A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1 (ILLUMINATE-C)

• ClinicalTrials.gov Identifier: NCT04152200
• Recruitment Status: Not yet recruiting
• First Posted: November 5, 2019
• Last Update Posted: November 5, 2019
• Sponsor: Alnylam Pharmaceuticals
• Information provided by (Responsible Party): Alnylam Pharmaceuticals

Tracking Information

• First Submitted Date: October 31, 2019
• First Posted Date: November 5, 2019
• Last Update Posted Date: November 5, 2019
• Estimated Study Start Date: November 2019
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 4, 2019)

• Percent Change in Plasma Oxalate from Baseline to Month 6 [ Time Frame: Baseline, Month 6 ]
• Percent Change in Pre-dialysis Plasma Oxalate from Baseline to Month 6 [ Time Frame: Baseline, Month 6 ]

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: November 4, 2019)

• Percent Change in Plasma Oxalate Area Under the Curve (AUC) Between Dialysis Sessions from Baseline to Month 6 and Month 60 [ Time Frame: Baseline, Month 6; Baseline, Month 60 ]
• Absolute Change in Plasma Oxalate from Baseline to Month 6 and Month 60 [ Time Frame: Baseline, Month 6; Baseline, Month 60 ]
• Change in Urinary Oxalate from Baseline to Month 6 and Month 60 [ Time Frame: Baseline, Month 6; Baseline, Month 60 ]
• Change in Quality of Life As Assessed by Pediatric Quality of Life Inventory (PedsQL) Total Score from Baseline to Month 6 and Month 60 [ Time Frame: Baseline, Month 6; Baseline, Month 60 ]
  Measures core dimensions of health plus role (school) functioning in children. Total score range: 0 - 100; higher scores indicate better health-related quality of life (HRQoL).
• Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) from Baseline to Month 6 and Month 60 [ Time Frame: Baseline, Month 6; Baseline, Month 60 ]
  KDQOL-36 is a kidney disease-specific measure of HRQoL. Score range (per domain): 0 - 100; higher scores indicate better HRQoL.
• Maximum Plasma Concentration (Cmax) of Lumasiran [ Time Frame: Baseline, Month 6 ]
• Time to Maximum Plasma Concentration (tmax) of Lumasiran [ Time Frame: Baseline, Month 6 ]
• Elimination Half-life (t½β) of Lumasiran [ Time Frame: Baseline, Month 6 ]
• Area Under the Concentration-time Curve (AUC) of Lumasiran [ Time Frame: Baseline, Month 6 ]
• Apparent Clearance (CL/F) of Lumasiran [ Time Frame: Baseline, Month 6 ]
• Apparent Volume of Distribution (V/F) of Lumasiran [ Time Frame: Baseline, Month 6 ]
• Percent Change in Plasma Oxalate from Baseline to End of Study [ Time Frame: Baseline, Month 60 ]
• Change in Nephrocalcinosis from Baseline to End of Study [ Time Frame: Baseline, Month 60 ]
  Nephrocalcinosis will be assessed by renal ultrasound.
• Change in Frequency of Dialysis from Baseline to End of Study [ Time Frame: Baseline, Month 60 ]
• Change in Mode of Dialysis from Baseline to End of Study [ Time Frame: Baseline, Month 60 ]
  Modes of dialysis are defined as hemodialysis and peritoneal dialysis.
• Change in Frequency of Renal Stone Events from Baseline to End of Study [ Time Frame: Baseline, Month 60 ]
• Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) from Baseline to End of Study [ Time Frame: Baseline, Month 60 ]
• Change in Measures of Systemic Oxalosis from Baseline to End of Study [ Time Frame: Baseline, Month 60 ]
  Systemic oxalosis will be assessed in cardiac, skeletal, ophthalmologic, and dermatologic systems.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1
• 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)
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Primary Hyperoxaluria Type 1
• Primary Hyperoxaluria

Intervention

Drug: Lumasiran

Lumasiran will be administered by subcutaneous (SC) injection.

Other Name: ALN-GO1

Study Arms

Experimental: Lumasiran

All participants will receive open-label lumasiran.

Intervention: Drug: Lumasiran

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: November 4, 2019): 16
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Has documented diagnosis of primary hyperoxaluria type 1 (PH1)
• Estimated glomerular filtration rate (eGRF) ≤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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Alnylam Clinical Trial Information Line; 1-877-ALNYLAM; clinicaltrials@alnylam.com

Contact: Alnylam Clinical Trial Information Line; 1-877-256-9526; clinicaltrials@alnylam.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04152200
• Other Study ID Numbers: ALN-GO1-005; 2019-001346-17 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

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

• Plan to Share IPD: No

• Responsible Party: Alnylam Pharmaceuticals
• Study Sponsor: Alnylam Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Tracy McGregor, MD; Alnylam Pharmaceuticals

• PRS Account: Alnylam Pharmaceuticals
• Verification Date: November 2019