Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a)): A Randomized Dose-Ascending Clinical Trial
Authors' conclusion
In this phase 1 study of 48 participants with elevated lipoprotein(a) levels, lepodisiran was well tolerated and produced dose-dependent, long-duration reductions in serum lipoprotein(a) concentrations.
Study context
- Population
- Adults without CVD with lipoprotein(a) ≥75 nmol/L (or ≥30 mg/dL)
- Participants
- 48 adults
- Comparison
- Single-dose lepodisiran vs placebo
- Primary endpoint
- Safety and tolerability of single ascending doses of lepodisiran
Methodological detailsphase 1, single ascending-dose, placebo-controlled, 5 sites in the US and Singapore
- Phase 1
- Single ascending-dose
- Placebo-controlled
- 5 sites in the US and Singapore
Primary result
As reported in the abstract
Safety and tolerability
Serious adverse events (all participants)
1
Secondary outcomes
| Outcome | Values |
|---|---|
| Maximal median change in lipoprotein(a) | Placebo median −5% (IQR −16%–11%) · 4 mg median −41% (IQR −47%–-20%) · 12 mg median −59% (IQR −66%–-53%) · 32 mg median −76% (IQR −76%–-75%) · 96 mg median −90% (IQR −94%–-85%) · 304 mg median −96% (IQR −98%–-95%) · 608 mg median −97% (IQR −98%–-96%) |
| Median change in lipoprotein(a) · day 337 | 608 mg median −94% (IQR −94%–-85%) |
Plasma lepodisiran pharmacokinetics
Hours
- Peak plasma levels reached within
- 10.5
- Undetectable by
- 48
Safety
Serious adverse events
- Serious adverse events (all participants)
- 1
Original publication
Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a)): A Randomized Dose-Ascending Clinical Trial. JAMA. Published 5 December 2023. doi:10.
Summarised from the published abstract; every number is checked against it