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

Phase 1RecruitingNCT07430397

City Therapeutics128 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

128

Conditions

Factor V Leiden Prothrombin G20210A

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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

Time frame: Through study completion, up to Day 360

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Up to Day 360

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts