Prevention & lipidsRandomised controlled trial
Safety and lipoprotein(a)-lowering effects of Kylo-11, a non-canonical, long-duration small interfering RNA targeting lipoprotein(a): a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial
- Randomised controlled trial
- first-in-human
- double-blind
- placebo-controlled
- phase 1
- single-centre
- 7 dosing cohorts
- Median follow-up 337 days (IQR 334-337)
Authors' conclusion
A single dose of Kylo-11 was well tolerated, and at doses of 225 mg or higher, durably reduced serum lipoprotein(a) concentrations up to 48 weeks.
Study context
- Population
- Otherwise healthy adults aged 18–55 years with elevated lipoprotein(a), single site in China70 received a dose
- Participants
- 71 adults
- Comparison
- Single SC dose of Kylo-11 vs placebo
- Kylo-11n = 57
- Placebon = 14reference
- Primary endpoint
- Incidence of investigator-assessed adverse events
- Follow-up
- Up to 24 weeks
Primary result
As reported in the abstract
Adverse events (all participants)
Participants with adverse events, mostly grade 1-2 and unrelated to study drug
37 (53%) of 70
Secondary outcomes
| Outcome | Values |
|---|---|
| Median percent reduction in serum Lp(a) (prespecified pharmacodynamic secondary endpoint) · 48 weeks (final follow-up) | 9 mg median −53 (IQR −71–-41) % · 600 mg median −97 (IQR −98–-97) % · Cohort 7 (225 mg) median −96 (IQR −98–-91) % |
| Median absolute reduction in serum Lp(a) (prespecified pharmacodynamic secondary endpoint) · 48 weeks (final follow-up) | 9 mg median −71 (IQR −79–-60) nmol/L · 600 mg median −129 (IQR −153–-99) nmol/L · Cohort 7 (225 mg) median −208 (IQR −222–-198) nmol/L |
- Median percent reduction in serum Lp(a) (prespecified pharmacodynamic secondary endpoint): Kylo-11 groups ranged from the 9 mg cohort to the 600 mg cohort
- Median percent reduction in serum Lp(a) (prespecified pharmacodynamic secondary endpoint): Cohort 7: baseline Lp(a) >200 nmol/L
- Median absolute reduction in serum Lp(a) (prespecified pharmacodynamic secondary endpoint): Kylo-11 groups ranged from the 9 mg cohort to the 600 mg cohort
- Median absolute reduction in serum Lp(a) (prespecified pharmacodynamic secondary endpoint): Cohort 7: baseline Lp(a) >200 nmol/L
Safety
Serious, drug-related and grade ≥3 adverse events
- Injection-site reactions, serious AEs, drug-related AEs, deaths
- 0
- Grade ≥3 events in 225 mg cohort (hypertriglyceridaemia, elevated CPK at day 168), unrelated to study drug
- 2
- Grade ≥3 event in placebo (transient hypertriglyceridaemia, day 84)
- 1
Original publication
Safety and lipoprotein(a)-lowering effects of Kylo-11, a non-canonical, long-duration small interfering RNA targeting lipoprotein(a): a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial. Lancet. Published 28 August 2026. doi:10.1016/s0140-6736(26)01484-4
Summarised from the published abstract; every number is checked against it