A phase 2 study of the inhaled pan-JAK inhibitor TD-0903 in severe COVID-19: Part 1

  1. Dave Singh
  2. Maxim Bogus
  3. Valentyn Moskalenko
  4. Robert Lord
  5. Edmund J. Moran
  6. Glenn D. Crater
  7. David L. Bourdet
  8. Nathan D. Pfeifer
  9. Jacky Woo
  10. Elad Kaufman
  11. David A. Lombardi
  12. Emily Y. Weng
  13. Tuan Nguyen
  14. Ashley Woodcock
  15. Brett Haumann
  16. Rajeev Saggar
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Abstract

Background

Lung-targeted anti-inflammatory therapy could potentially improve outcomes in patients with COVID-19. The novel inhaled pan-Janus kinase (JAK) inhibitor TD-0903 was designed to optimise delivery to the lungs while limiting systemic exposure. Here, we report results from the completed Part 1 of a 2-part phase 2 trial (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04402866">NCT04402866</ext-link>) in hospitalised patients with severe COVID-19.

Methods

Part 1 explored 3 doses of TD-0903 (1, 3, and 10 mg once-daily for 7 days) and placebo in a randomised, double-blind, ascending-dose study. Each dose cohort comprised 8 hospitalized patients (6:2 TD-0903:placebo) with PCR-confirmed COVID-19 requiring supplemental oxygen and receiving background standard-of-care therapy. Key objectives included safety and tolerability, pharmacokinetics, and oxygen saturation/fraction of inspired oxygen ratio; clinical outcomes were also explored. Data were summarised as descriptive statistics.

Results

Twenty-five patients were randomised to receive TD-0903 1 mg (n = 6), 3 mg (n = 7), 10 mg (n = 6), or placebo (n = 6). Almost all patients (92%) received background dexamethasone; 3 (12%) received remdesivir. TD-0903 was generally well tolerated with no drug-related serious adverse events. Low plasma concentrations of TD-0903 were observed at all doses. Clinically favourable numerical trends in patients receiving TD-0903 vs placebo included improved 8-point clinical status, shortened hospitalisation, improved oxygenation, and fewer deaths.

Conclusions

In Part 1 of this phase 2 trial, the novel inhaled JAK inhibitor TD-0903 showed potential for treatment of patients with severe COVID-19. TD-0903 3 mg is being evaluated in Part 2 of the randomised, double-blind, parallel-group trial in 198 hospitalized patients with COVID-19.

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