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

NCT07430397 | Recruiting Phase 1

• 2 other identifiers: FXI-1101C24027
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 1

Brief 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, and adults with a history of provoked venous thromboembolism (VTE).

Conditions

Factor V Leiden; Prothrombin G20210A; Venous Thromboembolism (VTE)

Keywords

Factor XI; siRNA

Outcome Measures

Primary Outcomes (1)

• 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

  Through study completion, up to Day 360

Secondary Outcomes (6)

• Maximum plasma concentration (Cmax)

  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

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

• Amount excreted in urine (Ae) of CITY-FXI

  Day 1 to Day 3 (Parts A and B)

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

  Up to Day 360

• Change from baseline of Factor XI (FXI) activity

  Up to Day 360

Study Arms (6)

CITY-FXI in Healthy Adults (Part A)

EXPERIMENTAL

Drug: CITY-FXI

In Healthy Adults (Part A)

PLACEBO COMPARATOR

Drug: Placebo

CITY-FXI in Adults with Factor V Leiden or Prothrombin G20210A Mutation (Part B)

EXPERIMENTAL

Drug: CITY-FXI

In Adults with Factor V Leiden or Prothrombin G20210A Mutation (Part B)

PLACEBO COMPARATOR

Drug: Placebo

CITY-FXI in Adults with FVL, Prothrombin G20210A Mutation, and/or a History of Provoked VTE (Part C)

EXPERIMENTAL

Drug: CITY-FXI

In Adults with FVL, Prothrombin G20210A Mutation, and/or a History of Provoked VTE (Part C)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

CITY-FXI DRUG

siRNA (subcutaneous injection)

CITY-FXI in Adults with FVL, Prothrombin G20210A Mutation, and/or a History of Provoked VTE (Part C); CITY-FXI in Adults with Factor V Leiden or Prothrombin G20210A Mutation (Part B); CITY-FXI in Healthy Adults (Part A)

Placebo DRUG

Saline (subcutaneous injection)

In Adults with FVL, Prothrombin G20210A Mutation, and/or a History of Provoked VTE (Part C); In Adults with Factor V Leiden or Prothrombin G20210A Mutation (Part B); In Healthy Adults (Part A)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• City Therapeutics: lead

Study Sites (1)

Richmond Pharmacology

London, SE1 1YR, United Kingdom

RECRUITING

MeSH Terms

Conditions

Venous Thromboembolism

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Medical Director

  City Therapeutics

  STUDY DIRECTOR

Central Study Contacts

City Therapeutics

CONTACT

857-219-5440; clinicaltrials@citytx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2026
• First Posted: February 24, 2026
• Study Start: January 22, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: September 25, 2026

Record last verified: 2026-09

Locations

GB (1)