Concussion Treatment PRV-002 Demonstrates Safe, Tolerable Profile in Phase 1 Trial

Dallas Hack, MD

According to a recent announcement, Odyssey Health’s investigational agent PRV-002, a fully synthetic nonnaturally occurring neurosteroid intended to treat concussion, was safe and tolerated in a small cohort of healthy volunteers. The company is currently selecting clinical sites and developing the Investigator’s Brochure for an upcoming phase 2 trial.¹

In cohort 1 of the multiday ascending dose (MAD) trial, 8 healthy human volunteers were randomly assigned 1:1 to ether 1 dose of PRV-003 or placebo for 5 consecutive days. Evaluated by the Safety Review Committee, no serious adverse events were recorded, and all patients demonstrated normal vital signs, electrocardiogram readings, and breathing function. In total, the phase 1 trial was designed with 6 cohorts comprised of 8 individuals each, with data expected to be reported after each cohort is completed.

"After reviewing the data from MAD Cohort I, I have strong confidence that PRV-002 will continue to show safety during the final, high-dose MAD portion of the phase 1 clinical trial. We have unanimously approved the start of MAD Cohort II," Dallas Hack, MD, member of the Safety Review Committee, said in a statement.¹ "The overall low levels of PRV-002 in the blood support the hypothesis that more drug is getting to the brain itself when administered with the intranasal device. If this turns out to be the case, not only can the targeted effects of the drug be more efficacious, but the drug will also likely have fewer potential side effects.”

Conducted at Nucleus Network, for each of the 5 days of dosing, pharmacokinetic analysis showed a direct relationship between drug dosing concentration and blood plasma levels. Additionally, blood levels of the active drug were significantly lower on average with intranasal administration than what would be expected with other routes of delivery. Furthermore, there was no appreciable accumulation of PRV-003 with consecutive day treatments, as well as no alterations in blood samples using multiday treatment.

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Philip Ryan, MD, principal investigator for Nucleus Network, said in a statement that, "the Safety Review Committee has confidence about the safety of the intranasal delivery of PRV-002. We look forward to completing the final high-dose MAD portion of the Phase I trial and assisting Odyssey with their Phase II/III design to determine the efficacy of PRV-002 for concussed patients."¹

In preclinical animal studies, PRV-002 has shown to reduce the behavioral pathology associated with brain injury symptoms such as memory impairment, anxiety, and motor/sensory performance. Additionally, the agent is lipophilic and can easily cross the blood-brain barrier to rapidly eliminate swelling, oxidative stress, and inflammation in the brain while restoring proper blood flood.

Currently, there is a lack of FDA-approved therapies for concussions, though a few additional agents are being investigated. Recently, in mid-August 2022, Oxeia Biopharmaceuticals announced positive interim progress for a phase 2 trial (NCT04558346) evaluating its investigational therapy OXE103 for the treatment of concussion. Although no specific data were released, the company did note they will be presenting the results at an upcoming conference once the final topline dataset is available. OXE103 is a twice-daily injectable identical formulation of the protein ghrelin, which is secreted by the human stomach. In preclinical studies, OXE103 administration has been shown to restore normal energy metabolism, increase appetite, and reduce the toxic effects of reactive oxygen species.

REFERENCES
1. Odyssey Health achieves positive safety outcomes for concussion drug in multiple ascending dosing trial. Odyssey Health. August 18, 2022. Accessed August 23, 2022. https://www.globenewswire.com/news-release/2022/08/18/2500777/0/en/Odyssey-Health-Achieves-Positive-Safety-Outcomes-for-Concussion-Drug-in-Multiple-Ascending-Dosing-Trial.html
2. Oxeia announces positive interim results of phase 2 trial for OXE103 for the treatment of concussions. News release. Oxeia. August 3, 2022. Accessed August 23, 2022. https://www.globenewswire.com/news-release/2022/08/03/2491668/0/en/OXEIA-ANNOUNCES-POSITIVE-INTERIM-RESULTS-OF-PHASE-2-TRIAL-FOR-OXE103-FOR-THE-TREATMENT-OF-CONCUSSIONS.html