Ashvattha Therapeutics is planning a trial of OP-101 in Long Covid

RedFox

RedFox

Senior Member (Voting Rights)
A drug company called Ashvattha Therapeutics is working on a new drug candidate for long Covid, OP-101.
Link: Ashvattha previews plans for long Covid trial in mid-2023
Two years after beginning a Phase IIa trial of OP-101 in severe Covid-19 infections, Ashvattha Therapeutics is now pivoting to long Covid with the same drug. The California-based biotech is in discussions with the FDA to run a 300–400 patient trial of OP-101 in long Covid patients beginning in mid-2023, CEO Jeff Cleland tells Clinical Trials Arena.
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Key takeaways:
  • OP-101 was originally developed for neurodegenerative disease
  • They're discussing their plans with the FDA so nothing is set in stone. Potentially phase IIa trial with 300-400 participants. Patients will have LC and elevated C-Reactive protein.
  • They hope they can get approval after just one trial (I'm skeptical)
  • It's supposed to reduce inflammation by acting on macrophages and microglia
  • Outcome measures might be lung function, fatigue scores, and cognitive testing.
The fact that OP-101 affects microglia connects with Jared Younger's research and the neuroinflammation hypothesis, which I'm a fan of.
 
Although the Phase IIa trial (NCT04458298) of OP-101 reported positive results in July, Cleland says acute Covid-19 no longer makes sense as a target indication. With vaccines and antivirals now widely available in the US, it has become increasingly difficult to recruit patients with severe Covid-19 and demonstrate a significant survival benefit in trials, he explains.
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My first thought was, 'yeah, right, it didn't work out for Covid-19 and so now they have a snake oil drug looking for a disease'. But actually their Phase IIA trial in acute Covid-19 was pretty decent, and it did indicate that the drug might help clinical outcomes.
Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial

The sample size was small and I'm sure there were complicating factors, such as random differences in when patients were given steroids, and with their comorbidities. But even so, the results still looked interesting. Here for example, are levels of markers of neurological injury (red dots are the patients who died).

Screen Shot 2022-08-13 at 5.39.47 pm.png

I thought this was interesting about the drug potentially being useful in periperhal neuropathy.
Neurological and psychiatric complications occur frequently after COVID-19 hospitalization, especially after severe COVID-19 (41). Brain injury markers such as NfL, GFAP, and Tau are elevated in hospitalized patients with COVID-19 (42) and are associated with worse outcomes and increased mortality (9, 10, 43, 44). We found an increase in serum NfL and GFAP over time in patients given placebo, which was attenuated in OP-101–treated patients. Of note, NfL lacks specificity for the CNS and has also been shown to be elevated in patients with peripheral neuropathies and chronic inflammatory demyelinating polyneuropathy (45). Although we did not have cerebrospinal fluid (CSF) samples available to assess CNS NfL, strong correlations have been shown between CSF and blood concentrations of NfL, suggesting a unifying pathophysiological process (46). It is possible that an increase in NfL may be due to peripheral neuropathy in patients with severe COVID-19. Peripheral nerve injury has been described after COVID-19 and may be associated with macrophage activation and immune dysregulation (47).
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I can't recall if levels of NfL have been looked at in ME/CFS, probably they have and nothing was found. The trial for Long Covid sounds as though it isn't really targeting the ME/CFS sort of Long Covid, with its selection of patients with high CRP and the primary outcome of lung function.

The study will select patients with elevated C-reactive protein (CRP) levels, a widely used bloodstream biomarker of inflammation, Cleland says. In the previous Phase IIa trial, OP-101 reduced CRP levels and overall inflammation in patients with severe Covid-19.

As a primary outcome, Ashvattha is considering lung function, which has been an approvable endpoint in idiopathic pulmonary fibrosis, Cleland says. For a possible co-primary or secondary endpoint, Ashvattha will likely use a fatigue test score, he adds.

Ashvattha will also likely include a cognitive test as a secondary outcome, Cleland says. However, this endpoint will probably not achieve statistical significance, as that would likely require close to 1,000 patients, he notes.
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