In short
RNAIVT9315 is an investigational RNA-based therapy being studied for alpha-1 antitrypsin deficiency (AATD), a genetic condition that can cause lung and liver disease. One authorised clinical trial, NCT07227207, is evaluating this substance in 60 adults with the PiZZ genotype who have lung and/or liver disease associated with severe AATD. The trial is a Phase 1/2, open-label, multi-center study investigating safety, tolerability, and efficacy of the therapy.
Key points
- RNAIVT9315 is an investigational RNA therapy for alpha-1 antitrypsin deficiency (AATD).
- The Phase 1/2 trial is authorised and plans to enroll 60 adults with the PiZZ genotype.
- The study targets people with lung and/or liver disease associated with severe AATD.
- The trial evaluates safety, tolerability, and efficacy of single and repeat doses.
- Treatment is given by intravenous use in an open-label, multi-center design.
- The primary outcome measures include serum levels of total AAT at Month 3 and Month 6.
What is RNAIVT9315?
RNAIVT9315 is an investigational RNA-based therapy. It is not yet an authorised medicine. The substance is being developed for the treatment of alpha-1 antitrypsin deficiency (AATD), a genetic condition caused by mutations in the SERPINA1 gene. People with the PiZZ genotype have very low levels of the alpha-1 antitrypsin (AAT) protein, which normally protects the lungs and liver from damage.
The trial record for NCT07227207 lists the intervention as TSRA-196, which is the development code for RNAIVT9315. No trade name has been assigned, as the substance is still in clinical development.
How does RNAIVT9315 work?
The trial record does not provide a detailed mechanism of action for RNAIVT9315. The study aims to evaluate whether the therapy can increase serum levels of total AAT and functional AAT in participants with severe AATD. Functional AAT is measured using an elastase inhibition assay, which tests the ability of the protein to block the enzyme elastase that can damage lung tissue.
The primary outcomes include the proportion of participants who achieve serum levels of total AAT at or above the lower limit of normal (LLN) at Month 3 and Month 6 after treatment. This suggests the therapy is intended to restore AAT levels in the blood.
Which conditions is RNAIVT9315 studied for?
- Lung disease associated with AATD — people with AATD can develop emphysema and other lung problems because the lungs lack protection from the enzyme elastase.
- Liver disease associated with AATD — the abnormal AAT protein can accumulate in liver cells and cause damage, leading to conditions such as cirrhosis.
- Severe alpha-1 antitrypsin deficiency with the PiZZ genotype — the trial specifically includes adults with this genotype, which is associated with the most severe forms of AATD.
How is RNAIVT9315 given?
RNAIVT9315 is given by intravenous use, meaning it is administered directly into a vein. The trial record lists the intervention as a drug for intravenous use. No information about the pharmaceutical form, such as a solution or powder for infusion, is provided in the registry data.
The study includes a dose escalation part, a dose expansion part, and a single repeat dose part. This means the trial will first test different doses to find a suitable one, then expand to more participants, and also evaluate a second dose in some participants.
What do the clinical trials show?
One clinical trial, NCT07227207, is authorised and listed in the registry. It is a Phase 1/2, open-label, multi-center study with a planned enrollment of 60 participants. The trial is divided into three parts. Part 1 evaluates the safety and tolerability of a single dose. Part 2 evaluates the efficacy of a single dose. Part 3 evaluates the efficacy of a second dose.
The primary outcome measures differ by part. In Part 1, the main measure is the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). In Parts 2 and 3, the primary measures are the proportion of participants with serum levels of total AAT at or above the lower limit of normal at Month 3 and Month 6 after treatment, and the change from baseline in functional AAT concentrations to Month 12.
The trial is open-label, meaning both participants and researchers know which treatment is being given. It is conducted at multiple centers. The status is authorised, meaning the trial has received approval to proceed but may not yet be recruiting participants.
No results from this trial have been published in the registry data. The study is still in its early stages, and findings will become available as the trial progresses.
What side effects are known?
The trial record does not list any side effects for RNAIVT9315. As the trial is still in its early phases and no results have been reported, the safety profile of this investigational therapy is not yet known. The study is designed to collect information on treatment-emergent adverse events and serious adverse events, which will provide safety data once the trial is completed.