ACAM 3000 MVA at Harvard Medical School
ACAM 3000 MVA (Acambis Modified Vaccinia Ankara) Immunization Followed by Dryvax® Vaccination of Healthy Vaccinia-Naïve Adults: A Phase I/II, Placebo-Controlled Study of the Effects of Dose and Route of Administration of MVA on Safety, Reactogenicity and Immunogenicity, Followed by Dryvax® Immunization to Assess Effects of MVA Vaccination on Dryvax® Takes
2 other identifiers
interventional
72
1 country
1
Brief Summary
The purpose of this study is to assess the safety of an experimental smallpox vaccine (MVA: Modified Vaccinia Ankara) and to compare the body's immune (system that fights disease) response to this vaccine. Participants will be assigned to 1 of 6 study groups. Each group will include 12 subjects, 10 will receive the modified smallpox vaccine and two will receive placebo, an inactive substance. The vaccine will be administered in 1 of 3 ways: under the skin; in the muscle; or between the muscle and the skin. Groups A and B will receive Dryvax® 6-15 months after the initial MVA vaccine; groups C, D, E, and F will receive Dryvax® 6 months after the initial MVA vaccine. Study procedures will include documenting side effects for 14 days after each vaccination, electrocardiogram (picture of the hearts activity) and blood samples. Participants will be involved in study related procedures for up to 18 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2005
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 19, 2005
CompletedFirst Posted
Study publicly available on registry
August 23, 2005
CompletedStudy Start
First participant enrolled
October 1, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2008
CompletedResults Posted
Study results publicly available
July 8, 2009
CompletedJanuary 5, 2015
September 1, 2009
2.5 years
August 19, 2005
March 26, 2009
December 11, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
Number of Participants Reporting Moderate or Greater Solicited Local Reactions
Number of participants reporting moderate or greater local reactions solicited on the memory aid as well as by study personnel at follow up visits after either vaccination. Participants are counted only once but may have experienced symptoms on multiple occasions.
15 days after vaccination
Number of Participants Reporting Moderate or Greater Solicited Systemic Reactions
Number of participants reporting moderate or greater systemic reactions solicited on the memory aid as well as by study personnel at follow up visits after either vaccination. Participants are counted only once but may have experienced symptoms on multiple occasions.
15 days after vaccination
Number of Participants With Hematologic Laboratory Abnormalities After Vaccination
Number of participants with hematologic laboratory abnormalities after vaccination, including hemoglobin, white blood cell count, neutrophil count and platelet count. Participants are counted only once for each parameter but may have experienced an abnormality of that parameter on multiple occasions.
28 days after vaccination
Number of Participants With Clinical Chemistry Laboratory Abnormalities After Vaccination
Number of participants with clinical chemistry laboratory abnormalities after vaccination, including total bilirubin and serum creatinine. Participants are counted only once for each parameter but may have experienced an abnormality of that parameter on multiple occasions.
28 days after vaccination
Number of Participants With Enzymatic Clinical Laboratory Abnormalities After Vaccination
Number of participants with enzymatic clinical laboratory abnormalities after vaccination, including AST, ALT and alkaline phosphatase. Participants are counted only once for each parameter but may have experienced an abnormality of that parameter on multiple occasions
28 days after vaccination
Number of Participants With Urinalysis Laboratory Abnormalies After Vaccination
Number of participants with urinalysis laboratory abnormalies after vaccination, including proteinuria and hematuria by dipstick. Participants are counted only once for each parameter but may have experienced an abnormality of that parameter on multiple occasions.
28 days after vaccination
Number of Participants With Signs of Possible Myopericarditis
Number of participants with signs of possible myopericarditis, either by clinical or laboratory (EKG, troponin) evaluation, at any time after vaccination for the during of the study
Within 360 days after vaccination
Secondary Outcomes (7)
Peak Neutralizing Antibodies to ACAM3000 MVA
Approximately Day 42 after first vaccination
Peak Neutralizing Antibodies to Vaccinia
Approximately Day 42 after first vaccination
Peak Binding Antibodies (ELISA) to ACAM3000 MVA
Approximately Day 42 after first vaccination
Peak Binding Antibodies (ELISA) to Vaccinia
Approximately Day 42 after first vaccination
Peak T-cell Gamma Interferon Responses (ELISPOT)
Approximately Day 42 after first vaccination
- +2 more secondary outcomes
Study Arms (6)
Group E: ACAM3000 MVA 10^7 ID
EXPERIMENTAL10 subjects to receive ACAM3000 MVA dose 10\^7 TCID50 via intradermal route on days 0 and 28; 2 subjects to receive placebo via intradermal route on days 0 and 28. Dryvax® smallpox vaccine administered at approximately day 180, dosage 10\^8 pfu/ml.
Group F: ACAM3000 MVA 10^8 IM
EXPERIMENTAL10 subjects to receive ACAM3000 MVA dose 10\^8 TCID50 via intramuscular route on days 0 and 28; 2 subjects to receive placebo via intramuscular route on days 0 and 28. Dryvax® smallpox vaccine administered at approximately day 180, dosage 10\^8 pfu/ml.
Group D: ACAM3000 MVA 10^8 SC
EXPERIMENTAL10 subjects to receive ACAM3000 MVA dose 10\^8 TCID50 via subcutaneous route on days 0 and 28; 2 subjects to receive placebo via subcutaneous route on days 0 and 28. Dryvax® smallpox vaccine administered at approximately day 180, dosage 10\^8 pfu/ml.
Group B: ACAM3000 MVA 10^7 IM
EXPERIMENTAL10 subjects to receive ACAM3000 MVA dose 10\^7 TCID50 via intramuscular route on days 0 and 28; 2 subjects to receive placebo via intramuscular route on days 0 and 28. Dryvax® smallpox vaccine administered at approximately day 180, dosage 10\^8 pfu/ml.
Group A: ACAM3000 MVA 10^6 ID
EXPERIMENTAL10 subjects to receive ACAM3000 MVA dose 10\^6 tissue culture infectious dose 50 (TCID50) via intradermal (ID) route on days 0 and 28; 2 subjects to receive placebo via intradermal route on days 0 and 28. Dryvax® smallpox vaccine administered at approximately day 180, dosage 10\^8 pfu/ml.
Group C: ACAM3000 MVA 10^7 SC
EXPERIMENTAL10 subjects to receive ACAM3000 MVA dose 10\^7 TCID50 via subcutaneous (SC) route on days 0 and 28; 2 subjects to receive placebo via subcutaneous route on days 0 and 28. Dryvax® smallpox vaccine administered at approximately day 180, dosage 10\^8 pfu/ml.
Interventions
MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10\^7 or 10\^8 TCID50 intramuscularly (IM).
Sterile saline (0.9%) volume of 0.5 ml intradermally in the deltoid.
Dryvax® smallpox vaccine administered at approximately day 180, dosage 10\^8 pfu/ml.
Eligibility Criteria
You may qualify if:
- General:
- Age: greater than or equal to 18 and born after 1971.
- Complete a written assessment of understanding prior to enrollment and verbalize understanding of all questions answered incorrectly.
- Informed consent: Be able, willing, and have signed the informed consent form.
- Health: Be in good general health without clinically significant medical history, physical examination findings, or clinically significant abnormal laboratory results. A clinically significant condition or process includes one or more of the following: a) A condition that is chronic or recurring and is life threatening b) A process that would affect the immune response c) A process that would require medication that affects the immune response d) A condition for which repeated injections or blood draws may pose additional risk to the participant e) A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being f) A condition or process in which signs or symptoms could be confused with reactions to vaccine
- Laboratory:
- Willing to have blood samples stored for future smallpox related research.
- Hematology and chemistries within institutional normal limits for age and sex for the following: hemoglobin, white blood cell (WBC)\], serum creatinine, platelets, troponin, alanine aminotransferase (ALT) \[within 1.25 under normal limits (ULN), aspartate aminotransferase (AST) (within 1.25 ULN), alkaline phos (within 1.25 ULN), total bilirubin (within 1.25 ULN).
- Negative for Hepatitis B surface antigen and Hepatitis C virus (HCV) antibodies \[If HCV antibodies are positive, and negative for HCV by polymerase chain reaction (PCR), subject is eligible\]
- Negative FDA-approved human immunodeficiency virus (HIV) blood test within 8 weeks prior to enrollment
- Normal urine dipstick or urinalysis:
- Negative glucose, and
- Negative or trace protein and negative or trace hemoglobin (if trace hemoglobin is present, a urinalysis is required to exclude participants with counts greater than the institutional normal range)
- In addition to meeting ALL of the above criteria, FEMALE participants must meet BOTH of the following criteria:
- Negative serum or urine beta-human chorionic gonadotropin (HCG) pregnancy test performed within 24 hours prior to any vaccination.
- +11 more criteria
You may not qualify if:
- Prior vaccination with a vaccinia product. Determined by clinical evidence of scarification or self-reported history of vaccinia vaccination (such as in the United States military before 1991 or after 2003).
- Immunosuppressive medications within 168 days prior to initial study vaccine administration, e.g., oral/parenteral corticosteroids, and/or cytotoxic medications. Not excluded: A participant using any of the following is not excluded: corticosteroid nasal spray for allergic rhinitis; or topical corticosteroids as prescribed by a physician for an acute, uncomplicated dermatitis; or over the counter medications (including topical corticosteroids for an acute, uncomplicated dermatitis); use of rapidly tapered steroids for an acute isolated condition, which does not include asthma within 28 days prior to vaccine administration.
- Currently using corticosteroid eye drops.
- Receipt of blood products within 120 days prior to initial study vaccine administration.
- Receipt of immunoglobulin within 60 days prior to initial study vaccine administration.
- Receipt of live attenuated vaccines within 30 days prior to initial study vaccine administration.
- Receipt of investigational research agents within 30 days prior to initial study vaccine administration.
- Receipt of medically indicated subunit or killed vaccines, e.g., influenza, pneumococcal, or allergy treatment with antigen injections within 14 days prior to initial study vaccine administration.
- Participant has a history of any of the following:
- Acute febrile illness on the day of vaccination.
- Eczema or atopic dermatitis (past or present).
- Chronic exfoliative skin condition.
- Acute skin disorders of large magnitude (greater than 2x2 centimeters), e.g., burns or lacerations.
- History or presence of skin cancer at vaccination site.
- Heart disease including history of a myocardial infarction (MI), angina, congestive heart failure (CHF), or pericardial pathology.
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Brigham and Women's Hospital - Infectious Diseases
Boston, Massachusetts, 02115, United States
Related Publications (2)
Seaman MS, Wilck MB, Baden LR, Walsh SR, Grandpre LE, Devoy C, Giri A, Noble LC, Kleinjan JA, Stevenson KE, Kim HT, Dolin R. Effect of vaccination with modified vaccinia Ankara (ACAM3000) on subsequent challenge with Dryvax. J Infect Dis. 2010 May 1;201(9):1353-60. doi: 10.1086/651560.
PMID: 20350190RESULTWilck MB, Seaman MS, Baden LR, Walsh SR, Grandpre LE, Devoy C, Giri A, Kleinjan JA, Noble LC, Stevenson KE, Kim HT, Dolin R. Safety and immunogenicity of modified vaccinia Ankara (ACAM3000): effect of dose and route of administration. J Infect Dis. 2010 May 1;201(9):1361-70. doi: 10.1086/651561.
PMID: 20350191RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The Dryvax challenge was optional and administered to only a subset of participants before being discontinued prior to being offered to the subjects in the last cohort.
Results Point of Contact
- Title
- Lindsey R. Baden, M.D.
- Organization
- Brigham and Women's Hospital
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 19, 2005
First Posted
August 23, 2005
Study Start
October 1, 2005
Primary Completion
April 1, 2008
Study Completion
April 1, 2008
Last Updated
January 5, 2015
Results First Posted
July 8, 2009
Record last verified: 2009-09