Table 3 –
Example of a Future Study Design Package for a New CFTR Modulator to Address Global Requirements for Efficacy and Safety
| Example Studies Contributing to a Comprehensive Package | |||||
|---|---|---|---|---|---|
| Study Design Attributes | Short Placebo-Controlled Trial (2 weeks - <1 mos.) | Open-Label, Prescription Reliant Active Comparator1 Trial (3–6 mos.) | Open-label Active Arm Safety Study2 (1 year) | Retrospective Study: Historical Control vs. Pooled Active Arms across Studies (6 mos.−1 year) | Combined Attributes from All Studies |
| Comparator Group | √ | √ | - | √ | √ |
| Blinded Treatment Arms | √ | - | - | - | √ |
| Superiority Hypothesis | √ | - | - | √ | √ |
| Non-Inferiority Hypothesis | - | √ | - | - | √ |
| Clinical Efficacy Evaluation | √ | √ | - | √ | √ |
| Short term | √ | √ | - | - | √ |
| Long term | - | ?1 | - | √ | √ |
| FEV1 | √ | √ | - | √ | √ |
| PEx | - | - | - | √3 | √ |
| Safety Evaluation | √ | √ | √ | - | √ |
| Short term | √ | √ | √ | - | √ |
| Long term | - | ?1 | √ | - | √ |
FEV1= forced expiratory volume in one second, PEx= pulmonary exacerbation
Duration of the active-comparator dependent on feasibility of reliance on prescription-based therapy, as well as a duration that mitigates risk of confounding due to access by both treatment arms to study drug. Duration of the trial will drive ability of the study to address long term efficacy and safety.
Open label safety study would be a follow-on study for participants in the placebo and active-controlled trial, in addition to a free-standing study to enroll additional participants and increase the size of the safety database.
Assessment of a pulmonary exacerbation-related endpoint dependent on availability of a consistent definition across databases.