Single-dose test of CITY-FXI in adults with and without Factor V Leiden or Prothrombin G20210A mutation
A Phase 1, Randomised, Double-Blind, Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CITY-FXI, a FXI Targeting siRNA, Administered Subcutaneously in Healthy Adults and Adults With Factor V Leiden or Prothrombin G20210A Mutation
This will test a single dose of CITY-FXI, an siRNA that lowers Factor XI, in healthy adults and in adults who carry Factor V Leiden or the prothrombin G20210A mutation to see if it is safe and how it acts in the body.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 128 (estimated) |
| Ages | 18 Years to 60 Years |
| Sex | All |
| Sponsor | City Therapeutics Industry-sponsored |
| Locations | 1 site (London) |
| Trial ID | NCT07430397 on ClinicalTrials.gov |
What this trial studies
This is a first-in-human, randomized, double-blind, placebo-controlled single ascending dose trial conducted at one center. It includes two parts: ascending single doses in healthy volunteers and ascending single doses in adults with confirmed Factor V Leiden or prothrombin G20210A mutation. The main goals are to characterize safety, tolerability, pharmacokinetics, and pharmacodynamics after a single administration of CITY-FXI compared with placebo. Participants are monitored for adverse events, blood markers of coagulation, and drug levels over a defined follow-up period.
Who should consider this trial
Good fit: Ideal participants are adults (Part A: ages 18–45 non-childbearing potential; Part B: ages 18–60) with BMI 18–25 kg/m2 who can comply with study procedures, and Part B participants must have genetically confirmed Factor V Leiden or prothrombin G20210A mutation.
Not a fit: Patients with active bleeding disorders, a history of clinically significant spontaneous bleeding, homozygous or combined thrombophilic defects, significant systemic diseases, pregnant or breastfeeding individuals, or those outside the age/weight/BMI criteria are unlikely to qualify or benefit from this early single-dose trial.
Why it matters
Potential benefit: If successful, CITY-FXI could offer a new way to reduce clotting risk by lowering Factor XI activity, potentially with less bleeding than current anticoagulants.
How similar studies have performed: Previous clinical programs targeting Factor XI (using antisense oligonucleotides, antibodies, and other inhibitors) have shown promising reductions in thrombosis with relatively low bleeding rates, but CITY-FXI as an siRNA is being tested in humans for the first time.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Males and women of non-childbearing potential (WONCBP) aged 18 to 45 years (Part A only) * Male and female participants aged 18 to 60 (Part B only) * Body Mass Index (BMI) between 18 and 25 kg/m2 (inclusive) and a minimum weight of 50 kg * Ability and willingness to comply fully with all study procedures and lifestyle considerations * Confirmed diagnosis of FVL or prothrombin G20210A mutation via genetic testing (Part B only) * Women of childbearing potential (WOCBP) must agree to use acceptable highly effective contraceptive methods (Part B only) Exclusion Criteria: * Any clinically significant systemic disease or disorder, including but not limited to cardiovascular, hepatic, or oncological conditions * History or evidence of any bleeding disorders * History of clinically significant spontaneous bleeding * Prior treatment with an investigational agent * Confirmed diagnosis of homozygous mutations, or combined thrombophilic defects of (Part B only)
Where this trial is running
London
- Richmond Pharmacology — London, United Kingdom (Recruiting)
Study contacts
- Study coordinator: City Therapeutics
- Email: clinicaltrials@citytx.com
- Phone: 857-219-5440
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.