Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1
Primary Hyperoxaluria Type 1 (PH1)
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
Eligibility Criteria
Inclusion Criteria for Parts A and B:
- Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception.
- Willing to provide written informed consent and to comply with study requirements.
Additional Inclusion Criteria for Part B:
- Confirmation of PH1 disease
- Meet 24 hour urine oxalate excretion requirements
- Estimated glomerular filtration rate (GFR) of >45 mL/min/1.73m^2
- If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days
Exclusion Criteria for Parts A and B:
- Clinically significant health concerns (with the exception of PH1 for patients in Part B)
- Clinically significant electrocardiogram (ECG) abnormalities
- Abnormal for aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and any other clinical safety laboratory result considered clinically significant
- Received an investigational agent within 3 months before the first dose of study drug or are in follow-up of another clinical study
- Known history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc)
- History of intolerance to subcutaneous injection
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
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Part A: SAD: Placebo
Part A: SAD: Lumasiran 0.3 mg/kg
Part A: SAD: Lumasiran 1.0 mg/kg
Part A: SAD: Lumasiran 3.0 mg/kg
Part A: SAD: Lumasiran 6.0 mg/kg
Part B: MAD: Placebo
Part B: MAD: Lumasiran 1.0 mg/kg qM
Part B: MAD: Lumasiran 3.0 mg/kg qM
Part B: MAD: Lumasiran 3.0 mg/kg q3M
A single dose of matching placebo will be administered subcutaneously (SC).
A single dose of 0.3 mg/kg lumasiran will be administered SC.
A single dose of 1.0 mg/kg lumasiran will be administered SC.
A single dose of 3.0 mg/kg lumasiran will be administered SC.
A single dose of 6.0 mg/kg lumasiran will be administered SC.
Participants with primary hyperoxaluria type 1 (PH1) will be treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo treated participants will cross over to their respective Part B lumasiran arms in the Part B: MAD Study Day 85-End of Study Period and will then be treated with lumasiran. The estimated total time on study was up to 546 days.
Participants with PH1 will be treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.
Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.
Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.