NCT04549922

Antisense Therapy to Block the Kallikrein-kinin Pathway in COVID-19

Antisense Therapy to Block the Kallikrein-kinin Pathway in COVID-19: A Phase II Randomized Controlled Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 111 (actual)
• Sponsor: Hospital do Coracao · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Up to 1/3 of all patients infected with COVID-19 can develop complications that require hospitalization. Severe pneumonia associated with acute respiratory distress syndrome (ARDS) is the most threatening and feared complication of COVID-19 infection, with mortality rates close to 50% in some groups. Autopsies between these severe cases reveal severe capillary involvement, with signs of intense inflammatory changes, microvascular thrombosis, endothelial injury and abnormal tissue repair. The available evidence suggests that abnormal activation or imbalance in the counter-regulation of the kallikrein-kinin system may play a central role in a positive feedback cycle, leading to consequent diffuse microangiopathy. Blockade of the kallikrein-kinin system can therefore prevent deterioration of lung function by reducing inflammation, edema and microthrombosis. The objective of this phase IIb study is to assess the preliminary effects on the oxygenation parameters of an antisense oligonucleotide that inhibits pre-kallikrein synthesis in patients with moderate to severe COVID-19.

Detailed description

The objective of this phase IIb study is to assess the preliminary effects on the oxygenation parameters of an antisense oligonucleotide that inhibits pre-kallikrein synthesis in patients with moderate to severe COVID-19. This is a blind randomized pilot clinical study which aims to include 110 patients (55 per arm).

Conditions

• Covid19

Interventions

Type	Name	Description
DRUG	ISIS 721744	1.2 mL of ISIS 721744 subcutaneous once after randomization
DRUG	Normal Saline	1.2 mL subcutaneous

Timeline

• Start date: 2020-10-19
• Primary completion: 2020-12-09
• Completion: 2021-12-09
• First posted: 2020-09-16
• Last updated: 2022-09-22

Locations

3 sites across 1 country: Brazil