Impact of Discontinuing Dornase Alfa in People With CF on Highly Effective CFTR Modulator Therapy-A SIMPLIFY Sub-Study

Summary

Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies in treating cystic fibrosis (CF), it is still largely unknown whether or not other chronic therapies can be safely stopped. This SIMPLIFY sub-study is being done to test whether or not it is safe to stop taking dornase alfa (Dnase) in those people that are also taking elexacaftor/tezacaftor/ivacaftor (ETI).

ETI is a combination CFTR modulator therapy that was approved by the Food and Drug Administration for people with CF who have at least one F508del mutation. The three drugs that make up ETI work together to allow many more chloride ions to move into and out of the cells, improving the balance of salt and water in the lungs. These changes result in better clearance of mucus from the lungs and improvements in lung function.

Dornase alfa (Dnase) also improves clearance of mucus from the lungs to support lung function and has been available to people with CF for many years. Dnase is considered to be relatively burdensome and it is not known whether Dnase can improve or maintain lung function above what is already gained through ETI use.

The goal of this SIMPLIFY sub-study is to get information about whether or not it is safe to stop Dnase by testing if there is a change in lung function in participants with cystic fibrosis (CF) who are assigned to stop taking Dnase as compared to those who are assigned to keep taking Dnase while continuing to take ETI.

This is a sub study of master protocol SIMPLIFY-IP-19, NCT04378153.

The sub study investigating the impact of discontinuing and continuing hypertonic saline is registered under NCT06350461.

Conditions

• Cystic Fibrosis

Interventions

OTHER

Discontinuation of dornase alfa (Dnase)

Discontinuation of current dornase alfa (Dnase) therapy during 6-week study period.

OTHER

Continuation of dornase alfa (Dnase)

Continuation of current dornase alfa (dnase) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily)

Sponsors & Collaborators

• Cystic Fibrosis Foundation

  collaborator OTHER

• Dartmouth-Hitchcock Medical Center

  collaborator OTHER

• University of Washington

  collaborator OTHER

• Nicole Hamblett

  lead OTHER

Principal Investigators

• Nicole Mayer-Hamblett, PhD · University of Washington/Seattle Children's

• Alex Gifford, MD, FCCP · Dartmouth-Hitchcock Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-08-25

Primary Completion

2022-07-11

Completion

2022-07-11

Countries

• United States

Study Locations