A Phase II Study on Immunogenicity and Safety of MVA-BN®... | NCT00316602

NCT00316602

ID	Type	Description	Link
HHSN266200400072C	Other Grant/Funding Number	NIAID

Status Module

Sponsor/Collaborators Module

Name	Class
National Institute of Allergy and Infectious Diseases (NIAID)	NIH

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Healthy Participants	Experimental	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)	Biological: IMVAMUNE
Atopic Dermatitis Participants	Experimental	Vaccinia naive subjects with diagnosed Atopic Dermatitis. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] <= 30), receiving two doses of MVA-BN (IMVAMUNE)	Biological: IMVAMUNE

Name	Type	Description	Arm Group Labels	Other Names
IMVAMUNE	Biological	Subjects receiving two subcutaneous vaccinations	Atopic Dermatitis Participants Healthy Participants

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Seroconversion by ELISA	Seroconversion rate based on Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.	week 6

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Seroconversion by ELISA	Seroconversion rate based on Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Group 1 (Healthy Participants):

Subjects without present or history of any kind of atopy.

Group 2 (Atopic Dermatitis Participants):

Subjects with diagnosed atopic dermatitis.

All study subjects:

Male and female subjects between 18 and 40 years of age without history of smallpox vaccination.
Women must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination.
Women of childbearing potential must have used an acceptable method of contraception for 30 days prior to the first vaccination, must agree to use an acceptable method of contraception during the study, and must not become pregnant for at least 28 days after the last vaccination.
Lab values without clinically significant findings.
Electrocardiogram (ECG) without clinically significant findings.

Exclusion Criteria:

Pregnant or breast-feeding women.
Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.
Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer at the vaccination site are excluded.
History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure.
History of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years.
Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool: (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof) NOTE: This criterion applies only to volunteers 20 years of age and older.
History of anaphylaxis or severe allergic reaction.
Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.
Administration of immunomodulatory substances.

Contacts/Locations Module

Name	Affiliation	Role
Richard N Greenberg, M.D.	University of Kentucky School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Alta Clinical Research LLC		Tucson	Arizona	85745	United States
Burke Pharmaceutical Research

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26439129	Result	Greenberg RN, Hurley MY, Dinh DV, Mraz S, Vera JG, von Bredow D, von Krempelhuber A, Roesch S, Virgin G, Arndtz-Wiedemann N, Meyer TP, Schmidt D, Nichols R, Young P, Chaplin P. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis. PLoS One. 2015 Oct 6;10(10):e0138348. doi: 10.1371/journal.pone.0138348. eCollection 2015.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE) IMVAMUNE: Subjects receiving two subcutaneous vaccinations
FG001	Atopic Dermatitis Participants

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Vaccinia naive subjects with diagnosed Atopic Dermatitis. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] <= 30), receiving two doses of MVA-BN (IMVAMUNE)

IMVAMUNE: Subjects receiving two subcutaneous vaccinations

Arm/Group Information

ID	Title	Description
BG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
BG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00027.4± 5.81 BG00127.9± 6.33 BG00227.7± 6.11

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000150 BG001223 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Black

Title	Measurements
	BG00024 BG00133 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000194 BG001243 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Seroconversion by ELISA

Seroconversion rate based on Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

Per Protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

week 6

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000194 OG001257

Title

Denominators

Categories

Title	Measurements
	OG00098.5(95.5 to 99.7) OG00197.3(94.5 to 98.9)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Difference in seroconversion rates (%)	-1.2			1-Sided	97.5	-4.3						Non-Inferiority	The non-inferiority margin to show that Group 2 (Atopic Dermatitis Participants) is non-inferior to Group 1 (Healthy Participants) in terms of seroconversion rate at Week 6 was predefined as -5% for the difference in seroconversion rates.

Secondary

Percentage of Participants With Seroconversion by ELISA

Per Protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

within 32 weeks

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

ELISA GMT

Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'.

Per Protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

within 32 weeks

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Seroconversion by PRNT

Seroconversion rate based on Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (15) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.

Per Protocol Set

Posted

Number

95% Confidence Interval

percentage of subjects

within 32 weeks

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

PRNT GMT

Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Titers below the detection limit are included with a value of '1'.

Per Protocol Set

Posted

Geometric Mean

95% Confidence Interval

Titer

within 32 weeks

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

ELISPOT IFN-γ Values

Number of interferon gamma (IFN-γ) secreting peripheral blood mononuclear cells (PBMC) per 10^6 PBMC in response to restimulation with MVA-BN detected by ELISPOT assay

ELISPOT Analysis Set

Posted

Median

Full Range

Spot Forming Units / 10^6 PBMC

within 6 weeks

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

Number of Participants With SAEs

Occurrence, relationship and intensity of any serious AE (SAE)

Safety Analysis Set

Posted

Count of Participants

Participants

within 32 weeks

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

Number of Participants With Related Grade >=3 Adverse Events

Number of Participants with any Grade >=3 Adverse Event probably, possibly, or definitely related to the study vaccine. Pooled solicited (general) and unsolicited AEs.

Safety Analysis Set

Posted

Count of Participants

Participants

within 29 days after vaccination

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

Number of Participants With Solicited Local Adverse Events

Number of Participants with and Intensity of solicited local AEs (erythema, swelling and pain). Percentages based on subjects with at least one completed diary card.

Safety Analysis Set

Posted

Count of Participants

Participants

within 8 days after any vaccination

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

Number of Participants With Solicited General AEs

Number of Participants with solicited systemic/general AEs (elevated body temperature, headache, myalgia, nausea, fatigue and chills): Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card.

Safety Analysis Set

Posted

Count of Participants

Participants

within 8 days after any vaccination

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

Number of Unsolicited Non-serious Adverse Events: Intensity

Occurrence of unsolicited non-serious AEs by Intensity

Safety Analysis Set

Posted

Number

events

within 29 days after any vaccination

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Secondary

Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination

Occurrence of unsolicited non-serious AEs by relationship to study vaccine

Safety Analysis Set

Posted

Number

events

within 29 days after any vaccination

ID	Title	Description
OG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)
OG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Healthy Participants	Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)	0	282	3	282	133	282
EG001	Atopic Dermatitis Participants	Vaccinia naïve subjects with diagnosed AD. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] ≤ 30)	0	350	3	350	196	350

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Extraocular muscle paresis	Eye disorders	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected350 at risk
Head injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected350 at risk
Loss of consciousness	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected350 at risk
Panic attack	Psychiatric disorders	Systematic Assessment	EG0001 events1 affected282 at risk EG0010 events0 affected350 at risk
Neurosis	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected282 at risk EG0012 events1 affected350 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected350 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 events0 affected282 at risk EG0011 events1 affected350 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Injection site pruritus	General disorders	Systematic Assessment	EG00048 affected282 at risk EG001100 affected350 at risk
Injection site bruising	General disorders	Systematic Assessment	EG0002 affected282 at risk EG0017 affected350 at risk
Injection site induration	General disorders	Systematic Assessment	EG0006 affected282 at risk EG0013 affected350 at risk
Troponin I increased	Investigations	Systematic Assessment	EG00037 affected282 at risk EG00154 affected350 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG00011 affected282 at risk EG00123 affected350 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0008 affected282 at risk EG00111 affected350 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0009 affected282 at risk EG0016 affected350 at risk
Pharyngitis	Infections and infestations	Systematic Assessment	EG0009 affected282 at risk EG0014 affected350 at risk
Pharyngotonsillitis	Infections and infestations	Systematic Assessment	EG0007 affected282 at risk EG0013 affected350 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0007 affected282 at risk EG0019 affected350 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00019 affected282 at risk EG00116 affected350 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0007 affected282 at risk EG00111 affected350 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected282 at risk EG00115 affected350 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0008 affected282 at risk EG0013 affected350 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0008 affected282 at risk EG0012 affected350 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0006 affected282 at risk EG0013 affected350 at risk
Dysmenorrhoea	Reproductive system and breast disorders	Systematic Assessment	EG0007 affected282 at risk EG0018 affected350 at risk

ID	Term
D003876	Dermatitis, Atopic
D012899	Smallpox

Ancestor Terms

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D003872	Dermatitis
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D017443	Skin Diseases, Eczematous
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases
D011213	Poxviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections

ID	Term
C527606	smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic