This is a randomized, double-blind, placebo-parallel intervention clinical study thatwill include approximately 108 healthy subjects based on inclusion and exclusioncriteria. Patients meeting inclusion and exclusion criteria were randomly assigned to oneof four different cohorts. Subjects in each cohort were randomly assigned 5:1 to twoparallel administration groups, one of which served as a control. Each cohort was giveneither 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 andnasal swabs were collected for immunotoxicity, immunogenicity (immunogenicity collectionand detection in cohorts 3 and 4 only), and drug concentration detection. Subjects in thefirst three cohort were required to return to the study Center 3±1 days after the lastdose 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 tothe study center 7±2 days after the last dose. To evaluate the safety and tolerability ofA8G6 COVID-19 neutralization and antibody combined nasal spray in healthy subjects bycomparing the test results of subjects in different cohorts, and to study itsconcentration in serum and nasal swabs in healthy subjects.
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.
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.
Inclusion Criteria:
1. Subjects fully understand the purpose, nature, method and possible adverse reactions
of the experiment, voluntarily participate in the experiment, and sign informed
consent before the experiment begins;
2. Healthy subjects aged 18-65 years (including the critical value) with an appropriate
sex ratio between men and women;
3. The subjects had no birth plan for 3 months from the date of signing the informed
consent to the end of the study, and agreed to voluntarily take effective and
appropriate contraceptive measures with their partners during this period;
4. The subject agrees that from the beginning of the study (-1 day) to the end of the
study, except for this study, only samples of NCOV nucleic acid from throat swabs
will be taken, and nasal swabs will not be taken;
5. The subjects had not received any type of NCOV vaccine within 3 months prior to
enrollment, and had no NCOV vaccination plan during the study period;
6. Subjects can communicate well with researchers and understand and comply with the
requirements of this study.
Exclusion Criteria:
1. Allergic to any ingredient in this product and auxiliary materials; Or allergic
(such as allergic to two or more drugs, food);
2. Patients with symptoms of acute upper respiratory tract infection within 1 week
before administration;
3. Patients with acute episodes of chronic rhinitis or anatomical abnormalities
affecting drug absorption in the nose;
4. Patients with a history of asthma;
5. Asplenia or functional asplenia caused by any condition;
6. Diseases or factors with clinical abnormalities that need to be excluded, including
but not limited to diseases of the nervous system, cardiovascular system, kidney,
liver, gastrointestinal system, respiratory system, metabolism, bone system and
other systems;
7. Vital signs, physical examination, laboratory examination (such as white blood cell
count less than 3.0*109/L, platelet count less than 75*109/L, TB > 1.5*ULN, ALT >
1*ULN, AST > 1*ULN) and electrocardiogram examination of any items abnormal and
judged by the investigator to be clinically significant;
8. Use of any prescription or over-the-counter drugs within 14 days before
administration;
9. Patients who had received immunosuppressive therapy, cytotoxic therapy or inhaled
corticosteroid therapy within 6 months before administration;
10. A history of drug abuse or use of any drug in the 6 months prior to drug
administration;
11. Pregnant and lactating women;
12. The subject has not taken effective and appropriate contraceptive measures within 30
days before the drug administration;
13. The subjects had sperm and egg donation plans within 3 months after the first drug
administration to the end of the study;
14. Blood donation or massive blood loss (≥200mL), receiving blood transfusion or using
blood products within 3 months prior to drug administration; Or plan to donate blood
or blood components during the trial;
15. Have participated in other drug clinical trials or device clinical trials, and have
taken test drugs or used test devices within 3 months before drug administration;
16. Subjects may not be able to comply with the protocol to complete the study for other
reasons or the investigator may decide that it is not suitable for participants.
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing, China
Investigator: Dazhi Zhang, M.D.
300595@hospital.cqmu.edu.cn
Dazhi Zhang, M.D.
+86 13452382818
300595@hospital.cqmu.edu.cn
Dazhi Zhang, M.D., Study Chair
The Second Affiliated Hospital of Chongqing Medical University