SmallpoxPhase 2NCT00053495

Effect of Dose, Safety, Tolerability of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination

A Phase 2 study testing Vaccinia virus: ACAM2000 smallpox vaccine and vaccinia virus (calf lymph): Dryvax in people with Smallpox, run by Emergent BioSolutions at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox. Read more about this study

Who is it for?: Ages 18 to 29 yearsHealthy volunteers can take part
Conditions the study is for: Smallpox
What is being tested?: Vaccinia virus: ACAM2000 smallpox vaccine and vaccinia virus (calf lymph): Dryvax
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 353 participants
Where: 4 sitesUnited States
Study dates: Jan 2003to Nov 2003
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 29 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

females must not be pregnant, lactating and must agree to use an effective form of birth control for the 30 days following vaccination or unable to bear children.
agree to be available for the entire study and agree to comply with all requirements.

Who cannot join

military service prior to 1989.
history of previous smallpox vaccination.
children 1 year of age or younger in the household or be in close contact
smallpox vaccination within ten years
known or suspected human immunodeficiency virus (HIV) infection, primary immunodeficiency disorder, leukemia, lymphoma, or current radiation treatment or use of immunosuppressive or anti-neoplastic drugs or have a household member or intimate contact with the conditions listed above.
renal disease

Show all 14Show fewer

current or past history of eczema or a household member or direct contact who has eczema.
known allergy or past allergic reactions to latex gloves or to antibiotics which include neomycin, streptomycin, chlortetracycline, and polymyxin B
known allergy or past allergic reaction to blood products.
known allergy to cidofovir or sulfa-containing drugs.
history of allergic phenomena following smallpox vaccination in the past, including urticaria, erythema multiforme, or Stevens-Johnson syndrome.
transfusion of blood or treatment with any blood product.
current or history of drug or alcohol abuse
inoculation with any other live vaccine or participating in another drug or vaccine trial within 30 days of enrollment.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

PRA International
Lenexa, Kansas, 66219
Orlando Clinical Research Center
Orlando, Florida, 32806
Memorial Hospital of Rhode IslandDivision of Infectious Diseases
Pawtucket, Rhode Island, 02860
Bio-Kinetic Clinical Applications
Springfield, Missouri, 65802

Other trials in United States

About this study

Official title: The Effect of Dose On Safety, Tolerability, and Immunogenicity of ACAM2000 Smallpox Vaccine in Adults Without Previous Smallpox Vaccination

The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox.

Read the detailed description

The objective of this study is to determine the minimum dose of ACAM2000 that is calculated to produce a major cutaneous reaction in at least 90% of a population of healthy adults 18-29 years of age and naïve to smallpox vaccine. Specifically, the objectives of this study are to:

Compare the safety and tolerability of four dose levels of ACAM2000 and a standard dose of Dryvax® in healthy adults 18-29 years of age and naïve to smallpox vaccine. Safety and tolerability will be determined by examination of the local cutaneous reaction, adverse events, physical examinations, vital signs, structured interviews, and laboratory analysis.
Determine the immunogenicity of four dose levels of ACAM2000 and a standard dose of Dryvax® in healthy adults 18-29 years of age by comparing:
the proportion of subjects at each dose level who develop a major cutaneous reaction;
the proportion of subjects in each treatment group who develop neutralizing antibodies, including the fold-increase in antibody titer between Baseline and Day 30 sera; and the geometric mean vaccinia neutralizing antibody titer on Day 30.
Determine the minimum dose of ACAM2000 that is calculated to produce a major cutaneous reaction in at least 90% of a population of healthy adults 18-29 years of age and naïve to smallpox vaccine.

Conditions: Smallpox
Being tested: Vaccinia virus: ACAM2000 smallpox vaccine, vaccinia virus (calf lymph): Dryvax
Keywords: Smallpox
Medical subject headings: Smallpox

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Vaccinia virus: ACAM2000 smallpox vaccineBiological
Group 1 dose: 1.0x10-8th PFU/ml Group 2 dose: 2.0x10-8th PFU/ml Group 3 dose: 1.0x10-7th PFU/ml Group 4 dose: 5.0x10-6th PFU/ml
vaccinia virus (calf lymph): DryvaxBiological
Also called Dryvax®
Group 5 dose: 1.0x10-8th PFU/ml

Study groups in NCT00053495
Study group	Role	What they receive
Group 1: ACAM2000 Dose 1	Experimental	Participants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-8th plaque-forming units (PFU)/mL on Day 0. Receives: Biological: Vaccinia virus: ACAM2000 smallpox vaccine
Group 2: ACAM2000 Dose 2	Experimental	Participants will receive a single dose of ACAM2000 smallpox vaccine, 2.0x10-8th plaque-forming units/mL on Day 0. Receives: Biological: Vaccinia virus: ACAM2000 smallpox vaccine
Group 3: ACAM2000 Dose 3	Experimental	Participants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-7th plaque-forming units/mL on Day 0 Receives: Biological: Vaccinia virus: ACAM2000 smallpox vaccine
Group 4: ACAM2000 Dose 4	Experimental	Participants received a single dose of ACAM2000 smallpox vaccine, 5.0x10-6th plaque-forming units/mL on Day 0 Receives: Biological: Vaccinia virus: ACAM2000 smallpox vaccine
Group 5: Dryvax® Vaccine	Active comparator	Participants will receive a single dose of Dryvax® smallpox vaccine, 1.0x10-8th plaque-forming units/mL on Day 0 Receives: Biological: vaccinia virus (calf lymph): Dryvax

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Reporting Adverse Events of Severe Intensity Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine
The severity of each reported adverse event was classified by the investigator according to the following definitions. None - no symptom; Mild - awareness of sign or symptoms, but easily tolerated; Moderate - discomfort enough to cause interference with usual activity; and Severe - incapacitating with inability to work or perform usual activity.
Measured: Days 0 to 30 post-vaccination
Neutralizing Antibody Response Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.
Measured: Day 30 post-vaccination
Participants With ≥ 4-fold Increase in Plaque-Reduction Neutralization Test (PRNT50) Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.
Measured: Day 30 post-vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2003Nov 2003

First posted31 Jan 2003 (estimated)
Study startJan 2003
Primary completionJun 2003
Study completionNov 2003

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for SmallpoxStudies of the same condition, open and under way.
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 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 353 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00053495
Sponsor's protocol ID: H-400-005
Status last verified: Mar 2024
First submitted: 30 Jan 2003
Last updated: 18 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
Study to Assess the Safety and Immunogenicity of TPOXX® When Administered Orally for 28 Days With JYNNEOS
Smallpox
Active, not recruitingPhase 4
Smallpox Vaccine for Mpox Post-Exposure Prophylaxis: A Cluster RCT
Monkeypox
RecruitingPhase 2
A Randomized Clinical Trial Investigating the Safety, Reactogenicity, and Immunogenicity After Immunization With an mRNA-based Mpox Vaccine Candidate in Africa
Mpox (Monkeypox), Smallpox
Enrolling by invitationObservational study
VA-005 Clinical Outcomes of VIGIV Treatment of Smallpox Vaccination Complications or Vaccinia Infection
Complication of Smallpox Vaccination
Active, not recruitingPhase 3
Phase 3 Infant Safety & Immunogenicity Trial of MVA-BN® in DRC
Mpox (Monkeypox), Vaccination

All Smallpox trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of Dose On Safety, Tolerability, and Immunogenicity of ACAM2000 Smallpox Vaccine in Adults Without Previous Smallpox Vaccination
ClinicalTrials.gov ID: NCT00053495
Acronym / sponsor ID: H-400-005
Conditions: Smallpox
Keywords: Smallpox
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 353 participants (actual)
Lead sponsor: Emergent BioSolutionsIndustry (pharma, biotech, devices)
Study start: Jan 2003
Primary completion: Jun 2003 (actual)
Study completion: Nov 2003 (actual)
First posted: 31 Jan 2003 (estimated)
Results: Posted 11 Feb 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox.

Detailed description

Compare the safety and tolerability of four dose levels of ACAM2000 and a standard dose of Dryvax® in healthy adults 18-29 years of age and naïve to smallpox vaccine. Safety and tolerability will be determined by examination of the local cutaneous reaction, adverse events, physical examinations, vital signs, structured interviews, and laboratory analysis.
Determine the immunogenicity of four dose levels of ACAM2000 and a standard dose of Dryvax® in healthy adults 18-29 years of age by comparing:
the proportion of subjects at each dose level who develop a major cutaneous reaction;
the proportion of subjects in each treatment group who develop neutralizing antibodies, including the fold-increase in antibody titer between Baseline and Day 30 sera; and the geometric mean vaccinia neutralizing antibody titer on Day 30.
Determine the minimum dose of ACAM2000 that is calculated to produce a major cutaneous reaction in at least 90% of a population of healthy adults 18-29 years of age and naïve to smallpox vaccine.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Group 1: ACAM2000 Dose 1	Experimental	Biological: Vaccinia virus: ACAM2000 smallpox vaccineParticipants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-8th plaque-forming units (PFU)/mL on Day 0.
Group 2: ACAM2000 Dose 2	Experimental	Biological: Vaccinia virus: ACAM2000 smallpox vaccineParticipants will receive a single dose of ACAM2000 smallpox vaccine, 2.0x10-8th plaque-forming units/mL on Day 0.
Group 3: ACAM2000 Dose 3	Experimental	Biological: Vaccinia virus: ACAM2000 smallpox vaccineParticipants will receive a single dose of ACAM2000 smallpox vaccine, 1.0x10-7th plaque-forming units/mL on Day 0
Group 4: ACAM2000 Dose 4	Experimental	Biological: Vaccinia virus: ACAM2000 smallpox vaccineParticipants received a single dose of ACAM2000 smallpox vaccine, 5.0x10-6th plaque-forming units/mL on Day 0
Group 5: Dryvax® Vaccine	Active comparator	Biological: vaccinia virus (calf lymph): DryvaxParticipants will receive a single dose of Dryvax® smallpox vaccine, 1.0x10-8th plaque-forming units/mL on Day 0

Who may qualify

Ages: 18 to 29 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (2 listed)

females must not be pregnant, lactating and must agree to use an effective form of birth control for the 30 days following vaccination or unable to bear children.
agree to be available for the entire study and agree to comply with all requirements.

Key exclusion criteria (14 listed)

military service prior to 1989.
history of previous smallpox vaccination.
children 1 year of age or younger in the household or be in close contact
smallpox vaccination within ten years
known or suspected human immunodeficiency virus (HIV) infection, primary immunodeficiency disorder, leukemia, lymphoma, or current radiation treatment or use of immunosuppressive or anti-neoplastic drugs or have a household member or intimate contact with the conditions listed above.

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
Vaccinia virus: ACAM2000 smallpox vaccineGroup 1 dose: 1.0x10-8th PFU/ml Group 2 dose: 2.0x10-8th PFU/ml Group 3 dose: 1.0x10-7th PFU/ml Group 4 dose: 5.0x10-6th PFU/ml	Biological	Group 1: ACAM2000 Dose 1, Group 2: ACAM2000 Dose 2, Group 3: ACAM2000 Dose 3, Group 4: ACAM2000 Dose 4
vaccinia virus (calf lymph): DryvaxAlso: Dryvax®Group 5 dose: 1.0x10-8th PFU/ml	Biological	Group 5: Dryvax® Vaccine

Primary outcome

Number of Participants Reporting Adverse Events of Severe Intensity Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine
Time frame: Days 0 to 30 post-vaccination
The severity of each reported adverse event was classified by the investigator according to the following definitions. None - no symptom; Mild - awareness of sign or symptoms, but easily tolerated; Moderate - discomfort enough to cause interference with usual activity; and Severe - incapacitating with inability to work or perform usual activity.
Neutralizing Antibody Response Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.
Time frame: Day 30 post-vaccination
Participants With ≥ 4-fold Increase in Plaque-Reduction Neutralization Test (PRNT50) Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.
Time frame: Day 30 post-vaccination

Results and safety

Results posted to the registry on 11 Feb 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ACAM2000 Dose 1	51	51
ACAM2000 Dose 2	101	101
ACAM2000 Dose 3	101	101
ACAM2000 Dose 4	51	51
Dryvax® Vaccine	49	49

Primary outcome: Number of Participants Reporting Adverse Events of Severe Intensity Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine

Time frame: Days 0 to 30 post-vaccination. Number. Unit: Participants

Measure	ACAM2000 Dose 1 n = 51	ACAM2000 Dose 2 n = 101	ACAM2000 Dose 3 n = 101	ACAM2000 Dose 4 n = 51	Dryvax® Vaccine n = 49
Lymph Node Pain	2	4	3	4	2
Lymphadenopathy	0	0	0	1	0
Diarrhea Not Otherwise Specified	1	0	0	0	0
Nausea	1	0	0	0	0
Vomiting Not Otherwise Specified	1	0	0	0	0
Injection Site Erythema	1	6	14	11	15
Injection Site Swelling	0	0	1	1	0
Injection Site Pruritus	0	0	1	0	1

Population analysed: Adverse events were assessed in the safety, intent-to-treat population

Primary outcome: Neutralizing Antibody Response Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.

Time frame: Day 30 post-vaccination. Mean (Standard Deviation). Unit: PRNT50 Titers

Measure	ACAM2000 Dose 1 n = 51	ACAM2000 Dose 2 n = 100	ACAM2000 Dose 3 n = 100	ACAM2000 Dose 4 n = 50	Dryvax® Vaccine n = 49
Value	212 (536.4)	278 (581.6)	425 (947.4)	582 (1129.3)	1515 (6019.4)

Population analysed: Neutralizing antibody response titers were evaluated in the antibody evaluable, per-protocol population.

Primary outcome: Participants With ≥ 4-fold Increase in Plaque-Reduction Neutralization Test (PRNT50) Titers Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine.

Time frame: Day 30 post-vaccination. Number. Unit: Participants

Measure	ACAM2000 Dose 1 n = 50	ACAM2000 Dose 2 n = 100	ACAM2000 Dose 3 n = 100	ACAM2000 Dose 4 n = 51	Dryvax® Vaccine n = 49
Value	28	73	84	48	47

Population analysed: Plaque-reduction neutralization test (PRNT50) titers were determined in the antibody evaluable, per-protocol population

Adverse events

Time frame: Adverse events data were collected from the day of vaccination for up to 6 months post-vaccination.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ACAM2000 Dose 1	1 of 51 (2%)	51 of 51 (100%)	Not reported
ACAM2000 Dose 2	1 of 101 (1%)	99 of 101 (98%)	Not reported
ACAM2000 Dose 3	0 of 101 (0%)	98 of 101 (97%)	Not reported
ACAM2000 Dose 4	1 of 51 (2%)	51 of 51 (100%)	Not reported
Dryvax® Vaccine	0 of 49 (0%)	49 of 49 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Smallpox

Active, not recruitingPhase 2
Study to Assess the Safety and Immunogenicity of TPOXX® When Administered Orally for 28 Days With JYNNEOS
Smallpox
Active, not recruitingPhase 4
Smallpox Vaccine for Mpox Post-Exposure Prophylaxis: A Cluster RCT
Monkeypox
RecruitingPhase 2
A Randomized Clinical Trial Investigating the Safety, Reactogenicity, and Immunogenicity After Immunization With an mRNA-based Mpox Vaccine Candidate in Africa
Mpox (Monkeypox), Smallpox
Enrolling by invitationObservational study
VA-005 Clinical Outcomes of VIGIV Treatment of Smallpox Vaccination Complications or Vaccinia Infection
Complication of Smallpox Vaccination
Active, not recruitingPhase 3
Phase 3 Infant Safety & Immunogenicity Trial of MVA-BN® in DRC
Mpox (Monkeypox), Vaccination

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.

Medical Director study director

Emergent BioSolutions

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vaccinia virus: ACAM2000 smallpox vaccine and vaccinia virus (calf lymph): Dryvax in people with Smallpox, run by Emergent BioSolutions at 4 sites 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 2 inclusion and 14 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 18 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Feb 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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.

What does the primary outcome measure?

Number of Participants Reporting Adverse Events of Severe Intensity Post-vaccination With ACAM2000 or Dryvax® Smallpox Vaccine (time frame: Days 0 to 30 post-vaccination). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00053495.

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 18 Mar 2024.