above. All Lumasiran Treated Set: All participants who received any amount of lumasiran including participants who took lumasiran during 6-month double-blinded period \& participants who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period.

Time frame: DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60).