NCT06127498

The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray

A Randomized, Double-blind, Placebo-parallel Controlled Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of A8G6 COVID-19 Neutralizing Antibody Combination Nasal Spray in Healthy Subjects

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 108 (estimated)
• Sponsor: The Second Affiliated Hospital of Chongqing Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This is a randomized, double-blind, placebo-parallel intervention clinical study that will include approximately 108 healthy subjects based on inclusion and exclusion criteria. Patients meeting inclusion and exclusion criteria were randomly assigned to one of four different cohorts. Subjects in each cohort were randomly assigned 5:1 to two parallel administration groups, one of which served as a control. Each cohort was given either the experimental drug or placebo by nasal spray at different doses and intervals, and blood was collected on an empty stomach before the first dose. Right nostril and nasal swabs were collected for immunotoxicity, immunogenicity (immunogenicity collection and detection in cohorts 3 and 4 only), and drug concentration detection. Subjects in the first three cohort were required to return to the study Center 3±1 days after the last dose for blood samples, bilateral nostril and nasal swabs for drug concentration, immunotoxicity, physical examination, vital signs, and safety laboratory indicators (blood routine, blood biochemical, and urine routine). Subjects in cohort 4 returned to the study center 7±2 days after the last dose. To evaluate the safety and tolerability of A8G6 COVID-19 neutralization and antibody combined nasal spray in healthy subjects by comparing the test results of subjects in different cohorts, and to study its concentration in serum and nasal swabs in healthy subjects.

Detailed description

As of May 11, 2022, more than 519 million COVID-19 cases and 6.28 million deaths have been reported worldwide, according to Worldometer Real-time statistics. On November 27, 2021, a large number of highly transmissible mutated new variants of COVID-19 were found in South Africa, which was named Omicron (including subtypes BA.1 and BA.2) by WHO. Although the introduction of vaccines has played a great role in the prevention and control of COVID-19, the neutralizing antibodies stimulated by different vaccines differ greatly, and the antibody maintains a high titer in the human body for a short time (3-6 months at most), so the global demand for safe and effective prevention of COVID-19 remains unmet. The novel coronavirus neutralizing antibody can directly bind to the envelope of the novel coronavirus to rapidly block the virus infection, which has been fully verified as a safe and effective treatment. But so far, there are no approved antibodies at home or abroad to prevent infection with the novel coronavirus, In addition, there is a lack of broad-spectrum monoclonal neutralizing antibodies with high efficiency against mutant strains (currently, all the approved neutralizing antibodies in the world are used in combination with two antibodies), which can be used as reference for the administration of neutralizing antibodies for the prevention of a wide range of people (intravenous infusion as the prophylactic administration will lead to low compliance of the administration population). MY-586 and MY-558, two active components of the novel coronavirus neutralizing antibody A8G6, were screened from peripheral blood lymphocytes of patients recovering from COVID-19, from which 209 strains of novel coronavirus specific antibodies were isolated. The screened MY-586 is a super antibody with strong and effective neutralization against the novel coronavirus and the circulating British strain, Indian strain, South African strain and Indian Delta strain. Its high affinity, high level and activity against the novel coronavirus, broad-spectrum variant strain activity and antibody structure analysis supporting superior activity. It has been published in the authoritative international journal Nature Communications. MY-558 is a super antibody with high affinity, high activity and high affinity to both the novel coronavirus and Omicron (BA.1 and BA.2) strains, and the binding regions of MY-586 and MY-558 and RBD do not overlap, so there is no competitive relationship between the two. On the contrary, the two have certain synergistic effects on each novel coronavirus strain. Among the COVID-19 neutralizing antibodies published worldwide, A8G6 antibody has one of the best affinity and neutralizing activity against COVID-19. At present, the evaluation of the preclinical efficacy and safety of A8G6 combined antibody and the production of CMC to support the clinic are nearing completion. All the data showed that the A8G6 combined antibody had excellent efficacy, safety and druggability. In particular, A8G6 combined antibody is administered by nasal spray. Although there are no approved nasal spray neutralizing antibody drugs on the market at home and abroad, the investigators have successfully solved the drugging of A8G6 combined antibody by nasal spray and the development of nasal spray device. Nasal spray type A8G6 combined antibody is easy to carry, easy to administer, and has strong accessibility and compliance for the population. It can be used as a new and widely used safe and effective preventive measure besides vaccine. Therefore, the rapid and successful clinical research and development of A8G6 combined antibody will provide a more effective guarantee for social security and effective prevention of COVID-19.

Conditions

• SARS-CoV-2
• Prevention

Interventions

Type	Name	Description
BIOLOGICAL	A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray	Subjects in each cohort were randomly assigned 5:1 to two parallel administration groups, one of which served as a control. Each cohort was given either the experimental drug or placebo by nasal spray at different doses and intervals, and blood was collected on an empty stomach before the first dose. Right nostril and nasal swabs were collected for immunotoxicity, immunogenicity (immunogenicity collection and detection in cohorts 3 and 4 only), and drug concentration detection. Subjects in the first three cohort were required to return to the study Center 3±1 days after the last dose for blood samples, bilateral nostril and nasal swabs for drug concentration, immunotoxicity, physical examination, vital signs, and safety laboratory indicators (blood routine, blood biochemical, and urine routine). Subjects in cohort 4 returned to the study center 7±2 days after the last dose.
OTHER	A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient	Subjects in each cohort were randomly assigned 5:1 to two parallel administration groups, one of which served as a control. Each cohort was given either the experimental drug or placebo by nasal spray at different doses and intervals, and blood was collected on an empty stomach before the first dose. Right nostril and nasal swabs were collected for immunotoxicity, immunogenicity (immunogenicity collection and detection in cohorts 3 and 4 only), and drug concentration detection. Subjects in the first three cohort were required to return to the study Center 3±1 days after the last dose for blood samples, bilateral nostril and nasal swabs for drug concentration, immunotoxicity, physical examination, vital signs, and safety laboratory indicators (blood routine, blood biochemical, and urine routine). Subjects in cohort 4 returned to the study center 7±2 days after the last dose.

Timeline

• Start date: 2022-05-01
• Primary completion: 2023-12-01
• Completion: 2023-12-01
• First posted: 2023-11-13
• Last updated: 2023-11-13

Locations

1 site across 1 country: China