Frequently Asked Questions (FAQs)

Clinical studies (or trials) are a type of research performed to learn about the effects of investigational new drugs or treatments. The studies follow predetermined procedures, called the clinical study protocol. Clinical studies are the most important way for researchers to better understand whether a new drug or treatment is safe and effective for a particular condition.

ARCT-032 (study treatment) is an inhaled messenger RNA (mRNA) encased in tiny fat particles, i.e., a lipid-mediated delivery system called LUNAR®. ARCT-032 is delivered by a special nebulizer directly to the lungs to target a normal copy of CFTR mRNA directly to lung cells that lack a functional copy. These cells then use the newly delivered instructions provided by the mRNA to create functional CFTR and restore a proper salt and water balance in the airways.

To learn more about mRNA therapy in CF, please visit the Cystic Fibrosis Foundations website.

Messenger RNA (mRNA) is a natural molecule that takes the ‘code’ from our genes and forms a template that can be translated into essential proteins by our cells, much like a chef translates a recipe into a delicious dish. The most well-recognized use of mRNA technology has been in vaccines, such as COVID-19 vaccines; however, applications of mRNA extend to other disease areas. In vaccines (used for disease prevention), the mRNA carries the instructions for a viral component that triggers the body to produce a protective immune response. By contrast, in medicines that treat disease, the mRNA carries the instructions for a missing or defective protein and enables its production.

Gene therapy has the potential to treat diseases at their root causes by correcting or replacing defective genetic material (DNA). A virus carrier or vector delivers the gene to the targeted cells of the body. Once inside the cell nucleus (the “control center”), gene therapy works to correct or replace the genetic material that is not properly working. This is done by gene editing or gene addition. Under ideal circumstances, the beneficial changes made to the genetic material are permanent, resulting in a long-lasting cure; however, if the therapy misses its intended target, side effects can also be long-lasting. By contrast, mRNA therapy does not enter the cell nucleus, nor does it change the genetic material. mRNA therapy only instructs cells how to assemble key ingredients to create compounds using the cell’s own internal “assembly line.” Its effects are temporary and after the compound is made, the mRNA therapy gets broken down. Repeated dosing is necessary to maintain the beneficial effects, but, if side effects occur, the therapy can be stopped to allow them to resolve.

Yes, all study participants will receive ARCT-032 by inhalation with a nebulizer designed specifically for ARCT-032. There is no placebo group in this study.

Our LUNAR®-CF program used many steps to optimize ARCT-032 as a potential therapy for CF. LUNAR® formulations are compatible with nebulization and stable in the presence of CF sputum. Our studies have demonstrated that LUNAR® efficiently delivers mRNA to airway cells across several animal species, and that ARCT-032 generates CFTR, which is functionally active in restoring chloride activity in cells from CF donors and in CF animal models. Animal studies were also performed to guide the range of ARCT-032 doses that can be safely given in clinical trials. Importantly, a preliminary study showed that single doses of ARCT-032 given to healthy adults and 2 doses given to people with CF were generally tolerated and safe.

Yes, the therapy is designed to correct the underlying cause of CF, regardless of the CFTR mutation type. Some mutations produce poorly functioning CFTR and other mutations produce no CFTR at all. ARCT-032 is an mRNA replacement therapy that delivers a normal copy of the CFTR mRNA to airway cells, no matter which type of mutation the person carries. The LUNAR® formulation (tiny fat particles that coat the mRNA) enables the mRNA to enter the airway cells and produce a fully functional CFTR. LunairCF is enrolling adults with CF who either carry Class 1 mutations for which CFTR modulators aren't effective, or those who are eligible to take modulators but do not take them because of side effects, poor response, or poor access to modulators.

There is no cost to participate in these clinical studies. Travel expenses will be covered, and there is a stipend (where allowed by law) to help compensate for time, lost work hours, and other considerations.

Clinical study participation is an important decision. Below are some helpful questions to ask when speaking to your physician or family members to determine whether participation is right for you:

• What type of treatment is being studied?
• What tests or procedures will be done if I participate?
• What type of travel support is provided in this study?
• How will this treatment impact my current treatment regimen?
• What risks and benefits can I expect if I participate in this study?

To learn more about mRNA therapy and CF, please visit the the Cystic Fibrosis Foundation website. Additional information is also available on the Cystic Fibrosis Foundation’s Clinical Trial site: Study of ARCT-032 in adults with CF who are not on CFTR modulator therapy (Arcturus ARCT-032-02).