CompletedPhase IIInterventional

Testing new medicine for adults with Cystic Fibrosis who do not have access to the currently available CFTR-modulating drugs due to genetic mutations

Cystic fibrosis is an inherited condition that causes thick, sticky mucus to build up in the lungs and digestive system. While newer medicines called CFTR modulators have transformed care for many, people with very rare gene mutations currently have no approved treatments available. The CHOICES study is testing a new triple-drug combination (dirocaftor, posenacaftor, and nesolicaftor) for adults with these rare mutations. Before joining, participants had tiny samples of their own tissue grown into 'mini-guts' in a laboratory to check if the medicine might work for their specific genetics. In this trial, adults aged 18 and older will take capsules once a day. Each person will receive the active medicine for eight weeks and a dummy pill (placebo) for eight weeks, in random order. Researchers will monitor lung function, sweat tests, and overall well-being across 10 hospital visits to see how well the treatment works.

At a glance

Status

Completed

Phase

Phase II

Sponsor

University Medical Center Utrecht

Enrolment target

Start

01 May 2024

Estimated completion

30 Nov 2024

Treatment of Cystic Fibrosis (CF) in patients with CFTR mutations who are responders in the organoid assay

What is this study about?

Cystic fibrosis (CF) is an inherited condition that affects how salt and water move in and out of cells. This leads to a build-up of thick, sticky mucus in the lungs, digestive tract, and other organs, causing breathing difficulties and repeated infections. In recent years, modern medicines called CFTR modulators have helped many people by fixing the faulty protein that causes CF. However, these medicines only work for people with specific, common gene changes, leaving people with rare mutations without targeted treatment options.

The CHOICES study aims to change this. Researchers previously took tiny tissue samples from patients to grow 'mini-guts' (organoids) in a laboratory. By testing experimental medicines on these living cell models, scientists could see whose cells responded positively. This study is now testing that same medicine in the people whose lab tests showed promising results.

The trial tests a combination of three new medicines: dirocaftor, posenacaftor, and nesolicaftor. Taken together as daily capsules, they work in harmony to help the faulty protein work more normally. This study is an important step forward in personalised medicine, offering hope for targeted treatments tailored to people with rare forms of cystic fibrosis.

Key takeaways

Tests a new triple combination medicine for adults with rare cystic fibrosis mutations.
Aimed at people who cannot access currently approved CFTR modulators.
Participants must have previously taken part in the HIT-CF 'mini-gut' lab test.
Everyone receives both the real medicine and a dummy pill for eight weeks each.
Involves 10 hospital visits over approximately five to six months.

Who may be eligible?

To take part, you must be 18 or older with a confirmed diagnosis of cystic fibrosis. You must have already completed the earlier HIT-CF organoid screening study, where laboratory tests on your tissue samples showed a positive response to the study drugs. Your general health should be stable, with lung function (FEV1) between 40% and 90%, and a body mass index (BMI) between 16 and 30.

This trial is specifically designed for people who cannot access current CFTR treatments. For this reason, you cannot take part if you carry common mutations (such as F508del) that already qualify you for standard NHS modulator therapies like Kaftrio.

You also need to be a non-smoker, agree to use reliable contraception if applicable, and be willing to attend regular hospital check-ups throughout the trial period.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 18 or older with confirmed cystic fibrosis.
I previously took part in the HIT-CF organoid screening study.
I do not carry common CF mutations (like F508del) that qualify for approved modulators.
My lung function (FEV1) is between 40% and 90%.
I am a non-smoker with a BMI between 16 and 30.

Answer every question to see your result.

What does participation involve?

Taking part lasts around five to six months and involves 10 clinic visits. The trial uses a 'crossover' design, meaning every participant gets to try both the real medicine and a dummy pill (placebo). For eight weeks, you will take the three-in-one medicine as daily capsules by mouth, and for another eight weeks, you will take the dummy pill. The order in which you receive them is chosen at random, and neither you nor your doctors will know which you are taking at the time.

During your hospital visits, the medical team will carry out health checks to see how you are doing. These include breathing tests to check your lung function, sweat tests, heart traces (ECGs), and blood and urine samples. You will also fill in questionnaires about your daily symptoms and quality of life. After completing both eight-week treatment periods, you will have a final follow-up visit to ensure you remain well.

Potential risks and benefits

A potential benefit is that the study medicine may improve your lung function and ease your cystic fibrosis symptoms, although this cannot be guaranteed. Taking part will also provide valuable scientific knowledge to help find treatments for others with rare mutations. The risks include possible side effects from the study medicines, which are still being evaluated. Study tests can also cause mild discomfort, such as slight pain or temporary bruising from blood samples. Taking part is entirely voluntary, and you are free to leave the trial at any time without it affecting your standard NHS care.

Locations (18)

Royal Brompton Hospital
Approximate
London, England
University Hospitals Birmingham NHS Foundation Trust
City only
Birmingham, England
University Hospital Southampton
City only
Southampton, England
UZ Leuven
Approximate
Leuven, Belgium
Motol University Hospital
City only
Prague, Czech Republic
Centre Hospitalier Universitaire De Nice
Unverified
Nice, France
Centre Hospitalier Universitaire De Toulouse
Unverified
Toulouse, France
Charite Universitatsmedizin Berlin KöR
Unverified
Berlin, Germany
Medizinische Hochschule Hannover
Unverified
Hannover, Germany
Azienda Ospedaliera Universitaria Integrata Verona
Unverified
Verona, Italy
Azienda Ospedaliera Universitaria Meyer IRCCS
Unverified
Florence, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Unverified
Milan, Italy

Common questions

What is an organoid test?

An organoid is a 'mini-gut' grown in a laboratory from a tiny sample of your own tissue. Scientists test experimental medicines on these cells first to see if they are likely to work in your body.

Will I definitely receive the active medicine?

Yes. Because this is a crossover trial, every participant receives the active medicine for eight weeks and the dummy pill (placebo) for eight weeks.

Can I take part if I already take an approved CFTR modulator?

No. This study is only for people with rare genetic mutations who do not qualify for currently available CFTR modulators.

How do I take the study treatment?

The medicines come as capsules that you swallow once a day at home.

What happens if I change my mind during the study?

You are free to stop taking part at any time. Leaving the trial will not affect your relationship with your healthcare team or your usual care.

How to find out more

K. van der Ent

K.vanderEnt@umcutrecht.nl +31 887553725 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.