Primary Hyperoxaluria Type 1Phase 3ILLUMINATE-CNCT04152200
A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1
A Phase 3 study testing Lumasiran in people with Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria, run by Alnylam Pharmaceuticals at 14 sites in 11 countries.
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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Primary Hyperoxaluria Type 1, Primary Hyperoxaluria
- What is being tested?
- Lumasiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 14 sitesin 11 countries
- Study dates
- 21 Jan 2020to 23 Jun 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
14 sites in 11 countries.
14 sites in 11 countries
United States2 sites
Clinical Trial Site
Houston, Texas, 77030
Clinical Trial Site
Rochester, Minnesota, 55902
About this study
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)
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).
- Being tested
- Lumasiran
- Keywords
- PH1, Primary Hyperoxaluria, Hyperoxaluria, RNAi Therapeutic, siRNA, AGT, Systemic Oxalosis
- Medical subject headings
- Primary hyperoxaluria type 1, Hyperoxaluria, Primary, Hyperoxaluria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LumasiranDrug
Also called ALN-GO1, OXLUMO
Lumasiran will be administered by subcutaneous (SC) injection.
| Study group | Role | What they receive |
|---|---|---|
| Lumasiran | Experimental | All patients will receive open-label lumasiran. Receives: Drug: Lumasiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Month 6
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.
Measured: Baseline to Month 6
Secondary outcomes (29)
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.
Measured: Baseline to Month 6
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.
Measured: Baseline to Month 6
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.
Measured: Baseline to Month 6
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.
Measured: Baseline to Month 6
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.
Measured: Baseline to Month 6
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.
Measured: Baseline to Month 6
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.
Measured: Baseline to Month 6
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.
Measured: Baseline to Month 6
Maximum Plasma Concentration (Cmax) of Lumasiran
Cmax is the highest concentration of lumasiran in the plasma after a dose is given.
Measured: Day 1; Month 6
Time to Maximum Plasma Concentration (Tmax) of Lumasiran
Tmax is the time it takes for lumasiran to reach the maximum concentration (Cmax) after administration.
Measured: Day 1; Month 6
Elimination Half-life (t½β) of Lumasiran
t½β is the time it takes for the concentration of the drug in the plasma to be reduced by 50%.
Measured: Day 1; Month 6
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.
Measured: Day 1; Month 6
Apparent Clearance (CL/F) of Lumasiran
CL/F is the rate at which lumasiran is eliminated from the body.
Measured: Day 1; Month 6
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.
Measured: Day 1; Month 6
Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 60
Measured: Baseline to Month 60
Absolute Change in Plasma Oxalate From Baseline to Month 60
Measured: Baseline to Month 60
Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60
Measured: Baseline to Month 60
Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60
Measured: Baseline to Month 60
Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60
Measured: Baseline to Month 60
Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60
Measured: Baseline to Month 60
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.
Measured: Baseline to Month 60
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.
Measured: Baseline to Month 60
Percent Change in Plasma Oxalate From Baseline to End of Study
Measured: Baseline to Month 60
Change in Nephrocalcinosis From Baseline to End of Study
Nephrocalcinosis will be assessed by renal ultrasound.
Measured: Baseline to Month 60
Change in Frequency of Dialysis From Baseline to End of Study
Measured: Baseline to Month 60
Change in Mode of Dialysis From Baseline to End of Study
Modes of dialysis are defined as hemodialysis and peritoneal dialysis.
Measured: Baseline to Month 60
Change in Frequency of Renal Stone Events From Baseline to End of Study
Measured: Baseline to Month 60
Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) From Baseline to End of Study
Measured: Baseline to Month 60
Change in Measures of Systemic Oxalosis From Baseline to End of Study
Systemic oxalosis will be assessed in cardiac, skeletal, ophthalmologic, and dermatologic systems.
Measured: Baseline to Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2019
- Study start21 Jan 2020
- Primary completion18 May 2021
- Study completion23 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Primary Hyperoxaluria Type 1Studies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04152200
- Sponsor's protocol ID
- ALN-GO1-005
- Other IDs
- 2019-001346-17, 2023-503382-29-00, 2023, 2019
- Acronym
- ILLUMINATE-C
- Status last verified
- Jul 2025
- First submitted
- 31 Oct 2019
- Last updated
- 18 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
- Expanded access
- Available
Publications
Sankar A, Y S RK, Singh A, Roy R, Shukla R, Verma B. Next-generation therapeutics for rare genetic disorders. Mutagenesis. 2024 Apr 24;39(3):157-171. doi: 10.1093/mutage/geae002.
PubMed 38332115Michael M, Groothoff JW, Shasha-Lavsky H, Lieske JC, Frishberg Y, Simkova E, Sellier-Leclerc AL, Devresse A, Guebre-Egziabher F, Bakkaloglu SA, Mourani C, Saqan R, Singer R, Willey R, Habtemariam B, Gansner JM, Bhan I, McGregor T, Magen D. Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial. Am J Kidney Dis. 2023 Feb;81(2):145-155.e1. doi: 10.1053/j.ajkd.2022.05.012. Epub 2022 Jul 14.
PubMed 35843439