A Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CITY-FXI in Healthy Adults and Adults With FV 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 is a first-in-human (FIH), single-center, randomised, double-blind, placebo-controlled, single ascending dose (SAD) study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CITY-FXI in healthy adults and adults with Factor V Leiden (FVL) or prothrombin G20210A mutation.

Study Overview

• Status: Recruiting
• Conditions: Prothrombin G20210A; Factor V Leiden
• Intervention / Treatment: Drug: CITY-FXI; Drug: Placebo

Detailed Description

The study will be conducted in two 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

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: City Therapeutics; Phone Number: 857-219-5440; Email: clinicaltrials@citytx.com

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Recruiting
    • Richmond Pharmacology
    • Contact: Dr. Ulrike Lorch; Phone Number: +44 0207 042 5800; Email: volunteer@richmondpharmacology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CITY-FXI in Healthy Adults (Part A)	Drug: CITY-FXI; siRNA (subcutaneous injection)
Placebo Comparator: In Healthy Adults (Part A)	Drug: Placebo; Saline (subcutaneous injection)
Experimental: CITY-FXI in Adults with Factor V Leiden or Prothrombin G20210A Mutation (Part B)	Drug: CITY-FXI; siRNA (subcutaneous injection)
Placebo Comparator: In Adults with Factor V Leiden or Prothrombin G20210A Mutation (Part B)	Drug: Placebo; Saline (subcutaneous injection)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Through study completion, up to Day 360

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day -1 to Day 3
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	Day -1 to Day 3
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	Day -1 to Day 3
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	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	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	Up to Day 360

Collaborators and Investigators

• Sponsor: City Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: January 9, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: siRNA; Factor XI
• Other Study ID Numbers: FXI-1101; C24027 (Other Identifier: Richmond Pharmacology)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No