Dive Brief:
- CytoDyn has secured clearance from an institutional review board to increase dosing in its Phase 3 trial of an experimental HIV treatment, permitting newly enrolled patients and current study participants to receive a higher 700 mg dose of the drug.
- PRO 140 is being tested as a maintenance therapy for the chronic suppression of the HIV virus. At a 350 mg dose given once a week, about 40% of patients on existing antiretroviral treatment were able to sustain viral suppression.
- After a protocol revision allowed for the dose to be increased to 525 mg, a "majority" of non-responders to 350 mg PRO 140 were able to re-suppress at the higher dose. CytoDyn hopes that adding an even higher 700 mg dose will further improve response rates.
Dive Insight:
Adaptive clinical trials allow researchers to make planned changes to the trial design throughout the study based on interim results. This can increase the chance of the trial succeeding and permit patients to switch to a more effective treatment or dose during the study.
Adaptive trials can also cut costs and time to market by making studies more efficient and reducing the number of patients in a study. The Food and Drug Administration put forward draft guidance for the use of adaptive design clinical trials for drugs and biologics in 2010 and recent comments by FDA Commissioner Scott Gottlieb suggest the agency continues to see room for further adoption.
The aim of CytoDyn's study is to support the role of PRO 140 as a long-acting, single-agent maintenance therapy for the chronic suppression of HIV, administered subcutaneously once-weekly at home. While there are a number of effective HIV therapies available, CytoDyn believes there is room for new options that allow for less frequent dosing regimens and trigger fewer side effects.
The study began enrollment of patients in December 2016, with a design created to allow researchers to assess sequentially increasing doses. The dose was first reviewed after 150 patients were treated with 350 mg, and revised to increase the dose to 525 mg for new patients and non-responders.
"We are able to increase the dose of PRO 140 due to its positive safety profile in prior clinical trials. That was among the important factors considered by the IRB in providing this clearance," said Nader Pourhassan, CytoDyn's president and CEO.
According to Pourhassan, the regimen is showing some promise for long-term use. "Patients who achieve suppressed HIV viral load after 10 weeks tend to maintain suppressed viral load. Interestingly, some patients in our Phase 2b extension study are now achieving suppressed HIV viral load for nearly four years with PRO 140 as a single agent," he said.
Recruitment in the CD03 study is expected to complete during 2018, and patients who finish the study will move into a FDA-cleared rollover study.