- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04152200
A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1 (ILLUMINATE-C)
ILLUMINATE-C: A Single Arm Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1 (PH1)
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Expanded Access
Contacts and Locations
Study Locations
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Garran, Australia
- Clinical Trial Site
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Brussels, Belgium
- Clinical Trial Site
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Bron, France
- Clinical Trial Site
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Lyon, France
- Clinical Trial Site
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Haifa, Israel
- Clinical Trial Site
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Nahariya, Israel
- Clinical Trial Site
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Rome, Italy
- Clinical Trial Site
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Irbid, Jordan
- Clinical Trial Site
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Beirut, Lebanon
- Clinical Trial Site
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Amsterdam, Netherlands
- Clinical Trial Site
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Yenimahalle, Turkey
- Clinical Trial Site
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Dubai, United Arab Emirates
- Clinical Trial Site
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Minnesota
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Rochester, Minnesota, United States, 55902
- Clinical Trial Site
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Texas
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Houston, Texas, United States, 77030
- Clinical Trial Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Lumasiran
All patients will receive open-label lumasiran.
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Lumasiran will be administered by subcutaneous (SC) injection.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Cohort A: Percent Change in Plasma Oxalate From Baseline to Month 6
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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Cohort B: Percent Change in Pre-dialysis Plasma Oxalate From Baseline to Month 6
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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Absolute Change in Plasma Oxalate From Baseline to Month 6
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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Cohort A: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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Cohort A: Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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Cohort A: Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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Cohort A: Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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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
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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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
Time Frame: Baseline to Month 6
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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.
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Baseline to Month 6
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Maximum Plasma Concentration (Cmax) of Lumasiran
Time Frame: Day 1; Month 6
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Cmax is the highest concentration of lumasiran in the plasma after a dose is given.
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Day 1; Month 6
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Time to Maximum Plasma Concentration (Tmax) of Lumasiran
Time Frame: Day 1; Month 6
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Tmax is the time it takes for lumasiran to reach the maximum concentration (Cmax) after administration.
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Day 1; Month 6
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Elimination Half-life (t½β) of Lumasiran
Time Frame: Day 1; Month 6
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t½β is the time it takes for the concentration of the drug in the plasma to be reduced by 50%.
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Day 1; Month 6
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Area Under the Concentration-time Curve From 0 to 24 Hours [AUC(0-24)] for Lumasiran
Time Frame: Day 1; Month 6
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AUC(0-24) is the area under the plasma concentration-time curve over the last 24-h dosing interval.
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Day 1; Month 6
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Apparent Clearance (CL/F) of Lumasiran
Time Frame: Day 1; Month 6
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CL/F is the rate at which lumasiran is eliminated from the body.
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Day 1; Month 6
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Apparent Volume of Distribution (V/F) of Lumasiran
Time Frame: Day 1; Month 6
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V/F is the propensity of lumasiran to either remain in the plasma or redistribute to other tissues.
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Day 1; Month 6
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Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 60
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Absolute Change in Plasma Oxalate From Baseline to Month 60
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60
Time Frame: Baseline to Month 60
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Baseline to Month 60
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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
Time Frame: Baseline to Month 60
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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.
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Baseline to Month 60
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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
Time Frame: Baseline to Month 60
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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.
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Baseline to Month 60
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Percent Change in Plasma Oxalate From Baseline to End of Study
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Change in Nephrocalcinosis From Baseline to End of Study
Time Frame: Baseline to Month 60
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Nephrocalcinosis will be assessed by renal ultrasound.
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Baseline to Month 60
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Change in Frequency of Dialysis From Baseline to End of Study
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Change in Mode of Dialysis From Baseline to End of Study
Time Frame: Baseline to Month 60
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Modes of dialysis are defined as hemodialysis and peritoneal dialysis.
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Baseline to Month 60
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Change in Frequency of Renal Stone Events From Baseline to End of Study
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) From Baseline to End of Study
Time Frame: Baseline to Month 60
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Baseline to Month 60
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Change in Measures of Systemic Oxalosis From Baseline to End of Study
Time Frame: Baseline to Month 60
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Systemic oxalosis will be assessed in cardiac, skeletal, ophthalmologic, and dermatologic systems.
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Baseline to Month 60
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Medical Director, Alnylam Pharmaceuticals
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Kidney Diseases
- Urologic Diseases
- Genetic Diseases, Inborn
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Hyperoxaluria
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Hyperoxaluria, Primary
- Renal Agents
- Lumasiran
Other Study ID Numbers
- ALN-GO1-005
- 2019-001346-17 (EudraCT Number)
- 2023-503382-29-00 (Ctis)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU.
Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Primary Hyperoxaluria Type 1
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Dicerna Pharmaceuticals, Inc.CompletedKidney Diseases | Urologic Diseases | Genetic Disease | Primary Hyperoxaluria Type 1 (PH1) | Primary Hyperoxaluria Type 2 (PH2)Poland, United Kingdom, New Zealand, United States, Australia, Canada, France, Germany, Israel, Italy, Japan, Lebanon, Netherlands, Romania, Spain
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Alnylam PharmaceuticalsCompletedPrimary Hyperoxaluria Type 1 (PH1)France, United Kingdom, Netherlands, Israel, Germany
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Dicerna Pharmaceuticals, Inc., a Novo Nordisk companyEnrolling by invitationKidney Diseases | Urologic Diseases | Genetic Disease | Primary Hyperoxaluria Type 1 (PH1) | Primary Hyperoxaluria Type 2 (PH2) | Primary Hyperoxaluria Type 3 (PH3)United States, France, Germany, Japan, Lebanon, Spain, United Kingdom, Australia, Canada, Italy, Netherlands, Norway, Turkey
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Alnylam PharmaceuticalsCompletedPrimary Hyperoxaluria Type 1 (PH1)United States, France, United Kingdom, Switzerland, Netherlands, Israel, Germany, United Arab Emirates
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Dicerna Pharmaceuticals, Inc., a Novo Nordisk companyAvailablePrimary Hyperoxaluria Type 1 (PH1)
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Alnylam PharmaceuticalsActive, not recruitingPrimary Hyperoxaluria Type 1 (PH1) | Primary HyperoxaluriaUnited States, France, United Kingdom, Israel, Germany
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Dicerna Pharmaceuticals, Inc., a Novo Nordisk companyRecruitingPrimary Hyperoxaluria Type 3 | Primary Hyperoxaluria Type 2 | Primary Hyperoxaluria Type 1 | Primary HyperoxaluriaUnited States, Canada, Lebanon, Turkey, United Kingdom, Germany, Italy, Japan, Poland, Spain, United Arab Emirates
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Ann & Robert H Lurie Children's Hospital of ChicagoMayo Clinic; National Institute of Diabetes and Digestive and Kidney Diseases...CompletedPrimary Hyperoxaluria Type 1
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Dicerna Pharmaceuticals, Inc.TerminatedPrimary Hyperoxaluria Type 1Netherlands, Germany
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Hospices Civils de LyonCompletedIdiopathic Hypercalciuria | Primary Hyperoxaluria Type 1France
Clinical Trials on Lumasiran
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Charite University, Berlin, GermanyAlnylam PharmaceuticalsNot yet recruitingCardiovascular Disease | Cardiovascular Risk Factor | Haemodialysis | Chronic Kidney Disease Requiring Chronic Dialysis | Hyperoxalemia
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Alnylam PharmaceuticalsCompletedPrimary Hyperoxaluria | PH1 | RNAi Therapeutic | siRNA | AGTFrance, United Kingdom, Netherlands, Israel, Germany
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Alnylam PharmaceuticalsCompletedPrimary Hyperoxaluria Type 1 (PH1)United States, France, United Kingdom, Switzerland, Netherlands, Israel, Germany, United Arab Emirates
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Alnylam PharmaceuticalsCompletedPrimary Hyperoxaluria Type 1 (PH1)France, United Kingdom, Netherlands, Israel, Germany
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Alnylam PharmaceuticalsApproved for marketingPrimary HyperoxaluriaBelgium
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Alnylam PharmaceuticalsActive, not recruitingPrimary Hyperoxaluria Type 1 (PH1) | Primary HyperoxaluriaUnited States, France, United Kingdom, Israel, Germany
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Alnylam PharmaceuticalsTerminatedRecurrent Calcium Oxalate Kidney Stone Disease | Elevated Urinary Oxalate LevelsUnited States, Italy, Spain, Belgium, Switzerland, United Kingdom
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Genzyme, a Sanofi CompanyWithdrawnEndometrial CancerUnited States