Feasibility of placebo-controlled trial designs for new CFTR modulator evaluation

New CFTR modulators are in development that sponsors anticipate will be comparable or superior to approved modulators. Testing these agents for efficacy will require either placebo-controlled or active-comparator trials.

We surveyed US CF physicians and their patients eligible to receive approved modulators or their families for willingness to participate in placebo-controlled modulator trials of varying duration.

Interest in placebo-controlled trials of short duration (2-4weeks) was greatest, with few respondents, particularly among patient respondents, willing to consider 6month studies. Patients/families with access to approved modulators were consistently less interested in placebo-controlled modulator trials of any duration.

Sample size and interpretability advantages of placebo-controlled trials outweigh alternative active-comparator trials, but must consider physician and patient thresholds for forgoing treatment with approved modulators. Enrollment will be most feasible for short-duration trials and those conducted among populations without access to approved modulators.