NCT06350474: SIMPLIFY-DN

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

Completed NA Results posted Last updated 26 November 2024

What this trial tests

NA trial testing Discontinuation of dornase alfa (Dnase) in Cystic Fibrosis in 477 participants. Completed in 11 July 2022.

Timeline

25 August 2020

Primary endpoint
11 July 2022

11 July 2022

Quick facts

Lead sponsor	Nicole Hamblett
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	other
Enrollment	477
Start date	25 August 2020
Primary completion	11 July 2022
Estimated completion	11 July 2022
Sites	81 locations across United States

Drugs / interventions tested

• Discontinuation of dornase alfa (Dnase)
• Continuation of dornase alfa (Dnase)

Conditions studied

• Cystic Fibrosis — all drugs for Cystic Fibrosis →

Sponsor

Nicole Hamblett

Who can join

12 and older, any sex, with Cystic Fibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Absolute Change in FEV1 % Predicted From Week 0 to Week 6 Primary · Week 0 to Week 6

Non-Inferiority statistical testing compared difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.

Group	Value	95% CI
Dnase - Discontinue	0.2	± 3.69
Dnase - Continue	-0.2	± 4.37

Absolute Change in LCI 2.5 From Baseline to Week 6 Secondary · Baseline (Week 0 or Week -2) to Week 6

Statistical testing compared difference between study arms (discontinue - continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Baseline (Week 0, if available, or else Week -2) to Week 6. LCI 2.5 is the number of times the volume in the lungs needs to turn over to expel an inert gas. A higher value of LCI 2.5 indicates poorer lung function.

Group	Value	95% CI
Dnase - Discontinue	-0.1	± 0.63
Dnase - Continue	0.0	± 0.56

Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6 Secondary · Week 0 to Week 6

Statistical testing compared the difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) from Week 0 to Week 6. The Cystic Fibrosis Respiratory Symptoms Daily Diary (CFRSD) asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the

Group	Value	95% CI
Dnase - Discontinue	-0.1	± 9.49
Dnase - Continue	-1.1	± 10.21

Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6 Secondary · Week 0 to Week 6

Statistical testing compared the difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score from Week 0 to Week 6. The Cystic Fibrosis Questionnaire - Revised asks participants 6 questions related to respiratory symptoms which are each assigned a score 1-4. The Respiratory Domain Scaled Score is calculated as follows: 100\*\[{sum of responses}/{number of responses}-1\]/3 only if number of responses ≥ 3; otherwise the score is set to missing. The scaled score ranges from

Group	Value	95% CI
Dnase - Discontinue	-0.9	± 6.23
Dnase - Continue	0.0	± 8.85

Absolute Change in FEV1 % Predicted From Week -2 to Week 0 Secondary · Week -2 to Week 0

Statistical testing compared the difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.

Group	Value	95% CI
Dnase - Discontinue	0.2	± 3.11
Dnase - Continue	0.0	± 3.79

Absolute Change in FEV1 % Predicted From Week 0 to Week 2 Secondary · Week 0 to Week 2

Statistical testing compared the difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.

Group	Value	95% CI
Dnase - Discontinue	-0.1	± 3.67
Dnase - Continue	0.1	± 3.96

Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6 Secondary · Week 0 to Week 6

Difference between study arms (discontinue - continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6. Includes antibiotics initiated for respiratory indications; excludes those taken as part of a chronic cycled regimen or for a UTI, skin infection, etc.

Group	Value	95% CI
Dnase - Discontinue	14
Dnase - Continue	8

Number and Percent of Participants Hospitalized From Week 0 to Week 6 Secondary · Week 0 to Week 6

Statistical testing compared the difference between study arms (discontinue - continue) in the percent of subjects hospitalized from Week 0 to Week 6.

Group	Value	95% CI
Dnase - Discontinue	0
Dnase - Continue	0

Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6 Secondary · Week 0 to Week 6

Statistical testing compared the difference between study arms (discontinue - continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6. Pulmonary exacerbations defined using Fuchs criteria.

Group	Value	95% CI
Dnase - Discontinue	4
Dnase - Continue	2

Number and Percent of Participants Experiencing Adverse Events (AEs) From Week 0 to Week 6 Secondary · Week 0 to Week 6

Statistical testing compared the difference between study arms (discontinue - continue) in the percent of participants with at least one AE from Week 0 to Week 6. Includes serious and non-serious AEs.

Group	Value	95% CI
Dnase - Discontinue	89
Dnase - Continue	55

Rate of Adverse Events (AEs) From Week 0 to Week 6 Therapy Arms Secondary · Week 0 to Week 6

Statistical testing compared the compared the rate of AE occurrence (number of events divided by total follow-up weeks in each arm) between study arms from Week 0 to Week 6. Includes serious and non-serious AEs.

Group	Value	95% CI
Dnase - Discontinue	0.116
Dnase - Continue	0.060

Number and Percent of Participants With Temporary or Permanent Changes From Assigned Therapy Regimen Due to Adverse Event From Week 0 to Week 6 Secondary · Week 0 to Week 6

Statistical testing compared the difference between study arms (discontinue - continue) in the percent of subjects temporarily or permanently changing their assigned therapy regimen due to an adverse event Week 0 to Week 6

Group	Value	95% CI
Dnase - Discontinue	7
Dnase - Continue	2

Adverse events — posted to ClinicalTrials.gov

Time frame: From randomization (Week 0) up to last study visit (Week 6), i.e., 6 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dnase - Discontinue

Serious: 0/240 (0%)

Deaths: 0/240

Dnase - Continue

Serious: 0/237 (0%)

Deaths: 0/237

Other adverse events (2 terms — click to expand)

Reaction	System	Dnase - Discontinue	Dnase - Continue
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—

Data from ClinicalTrials.gov NCT06350474 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.