Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a)): A Randomized Clinical Trial
Authors' conclusion
Zerlasiran was well tolerated and reduced lipoprotein(a) concentrations with infrequent administration.
Study context
- Population
- Healthy participants (single dose) and patients with stable atherosclerotic cardiovascular disease (ASCVD) (multiple dose) with lipoprotein(a) >150 nmol/L; 7 sites in US, Netherlands, UK and Australia, 2020–202336 of 37 completed (multiple dose)
- Participants
- 8 / 6 / 6 / 9 / 9 / 9 / 9
- Comparison
- Zerlasiran) vs placebo
- Placebo (single dose)n = 8reference
- Zerlasiran 300 mg (single dose)n = 6
- Zerlasiran 600 mg (single dose)n = 6
- Placebo (2 doses)n = 9reference
- Zerlasiran 200 mgn = 9
- Zerlasiran 300 mgn = 9
- Zerlasiran 450 mgn = 9
- Primary endpoint
- Safety and tolerability
Methodological detailssingle ascending dose, multiple-dose, placebo-controlled, multicentre (7 sites)
- Single ascending dose
- Multiple-dose
- Placebo-controlled
- Multicentre (7 sites)
Primary result
As reported in the abstract
Serious adverse events
0
Secondary outcomes
| Outcome | Values |
|---|---|
| Median change in lipoprotein(a), single dose · 365 days | Placebo (single dose) median 14% (IQR 13%–15%) · Zerlasiran 300 mg (single dose) median −30% (IQR −51%–-18%) · Zerlasiran 600 mg (single dose) median −29% (IQR −39%–-7%) |
| Maximal median change in lipoprotein(a), after 2 doses | Placebo (2 doses) median 19 (IQR −17–28) nmol/L · Maximal median percent change 7% (IQR, −4% to 21%) · Zerlasiran 200 mg median −258 (IQR −289–-188) nmol/L · Maximal median percent change −97% (IQR, −98% to −95%) · Zerlasiran 300 mg median −310 (IQR −368–-274) nmol/L · Maximal median percent change −98% (IQR, −99% to −97%) · Zerlasiran 450 mg median −242 (IQR −343–-182) nmol/L · Maximal median percent change −99% (IQR, −99% to −98%) |
| Median percent change in lipoprotein(a), after 2 doses · 201 days after administration | Placebo (2 doses) median 0.3% (IQR −2%–21%) · Zerlasiran 200 mg median −60% (IQR −71%–-40%) · Zerlasiran 300 mg median −90% (IQR −91%–-74%) · Zerlasiran 450 mg median −89% (IQR −91%–-76%) |
- Maximal median change in lipoprotein(a), after 2 doses: baseline median 288 (IQR, 199-352) nmol/L
Safety
Serious adverse events
- No serious adverse events
Original publication
Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a)): A Randomized Clinical Trial. JAMA. Published 14 May 2024. doi:10.
Summarised from the published abstract; every number is checked against it