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CCK-A agonist reduces disease severity in moderate COVID

Rod Tucker
20 April, 2021  

A first-in-class CCK-A agonist has shown benefit in symptom reduction among those hospitalised with moderate COVID-19.

The dual action chemical entity, PNB001, has shown promise as a treatment for those hospitalised with COVID-19. The drug acts as both a cholecystokinin-A (CCK-A) agonist and CCK-B antagonist. Cholecystokinin is a peptide hormone originally identified in the gastrointestinal tract where it serves to mediate pancreatic secretion and contraction of the gall bladder. However, later work has revealed how there are two different types of CCK receptors, and PNB001 has been shown to have both analgesic and anti-inflammatory actions through binding with the different receptors termed A and B. It is the anti-inflammatory effect that is thought to be of greater relevance in COVID-19 and while human safety data on the drug proved to be satisfactory, to date, no trials had been undertaken with COVID-19 patients. In the present study, a team from PNB Vesper Life Science, Kerala, India (the manufacturer of PNB001), examined the impact of their new drug on disease severity scores among those hospitalised with COVID-19. Included patients had pneumonia but not severe disease (defined by an oxygen saturation of < 94%) on room air and with at least two recognised COVID-19 symptoms (e.g., fever, cough, dyspnoea). Excluded patients included those requiring mechanical ventilation. Individuals were randomised to receive either PNB001 (100mg three times daily) along with standard care (SC) or standard care alone which was consistent with India’s current clinical management protocol. Treatment with PNB001 was continued for 14 days and the primary outcome was the change in the 8-point WHO ordinal scale score for disease severity from baseline to day 14 and mortality at day 28.

Findings
A total of 40 patients (20 per arm) were recruited into the study with a mean age (in the PBN001 group) of 52.1 years (30% female). At baseline, both groups had an equal number of patients with a WHO scale score of 4 (i.e., oxygen by mask or nasal prongs). By day 14, the PNB001 group experienced a greater mean reduction in ordinal scale values (0.22 vs 1.12, PNB001 vs SC, p = 0.042) from baseline. For instance, at day 14, 17 (94.4%) vs 12 (70.6%) patients (PNB001 vs SC), had achieved a WHO scale score of 0 (no clinical or virological evidence of infection) and 1 vs 4 patients, maintained a WHO scale score of 4. However, day 28 mortality was similar in both groups although a higher proportion of patients given PNB001 were discharged from hospital by day 14 (19 vs 15, p = 0.048).

In their conclusion, the authors noted that PNB001 was well tolerated and that it showed significant clinical improvements when added to standard care in patients with moderate COVID-19. However, they also recognised the limitations of the study, i.e., a small sample size and the fact that while randomised, it was not blinded.

Citation
Lattmann E et al. Randomised, Comparative, Clinical Trial to Evaluate Efficacy and Safety of PNB001 in Moderate COVID-19 Patients. MedRxiv 2021