In short
RNACS24757 is an investigational RNA-based therapy being studied for lung and liver disease caused by severe alpha-1 antitrypsin deficiency (AATD) in adults with the PiZZ genotype. A single authorised Phase 1/2 trial (NCT07227207) is evaluating its safety, tolerability, and efficacy in 60 participants. The study uses an open-label, dose-escalation design and measures whether the treatment raises functional alpha-1 antitrypsin levels in the blood.
Key points
- RNACS24757 is an investigational RNA therapy for alpha-1 antitrypsin deficiency (AATD).
- The trial is Phase 1/2, open-label, and multi-centre.
- It enrols 60 adults with the PiZZ genotype and lung and/or liver disease.
- The study evaluates safety, tolerability, and efficacy of single and repeat intravenous doses.
- A key goal is to raise functional alpha-1 antitrypsin levels in the blood.
- The trial is currently authorised but not yet recruiting.
What is RNACS24757?
RNACS24757 is an investigational RNA-based therapy. It is being developed for adults with severe alpha-1 antitrypsin deficiency (AATD) who have the PiZZ genotype and lung and/or liver disease. The substance is not yet authorised as a medicine; it is currently being studied in a Phase 1/2 clinical trial.
The full development code for the substance is TSRA-196, which is the name used in the trial registry. RNACS24757 is the short label used to refer to the same investigational substance.
How does RNACS24757 work?
The trial record indicates that RNACS24757 is an RNA-based therapy, which means it is designed to work at the level of genetic instructions inside cells. In alpha-1 antitrypsin deficiency, the body produces a faulty version of the alpha-1 antitrypsin protein, which can build up in the liver and fail to protect the lungs. The study measures whether treatment with RNACS24757 changes the amount of functional alpha-1 antitrypsin in the blood, using an elastase inhibition assay.
The exact molecular target of RNACS24757 is not described in the available registry data. The trial is designed to evaluate whether the treatment can raise total and functional alpha-1 antitrypsin levels above the lower limit of normal (LLN).
Which conditions is RNACS24757 studied for?
- Lung disease associated with alpha-1 antitrypsin deficiency (AATD) — a condition where low levels of functional alpha-1 antitrypsin leave the lungs vulnerable to damage, potentially leading to emphysema.
- Liver disease associated with alpha-1 antitrypsin deficiency (AATD) — a condition where the faulty alpha-1 antitrypsin protein accumulates in liver cells, which can cause inflammation, scarring, and eventually cirrhosis.
Both conditions are studied together in the same trial, in adults with the PiZZ genotype, which is the most common severe form of AATD.
How is RNACS24757 given?
RNACS24757 is given by intravenous use, meaning it is administered directly into a vein. The trial registry lists the intervention as "TSRA-196 (INTRAVENOUS USE)". No pharmaceutical form, such as a solution or powder for infusion, is specified in the available data.
What do the clinical trials show?
One clinical trial of RNACS24757 is registered: a Phase 1/2, open-label, multi-centre study in adults with the PiZZ genotype who have lung and/or liver disease associated with severe AATD. The trial aims to enrol 60 participants and is currently authorised, meaning it has received regulatory approval but is not yet recruiting.
The study is divided into three parts. Part 1 evaluates the safety and tolerability of a single dose of RNACS24757. Part 2 evaluates the efficacy of a single dose. Part 3 evaluates the efficacy of a second dose in adult participants with AATD.
The primary outcomes measured include the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in Part 1, and the proportion of participants whose serum levels of total alpha-1 antitrypsin reach or exceed the lower limit of normal (LLN) at Month 3 and Month 6 after treatment in Parts 2 and 3. The trial also measures the change from baseline in functional alpha-1 antitrypsin concentrations, determined using an elastase inhibition assay, up to Month 12.
The study is open-label, meaning both participants and researchers know which treatment is being given. It uses a dose escalation design in Part 1, followed by dose expansion in Parts 2 and 3.
What side effects are known?
No side effect data for RNACS24757 is available in the trial registry record or in any supplementary source provided. The trial is designed to evaluate safety and tolerability, including the incidence of treatment-emergent adverse events and serious adverse events, but results have not yet been reported.