FAQs on genetic therapy clinical trials

Eligibility criteria  will vary from trial to trial. Some genetic therapy trials will target or prioritise people who are currently unable to benefit from CFTR modulators such as Kaftrio. Certain genetic therapy treatments may be specifically designed for people with certain CF variants whereas other treatments may be investigated across a range of CF variants.

For safety reasons, certain things may be listed as exclusion criteria for a genetic therapy trial (eg people who have received a transplant), but the exclusion criteria will vary from trial to trial. It is also common for the first trials of a new treatment to look at the safety and effectiveness in adults, and then later trials will look at the treatment in younger age groups. Our CF LIVE video Q&A discusses this at around 39 minutes.

You will be able to find eligibility criteria for each trial via our Trials Tracker.

Each trial will have their own upper and lower limits for lung function (percent predicted FEV1) of trial participants, so this might vary. Quite often, the lower limit is around 40% FEV1 and the upper limit can be around 90% FEV1. These limits are in place to reduce any safety risks whilst also maximizing the chance of being able to see any positive outcomes from the treatment being investigated. Once the treatment has first been investigated in this group of patients, in future the treatment may be investigated at lower (and higher) lung function thresholds.

Watch an explanation about lung function and genetic therapy trials

The two main ways genetic therapy treatment might be given to people with CF is either as a nebulised (inhaled) or intravenous (injected into the bloodstream) treatment. 

The clinical trials we’re likely to see over the next few years would be targeting the lung. The most common method for these treatments will be via a nebuliser. We are not likely to see clinical trials for genetic therapy treatments that target other areas or the whole body for many years. Our CF LIVE video Q&A discusses this at around 37 minutes.

This will depend on the specific trial, the stage (or phase) of the trial and how far into the trial you are. Early phase (phase 1 or 2) trials are the first trials investigating the treatment in humans and will have a large focus on evaluating the safety and dosage of the treatment. During these trials, when you first receive the treatment you may be required to stay for a few nights in the hospital so you can be carefully monitored if there are any side effects.

You may also be asked to visit the hospital a few times after the treatment to check your overall health (or to receive repeat doses). Later in the trial, the visit frequency may become less, and follow-up appointments may be as little as once per year or linked with your usual annual review. The number of hospital visits and overnight stays will vary from trial to trial, so do speak with your clinical team if you have any concerns or want to find out more about a particular trial.

Early genetic therapy trials will be run in a select number of centres which have special capabilities for running these more complicated studies. Through the Clinical Trials Accelerator Platform (CTAP), we have created a network of dedicated early phase centres across England, Wales, Scotland and Northern Ireland who will be able to run the first genetic therapy trials. These early phase centres will work with other CF centres across the UK to make sure all people with CF are offered the opportunity to travel to their nearest early phase centre to take part.

No. Everyone will have equal and fair opportunity to express interest and participate in a genetic therapy trial, regardless of where you live and where you receive your usual CF care. For people who are not registered to one of the centres running the trial, your clinical team will put you in touch with the nearest or most convenient trial centre for you. Our CF LIVE video Q&A discusses this at around 42 minutes. 

All research and new treatments carry with them some risk, and this is no different for genetic therapies. The most notable risks associated with genetic therapy treatments would be those arising from the delivery method and how the genetic therapy works.

Some genetic therapies use a virus to deliver the treatment. Clinical trials of these therapies would evaluate any inflammation or immune response to the virus, and make sure the correct cells are targeted by the treatment.

Some gene therapy treatments are designed to be inserted into the DNA of the cell, known as ‘integrating gene therapies’. For these therapies it is important to find out where in the DNA the therapy is inserted, and whether its location causes unwanted side effects. 

Because of the nature of these risks, researchers and regulators want to make absolutely sure that the treatment is safe even after a long period of time.

Some viral vectors may carry an increased risk of being recognized by the body as ‘foreign’ and triggering an immune response. However, this will vary between different viral vectors. Before coming to a clinical trial in humans, all genetic therapy treatments are thoroughly investigated in pre-clinical research work, to evaluate among other things, the likelihood of triggering a significant immune response and causing inflammation. For some genetic therapy treatments, you may experience cold-like symptoms for a few days after taking the medication, but you will be monitored very carefully across all aspects of your health while you are on the trial.

While you are taking the treatment during the trial, your health will be carefully and thoroughly monitored. This is likely to include checking numerous safety signals via blood tests and vital signs (eg your pulse rate, body temperature, breathing rate and blood pressure). The team will monitor your lung health and the health of your other organs, as well as checking for any acute inflammation or other infection-like symptoms in response to the treatment. You may initially be monitored very frequently over several days, potentially with an overnight hospital stay when you start the treatment. A long follow-up period may occur after the trial, to look at the long-term effects of the treatment both in terms of lung health and any wider health outcomes.

This will depend on the type of genetic therapy treatment you receive. Some genetic therapy treatments, like gene therapy or RNA therapy, act as replacements for the faulty CFTR gene and protein. This means that they do not remove the existing copy of the faulty gene, and faulty CFTR protein may still be produced by the cell, but corrected versions of the CFTR protein will also be produced. Other genetic therapy treatments like gene editing aim to repair the existing CFTR genetic sequence to create a corrected version.

Some genetic therapy trials may exclude people who have recently participated in a different genetic therapy trial, because it might be difficult to evaluate if any outcomes are a result of the new treatment or the previous one. Some of the first genetic therapy trials may have a follow-up period of several years to evaluate long-term effects and safety. Do speak with your clinical team if you have any concerns about participating in future genetic therapy studies and to work out what trials may be best for you. The Trust will be working with the trial companies and other relevant governing bodies to ensure fair and reasonable opportunities are given to the CF community to participate in future trials if one genetic therapy treatment doesn’t work for them.

Taking part in a genetic therapy trial, or withdrawing from the trial, will not affect the usual CF care or treatments you receive.

Some genetic therapy trials may have a follow-up period of several years after you complete the trial. This is to allow the researchers to thoroughly evaluate the long-term safety and effects of the treatment. It is important to make sure that in the long-term the treatment doesn’t lead to any unintended outcomes.

This will vary between trials, but it is likely that the long follow-up period will involve a thorough check-up once per year, a bit like your usual CF annual review. Some of this follow-up data may be able to be collected via the UK CF Registry or as part of your normal clinic visits and therefore can likely be done at your local centre. Chat to your clinical team if you’re unsure about the follow-up requirements for a specific trial.

Some trials may have an open-label extension study after the trial, while the original trial results are being evaluated and before the treatment is licensed for wider clinical use. This allows participants to continue to access the treatment, and the tolerability of the treatment is assessed over a longer period of time.

In the UK, applications may also be able to be made via the early access to medicines scheme (EAMS) to enable continued patient access to a promising new treatment before it is licensed. Talk to your clinical and research teams to discuss what options might be available for continuing treatment after the trial.

Speak to your clinical team, reach out to one of our early phase CF trial coordinators or contact us at [email protected] if you have any questions about upcoming genetic therapy trials.

You may also find it useful to read our general information about taking part in clinical trials