Table 1.
The study design and outcome measure will vary with the development phase of an anti-inflammatory therapy.
| Phase of development | Population | Duration | Outcome measures | Example |
|---|---|---|---|---|
| Preclinical study | Animal models In vitro assays |
Days |
Safety
Lack of negative effect on airway infection |
CFTR-deficient mouse model to investigate infection susceptibilities associated with study drug (Bonfield, 2020) |
| Phase I | Healthy volunteers or Non-CF patients | ≤3 months | Safety and pharmacokinetics | Phase 1 study of acebilistat in CF patients and healthy volunteers (Elborn et al., 2017) |
| Phase IIa | CF adults | 8–12 weeks |
Biomarkers
e.g. sputum NE, IL-6, IL-8 serum CRP, calprotectin Trends in a reduction in PEx New imaging techniques e.g. MRI, PET-CT Functional tests e.g. MBW |
Phase II randomized placebo-controlled trial of acebilustat 48-week study Primary endpoint: change in FEV1pp and safety outcomes Secondary outcomes: PEx rate, time to first PEx and biomarkers of inflammation (Elborn et al., 2018) |
| Phase IIb/III | CF adolescents and adults | ≥6 months |
PEx rate
FEV1 decline Evolution of bronchiectasis on CT |
Phase IIb placebo-controlled trial of lenabasum in cystic fibrosis. 28-week study Primary outcome: PEx rate Secondary outcomes: time to first PEx; PEx rate using secondary PEx definition; change in CFQ-R Respiratory domain score; Change in FEV1pp; Adverse events (Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic Fibrosis—Full Text View—ClinicalTrials.gov) |
| Alternative study design | CF adolescents and adults | Treatment during PEx |
FEV1 change with treatment
FEV1 recovery post treatment Biomarkers |
Randomized placebo-controlled trial Of prednisone in cystic fibrosis PEx Primary outcome the proportion of subjects who achieve >90% of baseline FEV1% predicted at day 14 of IV antibiotic treatment (Prednisone in Cystic Fibrosis Pulmonary Exacerbations - Full Text View - ClinicalTrials.gov) |
NE, neutrophil elastase; CRP, C-reactive protein; CFQ-R, Cystic Fibrosis Questionnaire- Revised; MRI, magnetic resonance imaging; PET-CT positron emission tomography – computed tomography; PEx; pulmonary exacerbation; FEV1pp, FEV1 percent predicted; MBW, multiple breath washout.
Key outcome measures in bold, potential future outcome measures in italics.