Factor V Leiden, Prothrombin G20210A
Conditions
Keywords
Factor XI, siRNA
Brief summary
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.
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
Interventions
DRUGCITY-FXI
siRNA (subcutaneous injection)
DRUGPlacebo
Saline (subcutaneous injection)
Sponsors
City Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, severity, and relationship of treatment-emergent adverse events (TEAEs) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) | Day -1 to Day 3 | To characterize the pharmacokinetics (PK) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation |
| Area under plasma concentration time curve (AUC) of CITY-FXI | Day -1 to Day 3 | To characterize the pharmacokinetics (PK) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation |
| Amount excreted in urine (Ae) of CITY-FXI | Day -1 to Day 3 | To characterize the pharmacokinetics (PK) of a single dose of CITY-FXI in healthy adults and adults with FVL or prothrombin G20210A mutation |
| Change from baseline in levels of plasma Factor XI (FXI) | 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 |
| Change from baseline of Factor XI (FXI) activity | 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 |
| Change from baseline in activated partial thromboplastin time (aPTT) | 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 |
Countries
United Kingdom
Contacts
CONTACTCity Therapeutics
Outcome results
None listed