A Study to Assess Dose-Response, Efficacy (Immunogenicity) and the Safety of GC1109

Study Overview
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Brief Summary
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The purpose of this study is to Assess Dose-Response, Efficacy (Immunogenicity) and the Safety of GC1109 Administered in Multi Intramuscular Doses to Healthy Subjects.

Detailed Description
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Step 1 Primary objective Investigate the optimum volume of GC1109 to compare the subject ratio after seroconversion in each Anti-PA Ab by TNA at 4 weeks following infuse the drug 3 times with the immunogenicity of each treatment (GC1109 and placebo cohort) in healthy adults. In healthy adults, three times the clinical dose of about four weeks, compare immunogenicity of each treatment group (GC1109 group and the placebo group) with subsects ratio who have been Seroconversion for Anti-PA Ab by TNA Secondary objective Percentage of subjects after seroconversion in each anti-PA IgG level (by ELISA) at 4 weeks following infuse the drug 3 times in healthy adults Check the Seroprotection antibody titer (survival rate : 50%) with passive immune (nonclinical tests) at 4 weeks following infuse the drug 3 times in healthy adults Establish the Seroconversion rate from the percentage of subjects after seroconversion at 4 weeks following infuse the drug 3 times and seroprotection antibody titer in healthy adults Compare the immunogenicity of each treatment with the GMT's assessment of Anti-PA Ab by TNA for 4 weeks following infuse the drug 3 times Compare the immunogenicity of each treatment with the GMT's assessment of Anti-PA IgG by ELISA for 4 weeks following infuse the drug 3 times Determine the safety of the each treatment cohort Step 2 Primary objective • Evaluate whether the Toxin Neutralization Antibody by TNA assay satisfy the NF50 standard or not at 4 weeks following infuse the optimal dose of GC1109 4 times in healthy adults. Secondary objective Establish the safety of the GC1109 in healthy adults Establish the GMT of Toxin Neutralization Antibody by TNA assay after infusing the drug 4 times until 24 weeks in healthy adults Establish the GMT of Anti-PA IgG by ELISA after infusing the drug 4 times until 24 weeks in healthy adults

Official Title
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A Phase 2 Study to Assess Dose-Response, Efficacy (Immunogenicity) and the Safety of GC1109 Administered in Multi Intramuscular Doses to Healthy Subjects

Conditions
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Anthrax

Intervention / Treatment
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* Biological: GC1109 or Placebo of GC1109


Participation Criteria
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Eligibility Criteria
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Step1 Inclusion Criteria: Healthy 18 to 55 year-olds of either sex Body mass index above 18.5kg/m2 or below 30kg/m2 at the screening time A medical history without clinically significant congenital or chronic disease at the screening test before administrating the study drug within 28 days Agreement to avoid pregnancy or use contraceptive measure between 1 week prior to first dose and the 4 weeks following the final administration Female subjects of childbearing age, have negative serum β-HCG prior to infuse the study drug within 7 days and urine test at the every pre-vaccine Signed, informed voluntarily consents the clinical trials Willingness and agreement to comply with the constraints of the study protocol and ability to understand the study Willingness and ability to return for all follow-up visits and blood draws for the duration of the study Subjects who can have the study vaccine administered into the deltoid muscle and don't have the tattoo Agreement to stop drinking for 7days following the administration of the each study vaccine Agreement not to donate the blood for 24 hours following the administration of the each study vaccine Exclusion Criteria: Prior history of, or known exposure to any form of B.anthracis or any anthrax immunization Employment in an industry involved in contact with ruminant animals, slaughterhose workers, handle the animal raw hides or raw wool, veterinary sciences involving ruminant animals, suspect exposure to any form of B. or anthrax immunization producer and developer. HIV positive or syphilis HAV, HBV, HCV positive or suspect Clinically significant out-of-range of laboratory tests at screening including : hypernatremia, hyponatremia, hypopotassemia, hyperchloremia, hypoproteinemia Prior history of, immunodeficiency or clinically active autoimmune disease Subjects with a history of Guillain-Barre syndrome Subjects with hemophilia or being treated with an anticoagulant who are at increased risk of serious bleeding during intramuscular injection History or evidence of metastatic malignancy tumor for internal organs, blood or flesh Medical significant hypersensitivity or idiosyncratic reaction related to any medical product including study drug or with a history of anaphylaxis Subjects who have had an acute fever exceeding a body temperature of 38.0℃ within 72 hours prior to the administration of the study vaccine, or who have had a symptom suspicious for acute febrile disease within 14 days prior to the administration of the study vaccine. Individuals who have received or intend to receive medication within 30 days of injection of the any experimental drug Donation of blood within 30 days prior to administrate the study drug Subjects who have received or are scheduled for the treatment with the following drug within 120 days (except for inhaled, nasal or topical corticosteroid) Subjects who have received or are scheduled for the treatment with the following drug within 120 days (except for inhaled, nasal or topical corticosteroid) Systemic immunosuppressant therapy, radiotherapy, a high dose of steroid at the similar dose level Blood-derived products including immunoglobulin Systemic immunosuppressant therapy, radiotherapy, a high dose of steroid at the similar dose level Blood-derived products including immunoglobulin Subjects who have received or are scheduled for the treatment with the following drug within the specified period Pre-injection of the IP within 30 days: oriental medicine Pre-injection of the IP within 7 days: ethical the counter drug (ETC), over the counter History or suspect of drug abuse (Amphetamine, barbiturates, cocaine, opioids, benzodiazepines etc) Subject without safety for the administration of vaccine, who in the investigator's opinion are unsuitable for the study or disturb the assessment of clinical trials Step2 Inclusion Criteria: Healthy 19 to 65 year-olds of either sex A medical history without clinically significant congenital or chronic disease at the screening test before administrating the study drug within 28 days. For woman of childbearing age who have not undergone sterilization operation and woman who have not been more than 12 months after menopause, those who agree to avoid pregnancy or use appropriate contraceptive measure for the duration of the study from within one week prior to the first clinical drug administration. Man, who agree to avoid pregnancy or use contraceptive measure for the duration of the study Female subjects of childbearing age, have negative in pregnancy test at the screening visit Signed, informed voluntarily consents the clinical trials Subjects who can have the study drug administered into the deltoid muscle and don't have the tattoo Agreement not to donate the blood for the duration of the study Exclusion Criteria: Prior history of, or known exposure to any form of B. anthracis or any anthrax immunization Employees in an industry involved in contact with ruminant animals(slaughterhouse workers, handle the animal raw hides or raw wool, veterinary sciences involving ruminant animals, suspect exposure to any form of B. or anthrax), immunization producer and developer. HIV positive or suspect HAV, HBV, HCV positive or suspect Prior history of, immunodeficiency or clinically active autoimmune disease Subjects with a history of Guillain-Barre syndrome Subjects with hemophilia or being treated with an anticoagulant who are at increased risk of serious bleeding during intramuscular injection History or evidence of metastatic malignancy tumor for internal organs, blood or flesh Medical significant hypersensitivity, idiosyncratic reaction related to any medical product included in study drug or with a history of anaphylaxis Subjects who have had an acute fever exceeding a body temperature of 38.0℃ within 72 hours prior to the administration of the study vaccine, or who have had a symptom suspicious for acute febrile disease within 14 days prior to the administration of the study drug. A person who has received a split vaccine, inactivated vaccine, or actived vaccine within four weeks prior to administration of a study drug Subjects who have received or are scheduled for the treatment with the following drug within 120 days (except for inhaled, nasal or topical corticosteroid) Systemic immunosuppressant therapy, radiotherapy, a high dose of steroid at the similar dose level Blood-derived products including immunoglobulin A person who has a history of drug abuse within 6 months prior to the administration of a study drug or suspected of taking drugs for fear of abuse through questionnaire and physical examination Pregnant women and lactating women A person whom the investigator determined unsuitable for the study

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Step 1 (Number of Arms: 4), Step 2 (Number of Arms: 2)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GC1109<br>Step1: GC1109 0.3 mL or 0.5 mL or 0.1mL administered in Multi Intramuscular Doses (3 times) to Healthy Subjects Step2: GC1109 1.0 mL administered in Multi Intramuscular Doses (4 times) to Healthy Subjects | Biological: GC1109 or Placebo of GC1109<br>* Step1: Administer 0.3mL or 0.5mL or 0.1mL or placebo of GC1109 into the deltoid muscle three times every four weeks. Step2: Administer 1.0mL of GC1109 or placebo of GC1109 into the deltoid muscle three times every four weeks, and once after 24 weeks.<br>* Other names: rPA or Placebo;|
| Placebo Comparator: Placebo of GC1109<br>Step1: Placebo of GC1109 0.5mL administered in Multi Intramuscular Doses (3 times) to Healthy Subjects Step2: Placebo of GC1109 1.0 mL administered in Multi Intramuscular Doses (4 times) to Healthy Subjects | Biological: GC1109 or Placebo of GC1109<br>* Step1: Administer 0.3mL or 0.5mL or 0.1mL or placebo of GC1109 into the deltoid muscle three times every four weeks. Step2: Administer 1.0mL of GC1109 or placebo of GC1109 into the deltoid muscle three times every four weeks, and once after 24 weeks.<br>* Other names: rPA or Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Step 1) Investigate the optimum volume of GC1109 | Investigate the optimum volume of GC1109 to compare the subject ratio after seroconversion in each Anti-PA Ab by TNA at 4 weeks following infuse the drug 3 times with the immunogenicity of each treatment (GC1109 and placebo cohort) in healthy adults. | at 4 weeks following infuse the drug 3 times | 
| Step 2) Toxin Neutralization Antibody (by TNA assay) of GC1109 | Percentage of subjects with an 0.56 or higher NF50 by evaluating Toxin Neutralization Antibody (by TNA assay) at 4 weeks following infuse the optimal dose of GC1109 4 times in healthy adults. | at 4 weeks following infuse the drug 4 times | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Step 1) Percentage of subjects after seroconversion | Percentage of subjects after seroconversion in each anti-PA IgG level (by ELISA) at 4 weeks following infuse the drug 3 times in healthy adults | for 4 weeks following infuse the drug 3 times | 
| Step 1) Check the Seroprotection antibody titer | Check the Seroprotection antibody titer with passive immune (nonclinical tests) at 4 weeks following infuse the drug 3 times in healthy adults | for 4 weeks following infuse the drug 3 times | 
| Step 1) Seroconversion rate | Establish the Seroconversion rate from the percentage of subjects after seroconversion at 4 weeks following infuse the drug 3 times and seroprotection antibody titer in healthy adults | for 4 weeks following infuse the drug 3 times | 
| Step 1) Compare the immunogenicity with GMT by TNA | Compare the immunogenicity of each treatment with the GMT's assessment of Anti-PA Ab by TNA for 4 weeks following infuse the drug 3 times | for 4 weeks following infuse the drug 3 times | 
| Step 1) Compare the immunogenicity with the GMT by ELISA | Compare the immunogenicity of each treatment with the GMT's assessment of Anti-PA IgG by ELISA for 4 weeks following infuse the drug 3 times | for 4 weeks following infuse the drug 3 times | 
| Step 1), Step 2) Adverse Events | Adverse events such as subjective and objective symptoms | By 24 weeks following infuse the drug 4 times | 
| Step 2) GMT of Toxin Neutralization Antibody by TNA assay | Establish the GMT of Toxin Neutralization Antibody by TNA assay after infusing the drug 4 times until 24 weeks in healthy adults | By 24 weeks following infuse the drug 4 times | 
| Step 2)GMT of Anti-PA IgG by ELISA | Establish the GMT of Anti-PA IgG by ELISA after infusing the drug 4 times until 24 weeks in healthy adults | By 24 weeks following infuse the drug 4 times | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anthrax vaccine