Phase 2
N=32
Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1
Primary Hyperoxaluria Type 1 (PH1)
Bottom Line
View on ClinicalTrials.gov: NCT02706886 ↗Enrolled (actual)
32
Serious AEs
9.1%
Results posted
Jan 2020
Primary outcome: Primary: Number of Participants With Adverse Events (AEs) — 5; 6; 2; 6 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lumasiran (Drug); Placebo (Drug)
- Age
- Pediatric, Adult · 6+ yrs
- Sex
- All
- Sponsor
- Alnylam Pharmaceuticals
- Primary completion
- Jan 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) |
5; 6; 2; 6; 6; 2 | — |
| SECONDARY Maximum Concentration (Cmax) of Lumasiran in Plasma |
39.7940; 204.3748; 533.4527; 1176.1302; 324.1386; 582.4515 | — |
| SECONDARY Time to Cmax (Tmax) of Lumasiran in Plasma |
5.0167; 1.5000; 3.0000; 7.0000; 3.9917; 4.9917 | — |
| SECONDARY Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma |
293.5232; 1899.8119; 7211.5890; 16778.0579; 1428.0412; 7400.2181 | — |
| SECONDARY Terminal Half-life (t1/2) of Lumasiran in Plasma |
7.0655; 5.9798; 3.4683; 3.2670; 5.4574; 7.8028 | — |
| SECONDARY Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran |
17.4219; 19.0713; 21.0472; 25.7931; 11.0895; 11.1877 | — |
| SECONDARY Renal Clearance (CLR) of Lumasiran |
8.7817; 5.4906; 5.8211; 6.3417; 2.2612; 2.3818 | — |
| SECONDARY Baseline Plasma Glycolate Concentration |
5.1; 5.3; 5.7; 6.2; 4.8 | — |
| SECONDARY Percentage Change From Baseline in Plasma Glycolate Concentration |
18.3; 58.3; 48.5; 56.4; 59.5; 22.4 | — |
| SECONDARY Baseline Spot Urine Glycolate:Creatinine Ratio in Part A |
12.4; 15.7; 15.7; 13.0; 14.8 | — |
| SECONDARY Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A |
8.1; 32.5; 82.9; 109.1; 210.5; 73.8 | — |
| SECONDARY Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B |
1.96; 1.73; 1.84; 1.30 | — |
| SECONDARY Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B |
-2.4; -41.1; -57.5; -49.2; -27.8; -49.7 | — |
| SECONDARY Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days |
193; 241; 289; 281 | — |
| SECONDARY Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days |
-15.1; 53.1; 31.4; 33.0; -13.8; 82.3 | — |
| SECONDARY Baseline Creatinine Clearance Corrected for BSA in Part B |
64.389; 108.149; 86.268; 88.251 | — |
| SECONDARY Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B |
9.019; -6.672; -0.624; 2.748; 20.184; -8.426 | — |
Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of lumasiran in healthy adult volunteers and subjects with primary hyperoxaluria type 1 (PH1). In Part A, single ascending dose (SAD) part, healthy adults were dosed with lumasiran or placebo once. In Part B, multiple ascending doses (MAD) part, patients with primary hyperoxaluria type 1 (PH1) were dosed with lumasiran or placebo. All patients that initially received placebo received lumasiran after completing placebo dosing.
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
Data sourced from ClinicalTrials.gov (NCT02706886). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.