Results of innovative new trial for people with rare CF variants shows promise

The CHOICES clinical trial is the second part of a European CF research study called HIT-CF. HIT-CF was developed to investigate whether people with CF with rare CF variants might benefit from CFTR modulators. 

Why was the HIT-CF study needed?

Every person with CF has two disease-causing variants, one inherited from each parent. Around the world, there are more than 1,000 different CF-causing variants in the CFTR gene. Some variants are more common than others. 

While approximately 90% of people with CF in the UK (around 10,000 people) have at least one copy of the ‘F508Del’ CF variant, the number of people with rarer CF variants is much smaller. For example, for some variants there are less than five people in the UK with the same one.

The small numbers of people with rare CF variants means a conventional clinical trial would be unable to collect enough data to prove the benefits, and this is where the design of the HIT-CF study came in.

Selecting participants based on lab results

The first part of HIT-CF was to invite 500 people with CF with rare CF variants from 16 countries across Europe to donate tissue for a lab test of the new medicines. This included participants from the UK. Each person agreed to have a rectal biopsy, where a small tissue sample from the bowel wall  was removed. The samples were used to create ‘mini guts’ also known as ‘organoids’ in the lab.

Organoids swell when the CF protein is working. Researchers added the new modulator therapies to the organoids created from each participant’s biopsy sample. If the organoids swelled, it showed that the new modulator therapy improved the function of their CF protein and may also be beneficial if given as a medicine to that individual. People whose organoids responded to the medicines became known as ‘responders’. Responders in the HIT-CF study were invited to take part in the CHOICES clinical trial. 

What did the study find?

The CHOICES study found that people whose organoids responded to the new CFTR modulators in the lab, also saw a beneficial effect when they took the medicines in the clinical trial.

In these early studies, the new combination of CFTR modulators, owned by Fair Therapeutics, were found to be safe and beneficial to people who took part in the study.

What do these results mean for me?

These results can be used as evidence for the medicine regulators who approve the use of medicines and access to them. The results show that testing medicines in individuals with CF in the lab, prior to running clinical trials, is an effective way to screen possible benefits of new medicines.

These results particularly offer hope to people with rare CF variants, who may not be able to take part in clinical trials of new medicines due to lack of information about their variants.

The HIT-CF study was funded by the European Union. These results were announced as part of the final report to the funders. Further clinical trials are needed before FAIR Therapeutics can apply for these medicines to be licensed. 

The medicines tested in the CHOICES study can progress to next phase of development, which is another step closer to them being used in clinic.

Where can I find out more?

You can read the press release about the results of the CHOICES clinical trial on CF Europe’s website. The HIT-CF website also has lots of information about different stages of the trial as it progressed.

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