search
Back to results

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

Primary Purpose

Primary Hyperoxaluria Type 1 (PH1)

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Lumasiran
Sponsored by
Alnylam Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Hyperoxaluria Type 1 (PH1) focused on measuring PH1, Primary hyperoxaluria, RNAi therapeutic, siRNA, AGT, Oxalate

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Lumasiran

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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 <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
Percentage Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period
Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During the Extension Period
Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline Over Time During the Extension Period
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time During the Extension Period

Full Information

First Posted
September 19, 2018
Last Updated
September 6, 2023
Sponsor
Alnylam Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT03681184
Brief Title
A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1
Acronym
ILLUMINATE-A
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 27, 2018 (Actual)
Primary Completion Date
November 5, 2019 (Actual)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Hyperoxaluria Type 1 (PH1)
Keywords
PH1, Primary hyperoxaluria, RNAi therapeutic, siRNA, AGT, Oxalate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Lumasiran
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo by SC injection
Intervention Type
Drug
Intervention Name(s)
Lumasiran
Other Intervention Name(s)
ALN-GO1
Intervention Description
Lumasiran by SC injection
Primary Outcome Measure Information:
Title
Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
Description
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.
Time Frame
Baseline to Month 6
Secondary Outcome Measure Information:
Title
Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6
Description
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.
Time Frame
Baseline to Month 6
Title
Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
Description
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.
Time Frame
Baseline to Month 6
Title
Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6
Description
The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA.
Time Frame
Month 6
Title
Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6
Description
The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA.
Time Frame
Month 6
Title
Percentage Change in Plasma Oxalate From Baseline to Month 6
Description
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.
Time Frame
Baseline to Month 6
Title
Absolute Change in Plasma Oxalate From Baseline to Month 6
Description
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.
Time Frame
Baseline to Month 6
Title
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6
Description
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.
Time Frame
Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6
Title
Absolute Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period
Time Frame
Up to 60 months
Title
Percentage Change in 24-hour Urinary Oxalate Excretion From Baseline Over Time During the Extension Period
Time Frame
Up to 60 months
Title
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
Title
Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline Over Time During the Extension Period
Time Frame
Up to 60 months
Title
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time During the Extension Period
Time Frame
Up to 60 months
Other Pre-specified Outcome Measures:
Title
Rate of Renal Stone Events
Description
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.
Time Frame
12-Month Period prior to Informed Consent, 6-Month DB Period
Title
Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound
Description
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.
Time Frame
Baseline, Month 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
Clinical Trial Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Clinical Trial Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Clinical Trial Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Clinical Trial Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Clinical Trial Site
City
Lyon
Country
France
Facility Name
Clinical Trial Site
City
Paris
Country
France
Facility Name
Clinical Trial Site
City
Bonn
Country
Germany
Facility Name
Clinical Trial Site
City
Haifa
Country
Israel
Facility Name
Clinical Trial Site
City
Jerusalem
Country
Israel
Facility Name
Clinical Trial Site
City
Nahariya
Country
Israel
Facility Name
Clinical Trial Site
City
Amsterdam
Country
Netherlands
Facility Name
Clinical Trial Site
City
Bern
Country
Switzerland
Facility Name
Clinical Trial Site
City
Dubai
Country
United Arab Emirates
Facility Name
Clinical Trial Site
City
Birmingham
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33789010
Citation
Garrelfs 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.
Results Reference
derived

Learn more about this trial

A Study to Evaluate Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1

We'll reach out to this number within 24 hrs