Phase III
Phase III trials are the pivotal and confirmatory clinical trials
required to demonstrate benefit and support approval of a new therapy.
While safety continues to be carefully monitored, the primary focus of
Phase III trials is efficacy. These studies are conducted in a
randomized, blinded fashion and compare the candidate drug either to a
placebo or, if it would not be considered ethical to withhold, standard
treatment. The scope and design of Phase III trials are often negotiated
with regulators prior to trial initiation. The candidate drug must be
manufactured and administered in the same manner as would be expected
after completion of the clinical trial. In CF, these studies may enroll
anywhere from 200 to 600 participants, though these studies may be much
larger in more common disease conditions. Phase III trials require
multiple institutions to participate, and may include international
sites. Two successful “adequate and well-controlled” (21 CFR 314.126)
Phase III clinical trials are typically required to obtain FDA approval;
these may be conducted in parallel. In some cases, regulatory agencies
have negotiated with sponsors to consider drug approval with a single
Phase III trial if there is a supporting Phase II study conducted under
similar conditions, i.e., randomized, controlled, blinded, etc. Because
CF drugs have been chronic therapies, extended safety data is needed,
even when clinical benefit is seen after a short interval (e.g., CFTR
modulators). This has led to most studies being at least 6 months long.
In addition, GCP requires 12 months of drug exposure to assess safety,
so many studies have open-label follow up evaluations.