Safety, Reactogenicity and Immunogenicity of MVA in Hematopoietic Stem Cell Transplant (HSCT) Subjects

NCT00565929 | Completed Phase 1

• 2 other identifiers: 07-00425U54AI057159-10
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare how the body's immune system reacts to a vaccine against smallpox infection, called Modified Vaccinia Ankara (MVA) and to evaluate the safety of this vaccine. Study participants will include 24 adults, ages 18-60 years, who have undergone a stem cell transplant more than 2 years ago. Study procedures will include a physical exam, blood samples, heart activity assessments, and urine samples. Participants will be assigned to 1 of 2 possible study vaccine groups. The participants will receive 1 of 2 possible vaccine doses or placebo (substance containing no medication) 28 days apart. Participants will make at least 8 visits to the clinic during the course of the study; additional visits may be needed if the participant experiences side effects from the vaccine. Participants may be involved in study related procedures for about 6 months.

Conditions

Variola Major (Smallpox)

Keywords

Variola major, smallpox, vaccine, hematopoietic stem cell transplant

Outcome Measures

Primary Outcomes (1)

• Safety: acute reactogenicity, both local and systemic; and hematologic and clinical chemistry laboratory values.

  Day 0-180.

Secondary Outcomes (1)

• Immunogenicity: humoral and cell-mediated immune responses.

  Screening, Days 14 and 28 after 1st vaccination; Days 0, 14, 28, 56, and 152 after 2nd vaccination.

Study Arms (2)

Group A: MVA-BN 1 X 10^7 TCID 50

EXPERIMENTAL

10 participants to receive vaccine dose 1X10\^7 TCID 50; 2 participants to receive placebo.

Drug: Placebo; Biological: MVA-BN

Group B: MVA-BN 1 X 10^8 TCID 50

EXPERIMENTAL

10 participants to receive vaccine dose 1X10\^8 TCID 50; 2 participants to receive placebo.

Drug: Placebo; Biological: MVA-BN

Interventions

Placebo DRUG

Sterile saline (0.9%).

Group A: MVA-BN 1 X 10^7 TCID 50; Group B: MVA-BN 1 X 10^8 TCID 50

MVA-BN BIOLOGICAL

The smallpox vaccine is a liquid frozen solution formulated to contain 0.605 mg Tris and 4.090 mg sodium chloride (NaCl) per 0.5 mL dose. The concentration of the virus will be 1 X 10\^8 tissue culture infectious dose 50 (TCID 50) per 0.5 mL dose and may be diluted in a solution of 0.9% saline prior to vaccination. Smallpox vaccine administered in 2 doses approximately 28 days apart in one of the following doses: 1X10\^7 or 1X10\^8 TCID 50.

Group A: MVA-BN 1 X 10^7 TCID 50; Group B: MVA-BN 1 X 10^8 TCID 50

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General:
• Age: 18 to 60
• 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
• Undergone stem cell transplant more than 2 years prior to enrollment
• Current Health: Be in good general health without evidence of active malignancy and off immunosuppressant medications. Without evidence of 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:
• An active condition that is life threatening
• A condition for which repeated injections or blood draws may pose additional risk to the participant
• A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being
• A condition or process in which signs or symptoms could be confused with reactions to vaccine
• Laboratory:
• Hematology and chemistries: Chemistries within 1.25x of the institutional normal limits for age and sex for alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alkaline Phos, and Total Bilirubin. Creatinine less than or equal to 1.8 mg/dL. Platelets and Troponin I or T must be within normal range. Hemoglobin above 10.5 gm/dL for women and 11.5 gm/dL for men and white blood cells (WBC) between 3,000 and 12,500 cells/mm\^3.
• 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 Food and Drug Administration (FDA)-approved human immunodeficiency virus (HIV) blood test within 8 weeks prior to enrollment
• Normal urine dipstick or urinalysis:

You may not qualify if:

• Chronic Graft versus Host Disease (GVHD) requiring systemic immunosuppressive medication within the last 6 months.
• Immunosuppressive medications within 30 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, excluding asthma which is addressed separately-within 28 days prior to vaccine administration.
• Asthma that is unstable, e.g., use of oral or intravenous corticosteroids, hospitalization or intubation during the past 2 years.
• a. In addition, exclude a participant who routinely uses a moderate to high dose inhaled corticosteroids (e.g., more than equivalent of 264 micrograms (mcg) fluticasone; 600 mcg budesonide; 240 mcg beclomethasone; 1000 mcg flunisolide, 750 mcg triamcinolone or 200 mcg mometasone, as a daily dose).
• 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 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)
• Acute skin disorders of large magnitude (greater than 2x2 cm), e.g., burns or lacerations
• History or presence of skin cancer at vaccination site(s)
• Heart disease including history of a myocardial infarction (MI), angina, congestive heart failure (CHF), or pericardial pathology
• Twenty 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).
• Known allergy to eggs.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Brigham and Women's Hospital - Infectious Diseases

Boston, Massachusetts, 02115-6110, United States

Location

Related Publications (1)

• Walsh SR, Wilck MB, Dominguez DJ, Zablowsky E, Bajimaya S, Gagne LS, Verrill KA, Kleinjan JA, Patel A, Zhang Y, Hill H, Acharyya A, Fisher DC, Antin JH, Seaman MS, Dolin R, Baden LR. Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled trial. J Infect Dis. 2013 Jun 15;207(12):1888-97. doi: 10.1093/infdis/jit105. Epub 2013 Mar 12.

  PMID: 23482644 RESULT

MeSH Terms

Conditions

Smallpox

Interventions

smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

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: November 29, 2007
• First Posted: November 30, 2007
• Study Start: September 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: August 2, 2013

Record last verified: 2012-09

Locations

US (1)