Factor V LeidenPhase 1NCT07430397
A Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CITY-FXI in Healthy Adults, Adults With FV Leiden or Prothrombin G20210A Mutation, and Adults With a History of Provoked Venous Thromboembolism
A Phase 1 study testing CITY-FXI in people with Factor V Leiden and Prothrombin G20210A, run by City Therapeutics at 1 site in United Kingdom.
Trial summary
This is a first-in-human (FIH), single-center, randomized, double-blind, placebo-controlled, single ascending and multiple dose study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CITY-FXI in healthy adults, adults with Factor V Leiden (FVL) or prothrombin G20210A mutation… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Factor V Leiden, Prothrombin G20210A, Venous Thromboembolism (VTE)
- What is being tested?
- CITY-FXI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 182 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 22 Jan 2026to Apr 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males and women of non-childbearing potential (WONCBP) aged 18 to 45 years (inclusive, for Part A only)
- Male and female participants aged 18 to 60 (inclusive, for Part B only), and aged 18 to 65 years (inclusive, for Part C only)
- Body Mass Index (BMI) between 18 and 25 kg/m2 (inclusive, for Part B only) and 18 and 35 kg/m2 (inclusive, for Part C only) and a minimum weight of 50 kg (Parts A, B, and C)
- 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 (Parts B and C only)
- History of provoked venous thromboembolism (VTE) within the last 10 years and/or confirmed diagnosis of heterozygosity for FVL and prothrombin G20210A mutation via genetic testing (Part C only)
Who cannot join
- 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 (e.g., FVL with prothrombin G20210A mutation) (Parts B and C only)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Richmond Pharmacology
London, SE1 1YR
Dr. Ulrike Lorch, +44 0207 042 5800, volunteer@richmondpharmacology.com
About this study
Official title: 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, Adults With Factor V Leiden or Prothrombin G20210A Mutation, and Adults With a History of Provoked Venous Thromboembolism
This is a first-in-human (FIH), single-center, randomized, double-blind, placebo-controlled, single ascending and multiple dose study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CITY-FXI in healthy adults, adults with Factor V Leiden (FVL) or prothrombin G20210A mutation, and adults with a history of provoked venous thromboembolism (VTE).
Read the detailed description
The study will be conducted in three parts:
- Part A: Single Ascending Dose in Healthy Adults
- Part B: Single Ascending Dose in Adults with Factor V Leiden (FVL) or Prothrombin G20210A Mutation
- Part C: Multiple Doses in Adults with FVL or Prothrombin G20210A Mutation and/or a History of Provoked Venous Thromboembolism (VTE)
- Being tested
- CITY-FXI, Placebo
- Keywords
- Factor XI, siRNA
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CITY-FXIDrug
siRNA (subcutaneous injection)
PlaceboDrug
Saline (subcutaneous injection)
| Study group | Role | What they receive |
|---|---|---|
| CITY-FXI in Healthy Adults (Part A) | Experimental | Not described Receives: Drug: CITY-FXI |
| In Healthy Adults (Part A) | Placebo comparator | Not described Receives: Drug: Placebo |
| CITY-FXI in Adults with Factor V Leiden or Prothrombin G20210A Mutation (Part B) | Experimental | Not described Receives: Drug: CITY-FXI |
| In Adults with Factor V Leiden or Prothrombin G20210A Mutation (Part B) | Placebo comparator | Not described Receives: Drug: Placebo |
| CITY-FXI in Adults with FVL, Prothrombin G20210A Mutation, and/or a History of Provoked VTE (Part C) | Experimental | Not described Receives: Drug: CITY-FXI |
| In Adults with FVL, Prothrombin G20210A Mutation, and/or a History of Provoked VTE (Part C) | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence, severity, and relationship of treatment-emergent adverse events (TEAEs)
To evaluate the safety and tolerability of a single dose of CITY-FXI in healthy adults and adults with Factor V Leiden (FVL) or prothrombin G20210A mutation, and of a multiple dose regimen of CITY-FXI in adults with FVL or prothrombin G20210A mutation and/or a history of provoked VTE
Measured: Through study completion, up to Day 360
Secondary outcomes (6)
Maximum plasma concentration (Cmax)
To characterize the pharmacokinetics (PK) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation, and of a multiple dose regimen of CITY-FXI in adults with FVL or prothrombin G20210A mutation and/or a history of provoked VTE
Measured: Day 1 to Day 3 (Parts A and B); Days 1, 2, 91, 92 (Part C)
Area under plasma concentration time curve (AUC) of CITY-FXI
To characterize the pharmacokinetics (PK) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation, and of a multiple dose regimen of CITY-FXI in adults with FVL or prothrombin G20210A mutation and/or a history of provoked VTE
Measured: Day 1 to Day 3 (Parts A and B); Days 1, 2, 91, 92 (Part C)
Amount excreted in urine (Ae) of CITY-FXI
To characterize the pharmacokinetics (PK) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation
Measured: Day 1 to Day 3 (Parts A and B)
Change from baseline in levels of plasma Factor XI (FXI)
To characterize the pharmacodynamics (PD) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation, and of a multiple dose regimen of CITY-FXI in adults with FVL or prothrombin G20210A mutation and/or a history of provoked VTE
Measured: Up to Day 360
Change from baseline of Factor XI (FXI) activity
To characterize the pharmacodynamics (PD) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation, and of a multiple dose regimen of CITY-FXI in adults with FVL or prothrombin G20210A mutation and/or a history of provoked VTE
Measured: Up to Day 360
Change from baseline in activated partial thromboplastin time (aPTT)
To characterize the pharmacodynamics (PD) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation, and of a multiple dose regimen of CITY-FXI in adults with FVL or prothrombin G20210A mutation and/or a history of provoked VTE
Measured: Up to Day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2026
- Study start22 Jan 2026
- Primary completionMar 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Factor V LeidenStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 182 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, City Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07430397
- Sponsor's protocol ID
- FXI-1101
- Other IDs
- C24027
- Status last verified
- Sep 2026
- First submitted
- 9 Jan 2026
- Last updated
- 25 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No