A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1

Primary Hyperoxaluria Clinical Trial

— ILLUMINATE-C  

Official title:

ILLUMINATE-C: A Single Arm Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1 (PH1)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04152200
• Other study ID #: ALN-GO1-005
• Secondary ID: 2019-001346-1720
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 21, 2020
• Est. completion date: July 2025

Study information

• Verified date: April 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, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of lumasiran in patients with Advanced Primary Hyperoxaluria Type 1 (PH1).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: July 2025
• Est. primary completion date: May 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Has documented diagnosis of primary hyperoxaluria type 1 (PH1)
• Estimated glomerular filtration rate (eGFR) =45 mL/min/1.73 m^2 for patients =12 months of age (<12 months of age, must have serum creatinine considered elevated for age)
• Meets plasma oxalate level requirements
• If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days
• If on dialysis, may be on hemodialysis therapy only and must have been on a stable regimen for at least 4 weeks

Exclusion Criteria:

• Hemodialysis/peritoneal dialysis combination therapy or peritoneal dialysis alone
• Diagnosis of conditions other than PH1 contributing to renal insufficiency
• History of liver transplant
• History of kidney transplant and currently receiving immunosuppressants

Related Conditions & MeSH terms

• Hyperoxaluria, Primary
• Primary Hyperoxaluria
• Primary Hyperoxaluria Type 1

Intervention

Drug:
• Lumasiran
Lumasiran will be administered by subcutaneous (SC) injection.

Locations

Country	Name	City	State
Australia	Clinical Trial Site	Garran
Belgium	Clinical Trial Site	Brussels
France	Clinical Trial Site	Bron
France	Clinical Trial Site	Lyon
Israel	Clinical Trial Site	Haifa
Israel	Clinical Trial Site	Nahariya
Italy	Clinical Trial Site	Rome
Jordan	Clinical Trial Site	Irbid
Lebanon	Clinical Trial Site	Beirut
Netherlands	Clinical Trial Site	Amsterdam
Turkey	Clinical Trial Site	Yenimahalle
United Arab Emirates	Clinical Trial Site	Dubai
United States	Clinical Trial Site	Houston	Texas
United States	Clinical Trial Site	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Israel,  Italy,  Jordan,  Lebanon,  Netherlands,  Turkey,  United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort A: Percent 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. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran.	Baseline to Month 6
Primary	Cohort B: Percent Change in Pre-dialysis 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. For Cohort B, the baseline is defined as the mean of the last four pre-dialysis plasma oxalate samples collected prior to the first dose of lumasiran. In Cohort B, only pre-dialysis samples are utilized.	Baseline to Month 6
Secondary	Cohort B: Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 6	Percent change in plasma oxalate AUC(0-24) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Baseline was defined as the mean value of all valid AUC (µmol/L/24h) profiles being computed prior to the first dose of lumasiran.	Baseline to Month 6
Secondary	Absolute Change in Plasma Oxalate From Baseline to Month 6	Absolute change in plasma oxalate was estimated by an average absolute change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran; for Cohort B, the baseline was defined as the mean of the last 4 pre-dialysis plasma oxalate level values collected prior to the first dose of lumasiran. In Cohort B patients, the plasma oxalate baseline was similarly defined except that the values obtained from the plasma oxalate profile assessment visits only included the pre-dialysis sample collected per visit.	Baseline to Month 6
Secondary	Cohort A: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (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 is defined as the median of all valid 24-hr urine assessments collected prior to the first dose date/time of lumasiran without any non-protocol-related sample issues.	Baseline to Month 6
Secondary	Cohort A: 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 is defined as the mean of all assessments prior to the first dose date/time of lumasiran.	Baseline to Month 6
Secondary	Cohort A: Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6	Absolute change in spot urinary oxalate:creatinine ratio was estimated by an average absolute change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Baseline was defined as the mean of all assessments prior to the first dose date/time of lumasiran.	Baseline to Month 6
Secondary	Cohort A: Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6	Percent change in spot urinary oxalate:creatinine 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 was defined as the mean of all assessments prior to the first dose date/time of lumasiran.	Baseline to Month 6
Secondary	Change in Quality of Life As Assessed by Pediatric Quality of Life Inventory (PedsQL) Total Score From Baseline to Month 6 in Patients >=2 to 18 Years of Age at Time of Informed Consent	Peds-QL is a modular approach to measuring quality of life (QOL) in healthy children and adolescents and those with acute and chronic health conditions. The PedsQL Generic Core Scales contain 23 items designed to measure core domains of health (physical, emotional, and social functioning) and role (school functioning). Scores are summarized as Total Scale Score, Physical Health Summary Score, and Psychosocial Health Summary Score. The Total Scale Score will be reported for this study. The PedsQL will be completed by patients (or caregivers, as appropriate) who are =2 to <18 years of age at the time of consent. Total score range: 0 - 100, with higher scores indicating better health-related quality of life (HRQoL). Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.	Baseline to Month 6
Secondary	Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 6 in Patients =18 Years of Age at Time of Informed Consent	The KDQOL questionnaire is used to assess 3 core domains of kidney disease including: burden, symptoms/problems, and effects of kidney disease on daily life. The KDQOL subscales (Burden of Kidney Disease, Effect of Kidney Disease on Daily Life, and Symptoms and Problems of Kidney Disease), and the accompanying Short Form-12 (SF-12) Physical Component Summary and Mental Component Summary will be assessed for this study. These will be completed by patients who are =18 years of age at the time of consent. Score range (per domain): 0 - 100; higher scores indicate better HRQoL. Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.	Baseline to Month 6
Secondary	Maximum Plasma Concentration (Cmax) of Lumasiran	Cmax is the highest concentration of lumasiran in the plasma after a dose is given.	Day 1; Month 6
Secondary	Time to Maximum Plasma Concentration (Tmax) of Lumasiran	Tmax is the time it takes for lumasiran to reach the maximum concentration (Cmax) after administration.	Day 1; Month 6
Secondary	Elimination Half-life (t½ß) of Lumasiran	t½ß is the time it takes for the concentration of the drug in the plasma to be reduced by 50%.	Day 1; Month 6
Secondary	Area Under the Concentration-time Curve From 0 to 24 Hours [AUC(0-24)] for Lumasiran	AUC(0-24) is the area under the plasma concentration-time curve over the last 24-h dosing interval.	Day 1; Month 6
Secondary	Apparent Clearance (CL/F) of Lumasiran	CL/F is the rate at which lumasiran is eliminated from the body.	Day 1; Month 6
Secondary	Apparent Volume of Distribution (V/F) of Lumasiran	V/F is the propensity of lumasiran to either remain in the plasma or redistribute to other tissues.	Day 1; Month 6
Secondary	Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 60		Baseline to Month 60
Secondary	Absolute Change in Plasma Oxalate From Baseline to Month 60		Baseline to Month 60
Secondary	Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60		Baseline to Month 60
Secondary	Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60		Baseline to Month 60
Secondary	Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60		Baseline to Month 60
Secondary	Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60		Baseline to Month 60
Secondary	Change in Quality of Life As Assessed by Pediatric Quality of Life Inventory (PedsQL) Total Score From Baseline to Month 60 in Patients >=2 to 18 Years of Age at Time of Informed Consent	Peds-QL is a modular approach to measuring quality of life (QOL) in healthy children and adolescents and those with acute and chronic health conditions. The PedsQL Generic Core Scales contain 23 items designed to measure core domains of health (physical, emotional, and social functioning) and role (school functioning). Scores are summarized as Total Scale Score, Physical Health Summary Score, and Psychosocial Health Summary Score. The Total Scale Score will be reported for this study. The PedsQL will be completed by patients (or caregivers, as appropriate) who are =2 to <18 years of age at the time of consent. Total score range: 0 - 100, with higher scores indicating better health-related quality of life (HRQoL). Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.	Baseline to Month 60
Secondary	Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 60 in Patients =18 Years of Age at Time of Informed Consent	The KDQOL questionnaire is used to assess 3 core domains of kidney disease including: burden, symptoms/problems, and effects of kidney disease on daily life. The KDQOL subscales (Burden of Kidney Disease, Effect of Kidney Disease on Daily Life, and Symptoms and Problems of Kidney Disease), and the accompanying Short Form-12 (SF-12) Physical Component Summary and Mental Component Summary will be assessed for this study. These will be completed by patients who are =18 years of age at the time of consent. Score range (per domain): 0 - 100; higher scores indicate better HRQoL. Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.	Baseline to Month 60
Secondary	Percent Change in Plasma Oxalate From Baseline to End of Study		Baseline to Month 60
Secondary	Change in Nephrocalcinosis From Baseline to End of Study	Nephrocalcinosis will be assessed by renal ultrasound.	Baseline to Month 60
Secondary	Change in Frequency of Dialysis From Baseline to End of Study		Baseline to Month 60
Secondary	Change in Mode of Dialysis From Baseline to End of Study	Modes of dialysis are defined as hemodialysis and peritoneal dialysis.	Baseline to Month 60
Secondary	Change in Frequency of Renal Stone Events From Baseline to End of Study		Baseline to Month 60
Secondary	Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) From Baseline to End of Study		Baseline to Month 60
Secondary	Change in Measures of Systemic Oxalosis From Baseline to End of Study	Systemic oxalosis will be assessed in cardiac, skeletal, ophthalmologic, and dermatologic systems.	Baseline to Month 60