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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03681184
Recruitment Status : Active, not recruiting
First Posted : September 21, 2018
Results First Posted : January 19, 2021
Last Update Posted : January 13, 2022
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE September 19, 2018
First Posted Date  ICMJE September 21, 2018
Results First Submitted Date  ICMJE December 22, 2020
Results First Posted Date  ICMJE January 19, 2021
Last Update Posted Date January 13, 2022
Actual Study Start Date  ICMJE November 27, 2018
Actual Primary Completion Date November 5, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
Percent change in 24-hour urinary oxalate excretion from baseline to Month 6 [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Absolute Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period [ Time Frame: Up to 60 months ]
  • Percentage Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period [ Time Frame: Up to 60 months ]
  • 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 ]
  • Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline Over Time During the Extension Period [ Time Frame: Up to 60 months ]
  • Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time During the Extension Period [ Time Frame: Up to 60 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
  • Absolute change in 24-hour urinary oxalate corrected for body surface area (BSA) from baseline to Month 6 [ Time Frame: 6 months ]
  • Change in 24-hour urinary oxalate:creatinine ratio (value/upper limit of normal [ULN]) from baseline to Month 6 [ Time Frame: 6 months ]
  • Proportion of patients with 24-hour urinary oxalate level below 1.5 x ULN at Month 6 [ Time Frame: 6 months ]
  • Proportion of patients with 24-hour urinary oxalate level below ULN at Month 6 [ Time Frame: 6 months ]
  • Change in estimated glomerular filtration rate (eGFR) from baseline to Month 6 [ Time Frame: 6 months ]
  • Frequency of adverse events [ Time Frame: From treatment initiation to study completion (approximately 6 years) ]
  • Seriousness of adverse events [ Time Frame: From treatment initiation to study completion (approximately 6 years) ]
Current Other Pre-specified Outcome Measures
 (submitted: December 22, 2020)
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Primary Hyperoxaluria Type 1 (PH1)
Intervention  ICMJE
  • Drug: Placebo
    Placebo by SC injection
  • Drug: Lumasiran
    Lumasiran by SC injection
    Other Name: ALN-GO1
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Lumasiran
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Lumasiran
Publications * Garrelfs SF, Frishberg Y, Hulton SA, Koren MJ, O'Riordan WD, Cochat P, Deschênes 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 2, 2020)
39
Original Estimated Enrollment  ICMJE
 (submitted: September 19, 2018)
30
Estimated Study Completion Date  ICMJE January 2024
Actual Primary Completion Date November 5, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Israel,   Netherlands,   Switzerland,   United Arab Emirates,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03681184
Other Study ID Numbers  ICMJE ALN-GO1-003
2018-001981-40 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alnylam Pharmaceuticals
Study Sponsor  ICMJE Alnylam Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Alnylam Pharmaceuticals
PRS Account Alnylam Pharmaceuticals
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP