On the pages of oncology clinical trials on the database ClinicalTrials.gov, the section listing the various criteria that patients must meet for enrollment commonly includes a line stating that patients with hepatitis B, hepatitis C or HIV are excluded. But under a new Food and Drug Administration draft guidance, that could change.
Issued Tuesday, it is part of a serious of draft guidances regarding cancer clinical trial eligibility criteria. While not binding, it suggests potentially allowing patients with HBV, HCV and HIV into clinical trials, as long as they meet certain conditions. Other documents in the series concern the minimum age for pediatric patients, organ dysfunction and cancer history, brain metastases and a final guidance on the inclusion of adolescent patients in adult trials.
Clinical trial design is a delicate affair. A key component is a study’s inclusion and exclusion criteria. These are the rules that govern which patients can enter the study based on considerations such as age, stage or severity of disease, various lab test results and more. If those criteria are too tightly defined, it can encumber patient recruitment, which in turn can slow down the trial and complicate plans like presentation and publication of data. On the other hand, eligibility criteria that are too loose can complicate interpretation of those data or even put patient safety at risk.
But while most eligibility criteria have a solid rationale behind them, some are simply included by default across trials, without a clear rationale, according to the FDA draft guidance. “Unnecessarily restrictive eligibility criteria may slow patient accrual, limit patients’ access to clinical trials, and lead to trial results that do not fully represent treatment effects in the patient population that will ultimately use the drug,” the guidance read.
Some sponsors have loosened such default eligibility requirements without experiencing any problems. For example, in 2016, Juno Therapeutics – which Celgene acquired last year for $9 billion – amended the protocol of its Phase I clinical trial of the CAR-T lisocabtagene maraleucel to let in diffuse large B-cell lymphoma patients with central nervous system involvement secondary to the disease. The amendment was in response to data showing that the CAR-T was effective without producing neurotoxicity in those patients. By contrast, competing CAR-T studies in DLBCL at the time continued excluding patients with secondary CNS involvement.
The draft guidance Tuesday stated that for patients with HIV, those who have CD4-positive T-cell counts of 350 or more per microliter should generally be eligible for any study. Those with lower counts should be generally eligible if they have potentially curable cancers or the trials are for interventions in later-stage development that have demonstrated prior activity. Those without a history of AIDS-defining opportunistic infections should also be generally eligible, while those with such a history should be considered possibly eligible, depending on various conditions. Other considerations were also included for patients taking various antiretroviral drugs. For HBV and HCV, the draft guidance suggested that most patients should have the same liver-related lab test results as the general population, with requirements for some liver cancers being less stringent. They should also have viral loads under control, it stated.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Photo: FDA, Flickr
