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Clinical Trial to Evaluate the Efficacy and Safety of Dirocaftor/Posenacaftor/Nesolicaftor in Adults With CF

NCT06468527 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 41

Last updated 2025-11-24

No results posted yet for this study

Summary

CF is caused by mutations in the gene that encodes the 'Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)' channel. To re-establish the function of this complex chloride channel, typically two to three drug modes of action are needed. To date, clinical studies of CFTR modulators have focused on patients carrying the F508del CFTR mutation, which is present in approximately 80% of CF patients, or gating mutations which are present in 5% of CF patients (gating mutations result in a reduced opening of the CFTR-channel at the cell surface which limits the flow of chloride ions through the CFTR channel). Although CF is a monogenetic disease, the 15% remaining patients represent more than 2000 different rare and mostly uncharacterized CFTR mutations. Multiple pharma companies have one or more CF drugs in their developmental pipeline. However, it is not known which patients may respond to the drugs in the pipeline. It is hypothesized that by using individual patient's intestinal organoids to screen for drug response, a subset of patients with rare CFTR mutations can be identified who will clinically respond to drugs in the developmental pipeline. The Human Individualized Therapy of CF (HIT-CF) project has been designed to further evaluate this hypothesis. The project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 755021. The core of the project consists of a two-step approach to identify patients outside the existing drug label who may also benefit from CFTR-modulator treatment. In the first step of the project (HIT-CF Organoid Study, NTR7520), novel CFTR modulators and their combinations were tested on organoids from over 500 European and Israeli CF patients with rare CFTR mutations to identify patients who are predicted to clinically benefit from these treatments. The second step will evaluate the predicted clinical effect of the CFTR modulators in subjects identified by their organoid response to investigational products. CFTR modulators from the HIT-CF participating pharmaceutical company, FAIR Therapeutics, will be evaluated in the CHOICES clinical study described in this protocol. Data from this clinical study will be compared with the HIT-CF Organoid Study results to validate the organoid model.

Conditions

Interventions

DRUG

Diponecaftor

Diponecaftor is a triple combination of DIR/POS/NES. The combination therapy will be administered orally during 8 weeks. The daily dose contains: * DIR 300 mg/day * POS 600 mg/day * NES 10 mg/day

DRUG

Placebo

Placebo once daily for 8 weeks. Oral administration.

Sponsors & Collaborators

Principal Investigators

  • C.K. van der Ent · UMC Utrecht

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
CROSSOVER

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2024-06-03
Primary Completion
2025-06-26
Completion
2025-06-26

Countries

  • Belgium
  • France
  • Germany
  • Italy
  • Netherlands
  • Portugal
  • Spain
  • Sweden
  • United Kingdom

Study Locations

More Related Trials

Entities

Drugs
Diseases
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06468527 on ClinicalTrials.gov