A Randomized, Comparative Clinical Trial to Evaluate Efficacy and Safety of PNB-001 as Immune Modulator in Moderate COVID-19 Patients

Introduction: Several therapeutic agents are being evaluated for the treatment of coronavirus disease 2019 (COVID-19). PNB-001 is a potent anti-inflammatory agent with immune stimulation properties. It is a first in class CCK A agonists and CCKB antagonist, being responsible for its unique action. Methods: We conducted a multi-centre, randomized, parallel group, comparative, open label study to assess efficacy and safety of PNB-001 in patients with moderate COVID-19 infection. Patients were randomly assigned to receive PNB-001 100 mg orally with Best Care BC (PNB 001 + BC) or only Best Care (BC). A total of 40 patients (20 in Adjunct and 20 in BC arm) were randomised and received treatment. Results: The primary endpoint, change in the 8-point WHO Ordinal Scale score for COVID-19 showed significant Clinical Improvement from baseline to day 15 with PNB 001 + BC (P=0.042). Death rate, one patient on PNB 001+BC and two patients in BC arm died (1 Vs 2; HR: 2.0 [95%CI=0.18, 22.05]; P=0.56) by Day 28. Mean Chest X-ray score showed significant improvement (2.05 Vs 1.16; P=0.032) as well as more patients quickly showed complete improvement. Patients needed shorter duration of hospitalization and on day 15, 1 patient was hospitalised on adjunct compared to 5 on BC (P=0.048), thus giving 80% of reduction on the hospitalisation parameter. Mean duration of supplemental oxygen requirement was shorter. 50% of patients were off oxygen on day 6 on adjunct compared to day 8 on BC. Exploratory analysis done for ESR, CRP, IL-6, and N/L ratio and immune parameters showed a statistically significant reduction by Day 15. Lymphocytes were increased into the reference range (P=0.032) and neutrophils were reduced (P=0.013). The role of PNB-001 as immune modulator was clearly established. NLR was reduced significantly for adjunct compared to BC. A total of 24 (11 Vs 13) adverse events were reported in 18 (8 Vs 10) patients and none of the 11, were related to PNB-001. Overall safety profile was found better in test than control arm. Conclusion: PNB-001 when combined with BC improved the clinical status of patients with moderate COVID-19 infection compared to BC alone. Hospitalisation and dead rate was further reduced by 80% and 50%, respectively. PNB-001 was well tolerated by patients with moderate COVID-19 and acted by stimulation of the immune system. Key Findings: Anti-inflammatory activity was improved further for test agent PNB-001 even in presence of potent steroids. The immune stimulating properties of PNB-001, analysed in form of NLR, are key to fight COVID-19 infection. NLR was found highly useful as predictive and clinical biomarker and it was significantly reduced by PNB-001.