Clinical Trial: Assessment of the Immunogenicity and Safety of a Dose-Sparing BioThrax® AVA Schedule
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Randomized Trial for the Assessment of Immunogenicity and Safety of Four Different Dosing Regimens of BioThrax® for Post-Exposure Prophylaxis for Anthrax in Adults
Brief Summary: A Phase IV, randomized, multicenter trial to assess the immunogenicity and safety of BioThrax® in varying dose regimens with the primary objective of obtaining information on possible dose-sparing strategies in the event of a major biothreat.
Detailed Summary: This is a Phase IV, randomized, open-label immunogenicity and safety study to evaluate four dosing regimens of BioThrax® for Post-Exposure Prophylaxis (PEP) for anthrax. BioThrax® will be administered as a subcutaneous (SC) injection for the primary series and will be administered as an intramuscular (IM) injection for the boost. The four dosing regimens are: 0.50mL BioThrax® on Days 0, 14, and 6 month boost; 0.50mL BioThrax® on Days 0, 28 and 6 month boost; 0.50mL BioThrax® on Days 0, 14, 28 and 6 month boost and 0.25mL BioThrax® on Days 0, 14, and 28, 6 month boost with 0.50ml IM Approximately 300 subjects will be randomized 1:1:1:1 to one of the four study arms. Enrollment will be stratified by gender, with approximately equal numbers of males and females (18 through 65 years) enrolled into each dosing regimen. The Primary objective is to evaluate the immunogenicity of the four dosing regimens of BioThrax® using the Toxin Neutralization Assay (TNA). The secondary objective is to evaluate the safety of the four dosing regimens of BioThrax®.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Current Primary Outcome: Number of Participants With a Four-fold or Greater Increase From Baseline in Toxin Neutralization Antibody Assay (TNA) 50 Percent Neutralization Factor ( NF50 ) Antibody Titer [ Time Frame: Days 0, 7, 14, 21, 28 35, 42, 49, 56, 63, 70, 84 and 100 ]
Original Primary Outcome: The proportion of subjects with a four-fold or greater increase from baseline in toxin neutralization antibody assay (TNA) 50 percent Neutralization Factor ( NF50 ) antibody titer in each study arm [ Time Frame: Days 7, 14, 21, 28 35, 42, 49, 56, 63, 70, 84 and 100. ]
Current Secondary Outcome:
- Geometric Mean Concentration (GMC) of Enzyme-linked Immunosorbent Assay (ELISA) Antibody Against the Protective Antigen (Anti-PA IgG) [ Time Frame: Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. ]Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the ELISA assay to determine the anti-PA IgG antibody concentration. The geometric mean of subjects' visit-specific titers were calculated along with the 95% confidence intervals. If the antibody titer was below the lower limit of quantification (LLOQ) for the assay, half the value of LLOQ (4.64) was imputed. When all subjects' titers were below LLOQ resulting in no variability within the group, the 95% CI was not calculated.
- Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 0 by Maximum Severity [ Time Frame: Days 0-7 after vaccination at Day 0 ]Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days.
- Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 14 by Maximum Severity [ Time Frame: Days 0-7 after vaccination at Day 14 ]Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days.
- Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 28 by Maximum Severity [ Time Frame: Days 0-7 after vaccination at Day 28 ]Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days.
- Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following the 6-month Boost by Maximum Severity [ Time Frame: Days 0-7 after vaccination at Month 6 ]Participants maintained a memory aid to record daily the occurrence of local reactions for 8 days after the 6-month intramuscular boost vaccination based on their interference with daily activities (pain, itchiness, warmth, and tenderness at injection site, arm motion limitation) or based on a quantitative measurement of the reaction (edema, erythema). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions did not interfere with daily activities. For the quantitative scale, severe reactions greater than 100 millimeters (mm), moderate reactions were 51-100 mm, and mild reactions were 25-50 mm. Participants are counted by the maximum severity they reported experiencing the reaction on any of the 8 days.
- Number of Participants With Injection Site Edema and Erythema With a Size of Greater Than 120 Millimeters (mm) [ Time Frame: Days 0-7 after each vaccination ]Participants were given a ruler with the memory aid to measure the occurrence of edema (swelling) and erythema (redness) daily for at least 8 days after each vaccination. Participants are counted in this outcome measure if they had measurements of greater than 120 mm in the 8-day period after at least one vaccination, first separately for edema and
Original Secondary Outcome:
- Immunogenicity: The TNA NF50 GMT antibody titer in each study arm at Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. [ Time Frame: Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. ]
- Immunogenicity: The proportion of subjects with a four-fold or greater increase from baseline in Enzyme-linked Immunosorbent Assay (ELISA) antibody titer against the protective antigen (anti-PA IgG) in each study arm [ Time Frame: Days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. ]
- Immunogenicity: The TNA NF50 peak geometric mean titer (GMT) antibody response in each study arm through Day 100. [ Time Frame: Day 0 through Day 100 ]
- Safety: The incidence of injection site reactogenicity symptoms (edema and erythema) with a size of greater than 120 millimeters (mm) in each study arm [ Time Frame: Days 0-7 after each vaccination ]
- Immunogenicity: The GMC ELISA anti PA IgG antibody titer in each study arm at Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. [ Time Frame: Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100. ]
- Safety: The incidence and severity of injection site reactogenicity symptoms for eight days (Day 0-7) post each vaccination in each study arm [ Time Frame: Days 0-7 after each vaccination ]
- Safety: The incidence and severity of systemic symptoms for eight days (Day 0-7) post each vaccination in each study arm. [ Time Frame: Days 0-7 after each vaccination ]
- Immunogenicity: The peak geometric mean concentration (GMC) ELISA anti-PA IgG antibody titer in each study arm through Day 100. [ Time Frame: Day 0 through Day 100 ]
Information By: National Institute of Allergy and Infectious Diseases (NIAID)
Dates:
Date Received: July 5, 2012
Date Started: July 2012
Date Completion:
Last Updated: April 24, 2014
Last Verified: April 2014
