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A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1 (ILLUMINATE-A)

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ClinicalTrials.gov Identifier: NCT03681184
Recruitment Status : Active, not recruiting
First Posted : September 21, 2018
Results First Posted : January 19, 2021
Last Update Posted : June 16, 2021
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Brief 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).

Condition or disease Intervention/treatment Phase
Primary Hyperoxaluria Type 1 (PH1) Drug: Placebo Drug: Lumasiran Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 27, 2018
Actual Primary Completion Date : November 5, 2019
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
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.
Drug: Placebo
Placebo by SC injection

Drug: Lumasiran
Lumasiran by SC injection
Other Name: ALN-GO1

Experimental: Lumasiran
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.
Drug: Placebo
Placebo by SC injection

Drug: Lumasiran
Lumasiran by SC injection
Other Name: ALN-GO1




Primary Outcome Measures :
  1. 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 ]
    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.


Secondary Outcome Measures :
  1. Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6 [ Time Frame: 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.

  2. Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 [ Time Frame: 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.

  3. Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6 [ Time Frame: Month 6 ]
    The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA.

  4. Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6 [ Time Frame: Month 6 ]
    The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA.

  5. Percentage Change in Plasma Oxalate From Baseline to Month 6 [ Time Frame: 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.

  6. Absolute Change in Plasma Oxalate From Baseline to Month 6 [ Time Frame: 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.

  7. Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6 [ Time Frame: Baseline, Week 2, 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.

  8. Absolute Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period [ Time Frame: Up to 60 months ]
  9. Percentage Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period [ Time Frame: Up to 60 months ]
  10. Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During the Extension Period [ Time Frame: Up to 60 months ]
  11. Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline Over Time During the Extension Period [ Time Frame: Up to 60 months ]
  12. Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time During the Extension Period [ Time Frame: Up to 60 months ]

Other Outcome Measures:
  1. Rate of Renal Stone Events [ Time Frame: 12-Month Period prior to Informed Consent, 6-Month DB Period ]
    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.

  2. Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound [ Time Frame: Baseline, Month 6 ]
    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.



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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03681184


Locations
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United States, California
Clinical Trial Site
San Diego, California, United States, 92120
United States, Florida
Clinical Trial Site
Jacksonville, Florida, United States, 32216
United States, Minnesota
Clinical Trial Site
Rochester, Minnesota, United States, 55905
United States, New York
Clinical Trial Site
New York, New York, United States, 10029
France
Clinical Trial Site
Lyon, France
Clinical Trial Site
Paris, France
Germany
Clinical Trial Site
Bonn, Germany
Israel
Clinical Trial Site
Haifa, Israel
Clinical Trial Site
Jerusalem, Israel
Clinical Trial Site
Nahariya, Israel
Netherlands
Clinical Trial Site
Amsterdam, Netherlands
Switzerland
Clinical Trial Site
Bern, Switzerland
United Arab Emirates
Clinical Trial Site
Dubai, United Arab Emirates
United Kingdom
Clinical Trial Site
Birmingham, United Kingdom
Clinical Trial Site
London, United Kingdom, NW3 2QG
Clinical Trial Site
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: Medical Director Alnylam Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alnylam Pharmaceuticals:
Study Protocol  [PDF] March 19, 2019
Statistical Analysis Plan  [PDF] November 21, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03681184    
Other Study ID Numbers: ALN-GO1-003
2018-001981-40 ( EudraCT Number )
First Posted: September 21, 2018    Key Record Dates
Results First Posted: January 19, 2021
Last Update Posted: June 16, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alnylam Pharmaceuticals:
PH1
Primary hyperoxaluria
RNAi therapeutic
siRNA
AGT
Oxalate
Additional relevant MeSH terms:
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Hyperoxaluria, Primary
Hyperoxaluria
Kidney Diseases
Urologic Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases