Primary Hyperoxaluria Type 1 (PH1)Phase 3ILLUMINATE-ANCT03681184
A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1
A Phase 3 study testing Lumasiran in people with Primary Hyperoxaluria Type 1 (PH1), run by Alnylam Pharmaceuticals at 17 sites in 8 countries.
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). Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Primary Hyperoxaluria Type 1 (PH1)
- What is being tested?
- Lumasiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 17 sitesin 8 countries
- Study dates
- 27 Nov 2018to 12 Jan 2024
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
17 sites in 8 countries.
17 sites in 8 countries
United States5 sites
Clinical Trial Site
Cleveland, Ohio, 44195
Clinical Trial Site
Jacksonville, Florida, 32216
Clinical Trial Site
New York, New York, 10029
Clinical Trial Site
Rochester, Minnesota, 55905
Clinical Trial Site
San Diego, California, 92120
Israel3 sites
Clinical Trial Site
Haifa
Clinical Trial Site
Jerusalem
Clinical Trial Site
Nahariya
United Kingdom3 sites
Clinical Trial Site
Birmingham
Clinical Trial Site
London, NW3 2QG
Clinical Trial Site
London, WC1N 3JH
About this study
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
The purpose of this study is to evaluate the efficacy and safety of lumasiran in children and adults with primary hyperoxaluria type 1 (PH1).
- Conditions
- Primary Hyperoxaluria Type 1 (PH1)
- Being tested
- Placebo, Lumasiran
- Keywords
- PH1, Primary hyperoxaluria, RNAi therapeutic, siRNA, AGT, Oxalate
- Medical subject headings
- Primary hyperoxaluria type 1, Hyperoxaluria, Primary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo by SC injection
LumasiranDrug
Also called ALN-GO1
Lumasiran by SC injection
| Study group | Role | What they receive |
|---|---|---|
| Placebo/Lumasiran | Placebo comparator | Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period. Receives: Drug: Placebo; Drug: Lumasiran |
| Lumasiran/Lumasiran | Experimental | Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period. Receives: Drug: Placebo; Drug: Lumasiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Month 6
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Month 6
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Baseline to Month 54 and Month 60
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline in the Extension Period
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.
Measured: 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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2018
- Study start27 Nov 2018
- Primary completion5 Nov 2019
- Study completion12 Jan 2024
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 1 (PH1)Studies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 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
- NCT03681184
- Sponsor's protocol ID
- ALN-GO1-003
- Other IDs
- 2018-001981-40, 2018
- Acronym
- ILLUMINATE-A
- Status last verified
- Jul 2024
- First submitted
- 19 Sep 2018
- Last updated
- 12 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Frishberg Y, Saland JM, Lieske JC, Du W, Coenen M, Hogan J, Sellier-Leclerc AL, Groothoff JW, Kaspar C, Gansner JM, Hulton SA; ILLUMINATE-A study investigators. Final Results of the ILLUMINATE-A Phase 3 Clinical Trial of Lumasiran for Primary Hyperoxaluria 1. Clin J Am Soc Nephrol. 2026 Mar 1;21(3):377-388. doi: 10.2215/CJN.0000000916. Epub 2025 Dec 4.
PubMed 41343248Garrelfs SF, Frishberg Y, Hulton SA, Koren MJ, O'Riordan WD, Cochat P, Deschenes G, Shasha-Lavsky H, Saland JM, Van't Hoff WG, Fuster DG, Magen D, Moochhala SH, Schalk G, Simkova E, Groothoff JW, Sas DJ, Meliambro KA, Lu J, Sweetser MT, Garg PP, Vaishnaw AK, Gansner JM, McGregor TL, Lieske JC; ILLUMINATE-A Collaborators. Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1. N Engl J Med. 2021 Apr 1;384(13):1216-1226. doi: 10.1056/NEJMoa2021712.
PubMed 33789010