|
|
|
|
|
|
Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00133575 |
The purpose of this study is to compare the body's immune response to a vaccine against smallpox infection, MVA (modified vaccinia Ankara). 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: intradermal (under the skin of the forearm); intramuscular (in the muscle of the upper arm); or subcutaneous (between the muscle and the skin of the upper arm). All subjects will receive Dryvax vaccine. 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, assessments, electrocardiogram (picture of the hearts activity) and blood samples. Participants will be involved in study related procedures for up to 18 months.
Condition | Intervention | Phase |
Variola Major (Smallpox) |
Biological: ACAM3000 MVA Biological: GMP Grade PBS |
Phase I Phase II |
MedlinePlus related topics: | Smallpox |
Drug Information available for: | Sodium chloride PANVAC-V |
Study Type: | Interventional |
Study Design: | Prevention, Randomized, Double Blind (Subject, Investigator), Dose Comparison, Parallel Assignment, Safety/Efficacy Study |
Official Title: | 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 |
Enrollment: | 72 |
Study Start Date: | October 2005 |
Study Completion Date: | April 2008 |
Primary Completion Date: | April 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
A: Experimental
10 subjects to receive ACAM3000 MVA dose 10^6 TCID50 via intradermal route on days 0 and 28; 2 subjects to receive placebo via intradermal route on days 0 and 28.
|
Biological: ACAM3000 MVA
MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10^6 or 10^7 TCID50 intradermally (ID).
Biological: GMP Grade PBS
Phosphate buffered saline administered intradermally (ID).
|
B: Experimental
10 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.
|
Biological: ACAM3000 MVA
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).
Biological: GMP Grade PBS
Phosphate buffered saline administered intramuscularly (IM).
|
C: Experimental
10 subjects to receive ACAM3000 MVA dose 10^7 TCID50 via subcutaneous route on days 0 and 28; 2 subjects to receive placebo via subcutaneous route on days 0 and 28.
|
Biological: ACAM3000 MVA
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 subcutaneously (SC).
Biological: GMP Grade PBS
Phosphate buffered saline administered subcutaneously (SC).
|
D: Experimental
10 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.
|
Biological: ACAM3000 MVA
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 subcutaneously (SC).
Biological: GMP Grade PBS
Phosphate buffered saline administered subcutaneously (SC).
|
E: Experimental
10 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.
|
Biological: ACAM3000 MVA
MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10^6 or 10^7 TCID50 intradermally (ID).
Biological: GMP Grade PBS
Phosphate buffered saline administered intradermally (ID).
|
F: Experimental
10 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.
|
Biological: ACAM3000 MVA
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).
Biological: GMP Grade PBS
Phosphate buffered saline administered intramuscularly (IM).
|
The emergence of smallpox as a potential agent of bioterrorism has heightened concern about the vulnerability of the population to infection with this agent, and has led to proposals to undertake large scale smallpox immunization of military personnel and "first responders" in the U.S., including certain health care workers. A particularly promising vaccine approach to the development of an effective, yet less reactogenic vaccine to smallpox is the use of Modified Vaccinia Ankara (MVA) as a vaccine. Despite the established efficacy of smallpox vaccination, the parameters of protective immunity against smallpox infection are incompletely understood. This is a phase I trial to be conducted under a placebo controlled, double-blind, randomized allocation of smallpox vaccine. The purpose of this study is to assess the safety and immunogenicity of ACAM 3000 MVA in healthy vaccinia-naïve adult subjects. Participants will include 72 healthy, male or female, from the Boston metropolitan area. Six dose regimens will be studied initially: 10^6 or 10^7 TCID50 administered intradermally and 10^7 or 10^8 TCID50 administered intramuscularly or subcutaneously as 2 immunizations 1 month apart. Each arm will be comprised of 12 subjects, 10 of whom will receive ACAM3000 MVA and 2 of whom will receive placebo. A subsequent vaccinia vaccination will be offered to all patients. Consenting participants will receive a Dryvax vaccination 6-15 months after the first dose of MVA. Assessment of safety will be carried out by observation and measurement of acute clinical and laboratory evidence of toxicity; including clinical, electrocardiographic or laboratory evidence of myopericarditis. Assessment of immunogenicity will be carried out by the measurement of humoral and cell-mediated immune response to ACAM 3000 MVA and vaccinia, performed on blood samples obtained at various times prior to and after immunization over the one year period of the study. Response to vaccinia will be assessed clinically (effect on a "take") and the results will be correlated with immune responses to MVA. The primary outcome will be safety as measured by clinical and laboratory toxicity. The secondary outcome will be immunogenicity as measured by humoral and cell-medicated immune responses to vaccinia and ACAM3000 MVA from blood samples obtained at various time points after immunization. Participants will be involved in study related procedures for up to 18 months.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
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
Normal urine dipstick or urinalysis:
In addition to meeting ALL of the above criteria, FEMALE participants must meet BOTH of the following criteria:
Reproductive status: A female participant either must:
i) condoms (male or female with or without a spermicide) ii) diaphragm or cervical cap with spermicide iii) intrauterine device (IUD) iv) hormone-based therapy, e.g., contraceptive pills, Norplant, or Depo-Provera
In addition to the above criteria, female participants must meet the following criteria prior to participating in Dryvax vaccination:
Comply with one of the following methods of contraception for at least 21 days prior to vaccination and at least 2 months post vaccination.
i) Hysterectomy or tubal ligation ii) The participant is in a monogamous relationship with a male partner who has undergone successful vasectomy (Successful vasectomy as defined as microscopic documentation of azospermia or a vasectomy more than two years ago with no resultant pregnancy despite sexual activity post-vasectomy.) c) Sexual abstinence
Exclusion Criteria:
Participant has a history of any of the following:
NOTE: This criterion applies only to subjects 20 years of age and older AND only if at least one of the following applies:
have a family history of coronary heart disease in male first-degree relative (father or brother) less than 55 years of age or a female first-degree relative (mother or sister) less than 65 years of age.
Individuals with an immunosuppressive disorder such as HIV infection, organ transplantation, or a condition requiring prolonged corticosteroid therapy
-ECG with clinically significant findings, or features that would interfere with the assessment of myo/pericarditis as determined by the consulting cardiologist, including any of the following: (1) Conduction disturbance (complete left or incomplete right bundle branch block or nonspecific intraventricular conduction disturbance with QRS greater than 120 ms, AV block of any degree, or QTc prolongation (greater than 440 ms)); (2) Repolarization (ST segment or T wave) abnormality; (3) Significant atrial or ventricular arrhythmia; (4) Frequent atrial or ventricular ectopy (e.g. frequent premature atrial contractions, 2 premature ventricular contractions in a row); (5) ST elevation consistent with ischemia; (6) Evidence of past or evolving myocardial infarction.
-Known or suspected allergy to any component of the vaccine or diluent.
-Allergy to eggs or blood products (including IgG or vaccinia immunoglobulin).
-Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. Not excluded: A participant who had an adverse reaction to pertussis vaccine as a child is not excluded.
-Autoimmune disease.
-Immunodeficiency.
Inhaled steroids are not permissible -Diabetes mellitus type I or type II including cases controlled with diet alone. Not excluded: A participant with past gestational diabetes is not excluded.
a) Psychoses within the past 5 years. b) Suicidal ideation occurring within 2 years prior to enrollment. Not excluded: A participant with a remote history (greater than 3 years) of a suicide attempt or suicide gesture is not excluded if the investigator finds the participant (a) to be of sound mental health; and (b) the suicide attempt was a well-defined, isolated event; and (c) the cause or inciting factor(s) no longer has relevance to the individual. A participant currently in therapy, due to a suicide attempt or gesture, or suicidal ideation, may be enrolled only when the participant's current therapist or health care provider provides documentation that the participant currently is not suicidal.
In addition to the above criteria, the following exclusion criteria apply to those participants consenting to Dryvax vaccination:
A history of the following:
a) Excessive scarring b) Known or suspected allergy to any component of the vaccine or diluent including polymyxin B sulfate, dihydrostreptomycin sulfate, chlorotetracycline hydrochloride, neomycin, and phenol.
c) Known allergy to cidofovir or probenecid
Abnormal renal function:
i) Males: [(140 - age in years) X weight in Kg]/(72 X serum creatinine) ii) Females: 0.85 X [(140 - age in years) X weight in Kg]/(72 X serum creatinine)
Responsible Party: | HHS/NIAID/DMID ( Robert Johnson ) |
Study ID Numbers: | 05-0010 |
First Received: | August 19, 2005 |
Last Updated: | September 18, 2008 |
ClinicalTrials.gov Identifier: | NCT00133575 |
Health Authority: | United States: Federal Government; United States: Food and Drug Administration; United States: Institutional Review Board |
|
|
|