HealthyPhase 1NCT00046397
Phase I Trial of Smallpox Vaccine
A Phase 1 study testing Modified Vaccinia Virus Ankara TBC-M in people with Healthy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will test the safety of an experimental vaccine called Modified Vaccinia Virus Ankara (MVA) for use against the smallpox virus. It will also investigate how many injections of MVA are needed to produce immunity against vaccinia virus, which is closely related to the smallpox virus. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Modified Vaccinia Virus Ankara TBC-M
- Type of treatment
- Vaccines
- How many people
- 195 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2002to Aug 2005
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- A participant must meet all of the inclusion criteria, as follows:
- Age: at least 18 years and birth year no earlier than 1964.
- Available for follow-up for the duration of the study (maximum of 28 weeks; varies according to schedule).
- Able and willing to sign the informed consent form.
- Willing to have blood samples that will be stored for future research.
- In good general health, without clinically significant medical history, physical examination findings or laboratory results.
Show all 23Show fewer
- Hematocrit greater than or equal to 34 percent for women; greater than or equal to 38 percent for men.
- White cell count within institutional normal limits.
- Differential either within institutional normal range or accompanied by site physician approval.
- Total lymphocyte count greater than of equal to 1000 cells/mm3.
- Absolute CD4 count greater than or equal to 400 cells/mm3.
- Platelets within institutional normal limits.
- ALT (SGPT) less than or equal to institutional upper normal limit.
- Serum creatinine less than or equal to 1.3 mg/dL and calculated creatinine clearance (CrCl) greater than or equal to 55 mL/min using the formula below:
- Male CrCl (mL/min) \&eq; 140 - age (yrs)] x [body wt (kg)] divided by 72 x [serum Cr (mg/dL)]
- Female CrCl (mL/min) \&eq; [140 - age (yrs)] x [body wt (kg) x 0.85] divided by 72 x [serum Cr (mg/dL)]
- Normal urinalysis defined as: negative glucose, negative or trace protein, and negative or trace hemoglobin.
- Negative hepatitis B surface antigen (HBsAg).
- Negative anti-HCV or negative HCV PCR if the anti-HCV is positive.
- Negative HIV ELISA and HIV PCR (volunteers who have previously participated in an HIV vaccine study are eligible with positive ELISA if western blot is indeterminate or negative and HIV PCR is negative).
- Negative Beta-HCG serum pregnancy test for women presumed to be of reproductive potential.
- A female participant must meet one of the following criteria: a) no reproductive potential due to menopause (one year without menses), hysterectomy, bilateral oophorectomy, or tubal ligation; b) agrees to consistently practice contraception at least 30 days prior to enrollment and throughout the duration of the study by means of IUD, hormone-based therapy (e.g., contraceptive pills, Norplant or Depo-Provera or other FDA-licensed methods).
- Able to provide proof of identity to the acceptance of the study clinician completing the enrollment process.
Who cannot join
- Volunteers are excluded from study participation if one or more of the following criteria applies:
- Prior vaccination with any vaccinia product.
- Diseases or conditions that cause immunodeficiency (examples are HIV AIDS, leukemia, lymphoma, generalized malignancy, agammaglobulinemia, history of transplantation, or therapy with alkylating agents, antimetabolites, radiation, or oral or parenteral corticosteroids).
- In close physical contact (household or at work) with an individual who has the diseases or conditions that cause immunodeficiency.
- History of eczema, even if the condition is mild or not presently active.
- In close physical contact (household or at work) with an individual who has eczema even if mild or not presently active.
Show all 33Show fewer
- Acute or chronic skin conditions such as atopic dermatitis, burns, impetigo, or varicella zoster (shingles).
- Household member who is pregnant.
- Women who are breast-feeding.
- Household member less than 1 year old or work with children less than 1 year old.
- Serious, life-threatening allergies to antibiotics polymixin B, streptomycin, tetracycline, neomycin, or cidofovir.
- Allergy to eggs or blood products (including immunoglobulin products) or hypersensitivity to probenicid or sulfa-containing medications.
- Receipt of live attenuated viruses within 30 days prior to enrollment.
- Receipt of subunit or killed vaccines within 14 days prior to enrollment.
- Use of investigational research agents within 30 days prior to enrollment.
- Receipt of blood products within 120 days prior to HIV screening.
- Receipt of immunoglobulin within 60 days prior to HIV screening.
- History of serious adverse reactions to vaccines such as anaphylaxis or related symptoms such as hives, respiratory difficulty, angioedema and abdominal pain.
- History of type I or type II diabetes mellitus except gestational diabetes or diabetes controlled with diet alone.
- Participant currently taking anti-TB prophylaxis or therapy.
- History of seizure disorder other than: 1) febrile seizures under the age of two, or 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure more than 3 years ago.
- Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy, or platelet disorder that requires special precautions).
- Splenectomy
- Hypertension that is not well controlled by medication or is more than 150/100 at enrollment.
- Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well-controlled on medication within the past two years; disorder requiring lithium; suicidal ideation within the five years prior to enrollment.
- Any medical, psychiatric, social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent.
- History of military service 1989 or earlier.
- History of cardiomyopathy, myocardial infarction, angina, congestive heart failure, coronary artery disease, stroke, transient ischemic attack or history of 3 or more risk factors for coronary heart disease from the following list:
- current cigarette smoking;
- high blood pressure diagnosed by a doctor;
- high blood cholesterol diagnosed by a doctor;
- diabetes diagnosed by a doctor;
- a first degree relative (father, mother, brother, sister) who had coronary artery disease before the age of 50.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: A Phase I/II Clinical Trial of Modified Vaccinia Virus Ankara (MVA) to Evaluate Its Safety, Dosing Schedule, Immunogenicity and Protective Efficacy Against Dryvax Challenge in Vaccinia-Naive Individuals
This study will test the safety of an experimental vaccine called Modified Vaccinia Virus Ankara (MVA) for use against the smallpox virus. It will also investigate how many injections of MVA are needed to produce immunity against vaccinia virus, which is closely related to the smallpox virus. An effective smallpox vaccine exists, but it can cause side effects that, on rare occasions, can be life-threatening. The FDA gave new license approval for Dryvax on 10/25/02, but has not been used in the general population since smallpox was eradicated worldwide. Both the MVA and Dryvax® (Registered Trademark) vaccines are made using the vaccinia virus, however the MVA vaccine contains a more attenuated, or weakened, form of the virus. [http://www.fda.gov/cber/products/smalwye102502.htm]
Healthy normal volunteers between 18 and 30 years of age, who have never been vaccinated with a smallpox vaccine, may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests, including an HIV test and a pregnancy test for women of childbearing potential.
Read more
MVA, placebo and Dryvax® (Registered Trademark) will be administered by different methods. The MVA vaccine and placebo are injected into an arm muscle with a needle and syringe. The Dryvax® (Registered Trademark) vaccine is administered, as it was for many years, with a special forked needle that is poked lightly into the skin of the upper arm, usually 15 times, in a process called scarification. When the vaccine works, a small pus-filled blister forms, followed by a scab and then scarring at the site of the vaccination. The formation of the blister and scab is called a take, indicating that the vaccine is effective and is evidence of the development of immunity. The development of a take suggests that an individual will be protected against smallpox for at least a few years. If scarification does not take, it can either mean that the person already has immunity or that the vaccine did not work.
Participants will be assigned to groups, as well as, product randomly. For instance, the first study participant could be enrolled into group 3. The Dryvax® (Registered Trademark) dose is given as a challenge to see if the person has a take. A reduced take response or no take, could suggest that MVA is able to produce an immune response. The dosing schedules vary from 12 to 24 weeks and volunteers are in the study a total of 24 to 36 weeks, depending on the number of injections.
Participants will be observed for at least 1 hour after each injection. They will come to the clinic a week after MVA or placebo injections and at least twice a week after Dryvax® (Registered Trademark) for about 21 days to have the injection site evaluated and photographed. At each visit, participants will be asked about how they are feeling and if they are taking any medications. Blood and urine tests will be done on injection days and at follow up visits scheduled 1 and 4 weeks after each immunization as well as 12 weeks after the Dryvax® (Registered Trademark) challenge dose. Additional tests may be done between visits if medically necessary.
Read the detailed description
Phase I/II, randomized, placebo-controlled, double-blinded, schedule finding study of MVA. The hypothesis is that MVA will be safe in humans when administered by intramuscular (IM) injection and will result in an immune response comparable to that observed after Dryvax primary vaccination. The primary objectives include: evaluating the safety of MVA administered by intramuscular (IM) injection on single and multidose schedules and identifying a schedule of MVA that provides clinical evidence of protection against vaccinia (Dryvax) challenge. The secondary objectives are to compare the immunogenicity of Dryvax and MVA as measured by vaccinia-specific neutralizing antibody, ELISA, and intracellular cytokines assays and by a variola-specific neutralizing antibody assay that will be conducted at the CDC on a subset of samples.
- Conditions
- Healthy
- Being tested
- Modified Vaccinia Virus Ankara TBC-M
- Keywords
- Smallpox, Vaccine, Vaccination, Variola, Adults, Smallpox Vaccine, Healthy Volunteer, Small Pox
- Medical subject headings
- Smallpox
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified Vaccinia Virus Ankara TBC-MDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2002 (estimated)
- Study startSep 2002
- Study completionAug 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 195 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00046397
- Sponsor's protocol ID
- 020316
- Other IDs
- 02-I-0316
- Status last verified
- Aug 2005
- First submitted
- 27 Sep 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Stittelaar KJ, Osterhaus AD. MVA: a cuckoo in the vaccine nest? Vaccine. 2001 Jun 14;19(27):V-VI. doi: 10.1016/s0264-410x(01)00171-2. No abstract available.
PubMed 11395217Henderson DA, Inglesby TV, Bartlett JG, Ascher MS, Eitzen E, Jahrling PB, Hauer J, Layton M, McDade J, Osterholm MT, O'Toole T, Parker G, Perl T, Russell PK, Tonat K. Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 1999 Jun 9;281(22):2127-37. doi: 10.1001/jama.281.22.2127.
PubMed 10367824Henderson DA. The looming threat of bioterrorism. Science. 1999 Feb 26;283(5406):1279-82. doi: 10.1126/science.283.5406.1279.
PubMed 10037590
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Trial of Modified Vaccinia Virus Ankara (MVA) to Evaluate Its Safety, Dosing Schedule, Immunogenicity and Protective Efficacy Against Dryvax Challenge in Vaccinia-Naive Individuals
- ClinicalTrials.gov ID
- NCT00046397
- Acronym / sponsor ID
- 020316
- Conditions
- Healthy
- Keywords
- Smallpox, Vaccine, Vaccination, Variola, Adults, Smallpox Vaccine, Healthy Volunteer, Small Pox
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 195 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Sep 2002
- Study completion
- Aug 2005
- First posted
- 30 Sep 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the safety of an experimental vaccine called Modified Vaccinia Virus Ankara (MVA) for use against the smallpox virus. It will also investigate how many injections of MVA are needed to produce immunity against vaccinia virus, which is closely related to the smallpox virus. An effective smallpox vaccine exists, but it can cause side effects that, on rare occasions, can be life-threatening. The FDA gave new license approval for Dryvax on 10/25/02, but has not been used in the general population since smallpox was eradicated worldwide. Both the MVA and Dryvax® (Registered Trademark) vaccines are made using the vaccinia virus, however the MVA vaccine contains a more attenuated, or weakened, form of the virus. [http://www.fda.gov/cber/products/smalwye102502.htm]
Healthy normal volunteers between 18 and 30 years of age, who have never been vaccinated with a smallpox vaccine, may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests, including an HIV test and a pregnancy test for women of childbearing potential.
MVA, placebo and Dryvax® (Registered Trademark) will be administered by different methods. The MVA vaccine and placebo are injected into an arm muscle with a needle and syringe. The Dryvax® (Registered Trademark) vaccine is administered, as it was for many years, with a special forked needle that is poked lightly into the skin of the upper arm, usually 15 times, in a process called scarification. When the vaccine works, a small pus-filled blister forms, followed by a scab and then scarring at the site of the vaccination. The formation of the blister and scab is called a take, indicating that the vaccine is effective and is evidence of the development of immunity. The development of a take suggests that an individual will be protected against smallpox for at least a few years. If scarification does not take, it can either mean that the person already has immunity or that the vaccine did not work.
Participants will be assigned to groups, as well as, product randomly. For instance, the first study participant could be enrolled into group 3. The Dryvax® (Registered Trademark) dose is given as a challenge to see if the person has a take. A reduced take response or no take, could suggest that MVA is able to produce an immune response. The dosing schedules vary from 12 to 24 weeks and volunteers are in the study a total of 24 to 36 weeks, depending on the number of injections.
Participants will be observed for at least 1 hour after each injection. They will come to the clinic a week after MVA or placebo injections and at least twice a week after Dryvax® (Registered Trademark) for about 21 days to have the injection site evaluated and photographed. At each visit, participants will be asked about how they are feeling and if they are taking any medications. Blood and urine tests will be done on injection days and at follow up visits scheduled 1 and 4 weeks after each immunization as well as 12 weeks after the Dryvax® (Registered Trademark) challenge dose. Additional tests may be done between visits if medically necessary.
Detailed description
Phase I/II, randomized, placebo-controlled, double-blinded, schedule finding study of MVA. The hypothesis is that MVA will be safe in humans when administered by intramuscular (IM) injection and will result in an immune response comparable to that observed after Dryvax primary vaccination. The primary objectives include: evaluating the safety of MVA administered by intramuscular (IM) injection on single and multidose schedules and identifying a schedule of MVA that provides clinical evidence of protection against vaccinia (Dryvax) challenge. The secondary objectives are to compare the immunogenicity of Dryvax and MVA as measured by vaccinia-specific neutralizing antibody, ELISA, and intracellular cytokines assays and by a variola-specific neutralizing antibody assay that will be conducted at the CDC on a subset of samples.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- Age: at least 18 years and birth year no earlier than 1964.
- Available for follow-up for the duration of the study (maximum of 28 weeks; varies according to schedule).
- Able and willing to sign the informed consent form.
- Willing to have blood samples that will be stored for future research.
- In good general health, without clinically significant medical history, physical examination findings or laboratory results.
Key exclusion criteria (33 listed)
- Volunteers are excluded from study participation if one or more of the following criteria applies:
- Prior vaccination with any vaccinia product.
- Diseases or conditions that cause immunodeficiency (examples are HIV AIDS, leukemia, lymphoma, generalized malignancy, agammaglobulinemia, history of transplantation, or therapy with alkylating agents, antimetabolites, radiation, or oral or parenteral corticosteroids).
- In close physical contact (household or at work) with an individual who has the diseases or conditions that cause immunodeficiency.
- History of eczema, even if the condition is mild or not presently active.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modified Vaccinia Virus Ankara TBC-M | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 11395217Stittelaar KJ, Osterhaus AD. MVA: a cuckoo in the vaccine nest? Vaccine. 2001 Jun 14;19(27):V-VI. doi: 10.1016/s0264-410x(01)00171-2. No abstract available.
- Background: PubMed 10367824Henderson DA, Inglesby TV, Bartlett JG, Ascher MS, Eitzen E, Jahrling PB, Hauer J, Layton M, McDade J, Osterholm MT, O'Toole T, Parker G, Perl T, Russell PK, Tonat K. Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 1999 Jun 9;281(22):2127-37. doi: 10.1001/jama.281.22.2127.
- Background: PubMed 10037590Henderson DA. The looming threat of bioterrorism. Science. 1999 Feb 26;283(5406):1279-82. doi: 10.1126/science.283.5406.1279.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Modified Vaccinia Virus Ankara TBC-M in people with Healthy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00046397, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.