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

Primary Hyperoxaluria Type 1 (PH1) Clinical Trial

— ILLUMINATE-A  

Official title:

ILLUMINATE-A: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study With an Extended Dosing Period to Evaluate the Efficacy and Safety of Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03681184
• Other study ID #: ALN-GO1-003
• Secondary ID: 2018-001981-40
• Status: Completed
• Phase: Phase 3
• Start date: November 27, 2018
• Est. completion date: January 12, 2024

Study information

• Verified date: February 2024
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: January 12, 2024
• Est. primary completion date: November 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperoxaluria, Primary
• Primary Hyperoxaluria Type 1 (PH1)

Intervention

Drug:
• Placebo
Placebo by SC injection
• Lumasiran
Lumasiran by SC injection

Locations

Country	Name	City	State
France	Clinical Trial Site	Lyon
France	Clinical Trial Site	Paris
Germany	Clinical Trial Site	Bonn
Israel	Clinical Trial Site	Haifa
Israel	Clinical Trial Site	Jerusalem
Israel	Clinical Trial Site	Nahariya
Netherlands	Clinical Trial Site	Amsterdam
Switzerland	Clinical Trial Site	Bern
United Arab Emirates	Clinical Trial Site	Dubai
United Kingdom	Clinical Trial Site	Birmingham
United Kingdom	Clinical Trial Site	London
United Kingdom	Clinical Trial Site	London
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Jacksonville	Florida
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Rochester	Minnesota
United States	Clinical Trial Site	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel,  Netherlands,  Switzerland,  United Arab Emirates,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of Renal Stone Events	A renal stone event is defined as a patient-reported event that includes =1 of the following: visit to healthcare provider because of a renal stone; medication for renal colic; stone passage; macroscopic hematuria due to a renal stone. Lower rates indicate a favorable outcome.	12-Month Period prior to Informed Consent, 6-Month DB Period
Other	Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound	Renal ultrasound data were used to grade medullary nephrocalcinosis findings (range: 0 to 3), where a higher grade indicates greater severity. Improving=if both sides improve, or one side improves and the other side has no change; No change=if both sides have no change; Worsening=if both sides worsen, or one side worsens and the other side has no change; Indeterminate=if one side improves and the other side worsens.	Baseline, Month 6
Primary	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.	Baseline to Month 6
Secondary	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.	Baseline to Month 6
Secondary	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.	Baseline to Month 6
Secondary	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.	Month 6
Secondary	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.	Month 6
Secondary	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.	Baseline to Month 6
Secondary	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.	Baseline to Month 6
Secondary	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 <18 years of age at screening. Change from baseline to Month 6 is reported.	Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6
Secondary	Absolute Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period		Up to 60 months
Secondary	Percentage Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period		Up to 60 months
Secondary	Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During the Extension Period		Up to 60 months
Secondary	Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline Over Time During the Extension Period		Up to 60 months
Secondary	Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time During the Extension Period		Up to 60 months