Gut Imaging for Function & Transit in Cystic Fibrosis Study 2

NCT04006873 | Completed Phase 2 FDA Drug

• 1 other identifier: 18RM039
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

People with Cystic Fibrosis (CF) have problems digesting their food properly. More than 8 in 10 people with CF must take medication to assist their digestion. In spite of this, complications such as bowel blockage occur. Finding out how already licenced drugs for CF work in the gut is the first step in repurposing medications. Tezacaftor/Ivacaftor with Ivacaftor is a drug combination which corrects the basic defect in CF an has shown improvements on lung function. The purpose of this study is to evaluate, using Magnetic Resonance Imaging (MRI) and patient-reported outcomes, whether Tezacaftor/Ivacaftor with Ivacaftor has an effect on improving gastrointestinal problems in CF.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Oro-caecal Transit Time

  Time taken after eating for ingested food to be identifiable at the caecum on MRI

  1 day of scanning

Secondary Outcomes (4)

• Gastric volume

  1 day of scanning

• Small bowel water content (corrected for body surface area)

  1 day of scanning

• Colonic volume (corrected for body surface area)

  1 day of scanning

• Gastrointestinal symptoms

  1 day of scanning

Other Outcomes (7)

• Sigmoid colon volume

  1 day of scanning

• T1 relaxation of ascending colon chyme

  1 day of scanning

• Fat fraction of ascending colon chyme

  1 day of scanning

Study Arms (2)

Tezacaftor/Ivacaftor in combination with Ivacaftor

ACTIVE COMPARATOR

A film-coated tablet containing 100mg tezacaftor and 150mg ivacaftor will be taken in the morning. A film-coated tablet containing 150mg ivacaftor will be taken in the evening. Participants will take these tablets for 28 days. All tablets are licensed for use in the EU.

Drug: Tezacaftor/Ivacaftor + Ivacaftor

Placebo

PLACEBO COMPARATOR

A visually matched placebo to the active drugs will be taken in the morning and in the evening for 28 days.

Drug: Placebo oral tablet

Interventions

Tezacaftor/Ivacaftor + Ivacaftor DRUG

As per description in arms.

Also known as: VX-661 100mg / VX-770 150mg active tablets, VX-770 150mg active tablets

Tezacaftor/Ivacaftor in combination with Ivacaftor

Placebo oral tablet DRUG

As per description in arms

Also known as: Matching placebo tablets

Placebo

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• capacity to consent, or to understand the requirements of the study where parental consent is needed
• confirmed diagnosis of CF, either by sweat test or genetic testing. Tezacaftor/Ivacaftor is indicated only for patients homozygous for the commonest CF mutation - p.Phe508del and so we will enrol only CF patients with this genotype

You may not qualify if:

• currently taking CFTR modulator drug
• Contra-indication to use of Tezacaftor/Ivacaftor
• Measurement of FEV1 \<40% predicted using Global Lung Initiative criteria, according to clinical records, as participants will be required to perform a series of 10 second breathholds throughout MRI scanning
• Contra-indication to MRI scanning, such as embedded metal, pacemaker.
• Pregnancy
• Unable to stop medications directly prescribed to alter bowel habit, such as laxatives or anti-diarrhoeals, on the study day
• Previous resection of any part of the gastrointestinal tract apart from appendicectomy or cholecystectomy. Surgical relief of meconium ileus or DIOS will be permitted unless clinical records show excision of intestine \>20cm in length.
• Intestinal stoma
• Diagnosis of inflammatory bowel disease or coeliac disease confirmed by biopsy
• Gastrointestinal malignancy
• Unable to comply with dietary restrictions required for the study.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead
• Vertex Pharmaceuticals Incorporated: collaborator
• Cystic Fibrosis Foundation: collaborator
• Cystic Fibrosis Trust: collaborator
• University of Nottingham: collaborator
• Nottingham University Hospitals Charity: collaborator

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Related Publications (1)

• Ng C, Dellschaft NS, Hoad C, Marciani L, Spiller R, Crooks C, Hill T, Menys A, Mainz JG, Barr H, Gowland PA, Major G, Smyth AR. A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study. NIHR Open Res. 2024 Mar 19;3:65. doi: 10.3310/nihropenres.13510.2. eCollection 2023.

  PMID: 39139270 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

tezacaftor, ivacaftor drug combination; tezacaftor; ivacaftor; Exercise

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Alan Smyth, Prof

  University of Nottingham

  PRINCIPAL INVESTIGATOR

• Giles Major, Dr

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 5, 2019
• Study Start: September 3, 2019
• Primary Completion: October 29, 2020
• Study Completion: October 29, 2020
• Last Updated: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)