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Trial record 1 of 1 for:    NCT04152200
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A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1 (ILLUMINATE-C)

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: NCT04152200
Recruitment Status : Active, not recruiting
First Posted : November 5, 2019
Results First Posted : July 12, 2022
Last Update Posted : November 9, 2022
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Brief 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).

Condition or disease Intervention/treatment Phase
Primary Hyperoxaluria Type 1 Primary Hyperoxaluria 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 : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : January 21, 2020
Actual Primary Completion Date : May 18, 2021
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Lumasiran

Arm Intervention/treatment
Experimental: Lumasiran
All patients will receive open-label lumasiran.
Drug: Lumasiran
Lumasiran will be administered by subcutaneous (SC) injection.
Other Names:
  • ALN-GO1
  • OXLUMO




Primary Outcome Measures :
  1. Cohort A: Percent 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. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran.

  2. Cohort B: Percent Change in Pre-dialysis 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. 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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: 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.

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

  3. Cohort A: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (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. 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.

  4. Cohort A: 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. Baseline is defined as the mean of all assessments prior to the first dose date/time of lumasiran.

  5. Cohort A: Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 [ Time Frame: 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.

  6. Cohort A: Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 [ Time Frame: 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.

  7. 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 [ Time Frame: Baseline to Month 6 ]
    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.

  8. 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 [ Time Frame: Baseline to Month 6 ]
    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.

  9. Maximum Plasma Concentration (Cmax) of Lumasiran [ Time Frame: Day 1; Month 6 ]
    Cmax is the highest concentration of lumasiran in the plasma after a dose is given.

  10. Time to Maximum Plasma Concentration (Tmax) of Lumasiran [ Time Frame: Day 1; Month 6 ]
    Tmax is the time it takes for lumasiran to reach the maximum concentration (Cmax) after administration.

  11. Elimination Half-life (t½β) of Lumasiran [ Time Frame: Day 1; Month 6 ]
    t½β is the time it takes for the concentration of the drug in the plasma to be reduced by 50%.

  12. Area Under the Concentration-time Curve From 0 to 24 Hours [AUC(0-24)] for Lumasiran [ Time Frame: Day 1; Month 6 ]
    AUC(0-24) is the area under the plasma concentration-time curve over the last 24-h dosing interval.

  13. Apparent Clearance (CL/F) of Lumasiran [ Time Frame: Day 1; Month 6 ]
    CL/F is the rate at which lumasiran is eliminated from the body.

  14. Apparent Volume of Distribution (V/F) of Lumasiran [ Time Frame: Day 1; Month 6 ]
    V/F is the propensity of lumasiran to either remain in the plasma or redistribute to other tissues.

  15. Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 60 [ Time Frame: Baseline to Month 60 ]
  16. Absolute Change in Plasma Oxalate From Baseline to Month 60 [ Time Frame: Baseline to Month 60 ]
  17. Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60 [ Time Frame: Baseline to Month 60 ]
  18. Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60 [ Time Frame: Baseline to Month 60 ]
  19. Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60 [ Time Frame: Baseline to Month 60 ]
  20. Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60 [ Time Frame: Baseline to Month 60 ]
  21. 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 [ Time Frame: Baseline to Month 60 ]
    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.

  22. 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 [ Time Frame: Baseline to Month 60 ]
    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.

  23. Percent Change in Plasma Oxalate From Baseline to End of Study [ Time Frame: Baseline to Month 60 ]
  24. Change in Nephrocalcinosis From Baseline to End of Study [ Time Frame: Baseline to Month 60 ]
    Nephrocalcinosis will be assessed by renal ultrasound.

  25. Change in Frequency of Dialysis From Baseline to End of Study [ Time Frame: Baseline to Month 60 ]
  26. Change in Mode of Dialysis From Baseline to End of Study [ Time Frame: Baseline to Month 60 ]
    Modes of dialysis are defined as hemodialysis and peritoneal dialysis.

  27. Change in Frequency of Renal Stone Events From Baseline to End of Study [ Time Frame: Baseline to Month 60 ]
  28. Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) From Baseline to End of Study [ Time Frame: Baseline to Month 60 ]
  29. Change in Measures of Systemic Oxalosis From Baseline to End of Study [ Time Frame: Baseline to Month 60 ]
    Systemic oxalosis will be assessed in cardiac, skeletal, ophthalmologic, and dermatologic systems.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

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): NCT04152200


Locations
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United States, Minnesota
Clinical Trial Site
Rochester, Minnesota, United States, 55902
United States, Texas
Clinical Trial Site
Houston, Texas, United States, 77030
Australia
Clinical Trial Site
Garran, Australia
Belgium
Clinical Trial Site
Brussels, Belgium
France
Clinical Trial Site
Bron, France
Clinical Trial Site
Lyon, France
Israel
Clinical Trial Site
Haifa, Israel
Clinical Trial Site
Nahariya, Israel
Italy
Clinical Trial Site
Rome, Italy
Jordan
Clinical Trial Site
Irbid, Jordan
Lebanon
Clinical Trial Site
Beirut, Lebanon
Netherlands
Clinical Trial Site
Amsterdam, Netherlands
Turkey
Clinical Trial Site
Yenimahalle, Turkey
United Arab Emirates
Clinical Trial Site
Dubai, United Arab Emirates
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Medical Director Alnylam Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alnylam Pharmaceuticals:
Study Protocol  [PDF] May 6, 2020
Statistical Analysis Plan  [PDF] March 15, 2021

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04152200    
Other Study ID Numbers: ALN-GO1-005
2019-001346-17 ( EudraCT Number )
First Posted: November 5, 2019    Key Record Dates
Results First Posted: July 12, 2022
Last Update Posted: November 9, 2022
Last Verified: November 2022
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
Hyperoxaluria
RNAi Therapeutic
siRNA
AGT
Systemic Oxalosis
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
Lumasiran
Renal Agents