Study Results

• What We Learned:

  In adolescents and adults with relatively good lung function on Trikafta®, discontinuing daily use of either hypertonic saline or dornase alfa for 6 weeks did not result in a loss of lung function? as measured by ppFEV1.

   

  Several other studies assessing longer-term effects on health are underway to provide additional insight into the implications of stopping medications and therapies while on Trikafta, including HERO-2 and CF-STORM. 

• Primary Findings:

  Effectiveness:

  This study was conducted between August 2020 and July 2022. The study enrolled 529 participants into one or both trials in the SIMPLIFY study: 370 people were randomized into the HS trial and 477 were randomized into the DA trial.  All participants in the study were clinically stable, using Trikafta® for at least 3 months and had an FEV1 (ppFEV1) >60% predicted. The average age of the SIMPLIFY study cohort was 22 years old with an average ppFEV1 of 97%.

   

  The absolute change in ppFEV1 from baseline (Week 0) to Week 6 in the HS trial was -0.19% (n=133, 95% CI: -0.85,0.48) in the discontinuation arm as compared to 0.14% (n=140, 95% CI: -0.51,0.78) in the continuation arm, reflecting a between-group difference (discontinuation minus continuation) of –0.32% (95% CI: -1.25, 0.60). In the DA trial, a mean 6-week change of 0.18% was observed in the discontinuation arm (n=199, 95% CI: -0.38,0.74) as compared to -0.16% in the continuation arm (n=193, 95% CI: -0.73,0.41), with between-group difference 0.35% (95% CI: -0.45,1.14) (Figure 2).  In both trials, stopping therapy was found to be comparable to continuing therapy with respect to the 6-week change in ppFEV1.

   

  About half of the people in the study were at sites that perform a test called multiple breath washout (MBW). In people with relatively good lung function, this test is better able to detect small changes in lung function compared to FEV1. In SIMPLIFY, there were no clinically important differences in the MBW measurement LCI2.5 between those who continued or stopped either inhaled therapy. Additionally, no clinically meaningful changes in respiratory symptoms were found when using questionnaires including CRISS and CFQ-R There was also no difference in hospitalization, need for antibiotics, or pulmonary exacerbations.  

  In a small group of people, imaging studies called mucociliary clearance (MCC) scans were also done. The mucus clearance from the chest did not worsen in people stopping HS for 6 weeks. It appears to have actually improved in people stopping DA for 6 weeks.

  Safety:

  A small number of people in each trial were found to have new symptoms or health concerns like cough or chest congestion. Though uncommon, these occurred a little more often in those with lower lung function (ppFEV1 60-70%) who were asked to stop their inhaled therapy for 6 weeks. 

• Citation:

  Lancet ;DOI 10.1016/S2213-2600(22)00434-9

For current information about the overall development status of this drug, please check the Drug Development Pipeline.