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NCT Number: NCT07430397

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

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).

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Key information

Conditions

Factor V Leiden Cardiovascular Diseases Embolism and Thrombosis Prothrombin G20210A Thromboembolism Vascular Diseases Venous Thromboembolism Venous Thromboembolism (VTE)

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Richmond Pharmacology

London, SE1 1YR, United Kingdom

Location status: Recruiting

About this study

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)

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

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 (e.g., FVL with prothrombin G20210A mutation) (Parts B and C only)

Treatment and study plan

CITY-FXI

Drug

siRNA (subcutaneous injection)

Placebo

Drug

Saline (subcutaneous injection)

Primary outcomes

  1. Incidence, severity, and relationship of treatment-emergent adverse events (TEAEs)

    Time frame: Through study completion, up to Day 360

    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

Secondary outcomes

  1. Maximum plasma concentration (Cmax)

    Time frame: Day 1 to Day 3 (Parts A and B); Days 1, 2, 91, 92 (Part C)

    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

  2. Area under plasma concentration time curve (AUC) of CITY-FXI

    Time frame: Day 1 to Day 3 (Parts A and B); Days 1, 2, 91, 92 (Part C)

    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

  3. Amount excreted in urine (Ae) of CITY-FXI

    Time frame: Day 1 to Day 3 (Parts A and B)

    To characterize the pharmacokinetics (PK) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation

  4. Change from baseline in levels of plasma Factor XI (FXI)

    Time frame: Up to Day 360

    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

  5. Change from baseline of Factor XI (FXI) activity

    Time frame: Up to Day 360

    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

  6. Change from baseline in activated partial thromboplastin time (aPTT)

    Time frame: Up to Day 360

    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

Interested in participating?

Recruiting

Interested in participating?

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Sponsors and collaborators

Lead sponsor

City Therapeutics

Industry

Registry information

Official study 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

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Feb 24, 2026
Registry last updated
Sep 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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