HIT-CF Organoid Study

Details

Therapeutic category
Restore CFTR Function
Trial status
Closed - follow up complete Participating Centres
Phase
Not Applicable

Full title

Part 1 HIT-CF Project: Stratifying Cystic Fibrosis Patients Based on Intestinal Organoid Response To Different CFTR-modulators

Cystic fibrosis (CF) is the most common inherited life shortening condition in white populations, with over 10 000 people in the UK with the disease. It is caused by gene changes ('mutations') in the CF gene (termed CFTR or 'Cystic Fibrosis Transmembrane Conductance Regulator'). Over 2000 mutations in CFTR have been identified. New innovative and effective ‘mutation-specific’ drugs are available or in development for up to 90% of people with CF (ie. those with the most common 20-30 mutations). These are called ‘CFTR modulators.’ However, this leaves an important minority (~10%) of people with CF with no modulator in development as their mutations are very rare and only a small number of individuals have these specific mutations, making studying these patients in traditional trials very challenging. Therefore, the Human Individualized Treatment for CF (HIT-CF) project has been developed to address this unmet need, ie. to develop personalised treatments for this important group. HIT-CF is a Europe-wide, multi-centre project, which comprises two parts:

This IRAS submission relates to the first part - the organoid study - in which patients with rare CFTR mutations will be recruited and intestinal organoids produced from rectal biopsies from each patient will be generated. Intestinal organoids, sometimes called ‘mini-intestines,’ are cell cultures made from stem cells so they contain the same mutations as the person from whom the biopsies are derived. Using this laboratory model, candidate modulator drugs can then be tested to assess for responsiveness (thus potentially predicting response in real life). In the second part of HIT-CF - the clinical trial - these modulators will then be tested in patients identified from the organoid study as likely responders, thus increasing the likelihood of showing efficacy. We plan to test drugs on organoids derived from 500 patients across Europe.
Trial Reference Number
119685
Intervention
Rectal biopsy
Recruitment target
500
Last edited date
14/12/2020
CF sponsor
University Medical Centre Utrecht
CF sponsor type
Academic

Who can take part?

Top inclusion criteria
  • Male or female with confirmed diagnosis of CF
  • Adult age on the date of informed consent for biopsy taking
Top exclusion criteria
  • Subject has at least one of the following CFTR-mutations: F508del, G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, R117H, A455E, 3849+10kbC>T
  • Subject has a combination of any two of the following mutations: G542X, 1717-1G>A, 621+1G>T, 3120+1G>A, 1898+1G->A, CFTRdele2,3 and 2183AA->G

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