Phase II Trial to Assess Safety and Immunogenicity of IMVAMUNE®

NCT01827371 | Completed Phase 2 Results

• 2 other identifiers: 11-0021HHSN272200800004C
• Study Type: interventional
• Target: 435
• Locations: 1 country
• Sites: 6

Brief Summary

Imvamune (licensed name of MVA being developed as a smallpox vaccine) has been tested in over 2,000 individuals and is on path for licensure. This study will be a Phase II to evaluate three different immunization schedules and two different modes of delivery. The study will look at condensed schedules. Study will randomize subjects to one of four arms.

Conditions

Smallpox

Keywords

Smallpox, vaccine, IMVAMUNE, Stratis, parent protocol

Outcome Measures

Primary Outcomes (2)

• Geometric Mean Peak Plaque Reduction Neutralization Titer (PRNT) After Second Vaccination

  Blood was collected from all participants at 8, 15, 22 and 29 days after receipt of the second vaccination for assessment of plaque reduction neutralization titers. The peak titer for each participant was defined as the highest titer among all available measurements post second vaccination. The geometric mean for each group was then assessed from individual participants' peak titers.

  Day 7 through Day 31 after 2nd vaccination

• Percentage of Participants Reporting Moderate or Severe Solicited Local Injection Site Reactions After Receiving Vaccine Via the Stratis™ Compared to Syringe and Needle Administration

  Participants maintained a memory aid to record daily the occurrence of local injection site reactions for 15 days after vaccination based on their interference with daily activities (pain and itchiness at injection site, underarm pain and swelling) or based on a quantitative measurement of the reaction (redness, swelling). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions were present but did not interfere with daily activities. For the quantitative scale, severe reactions greater than 30 millimeters (mm), moderate reactions were 15-30mm, and mild reactions were 1-15mm. Participants are counted by the maximum severity on any of the 15 days, and for this outcome measure, only those reporting moderate or severe events are counted. Formal comparisons by Fisher's Exact test were conducted for Arm D (Stratis, Day 1,29) compared to A

  15 days after each vaccination

Secondary Outcomes (2)

• Geometric Mean Peak ELISA Titer After Second Vaccination

  Day 7 through 31 after the 2nd vaccination

• Number of Subjects Experiencing Serious Adverse Events (SAEs) Associated With IMVAMUNE

  Day 1 after the first vaccination through 180 days after the 2nd vaccination.

Study Arms (4)

Arm C

EXPERIMENTAL

88 subjects receive IMVAMUNE® 1x10\^8 TCID50/0.5 mL subcutaneously (SC) via syringe and needle on Days 1 and 22.

Biological: MVA Smallpox Vaccine

Arm B

EXPERIMENTAL

88 subjects receive IMVAMUNE® 1x10\^8 TCID50/0.5 mL subcutaneously (SC) via syringe and needle on Days 1 and 15.

Biological: MVA Smallpox Vaccine

Arm A

EXPERIMENTAL

88 subjects receive IMVAMUNE® 1x10\^8 TCID50/0.5 mL subcutaneously (SC) via syringe and needle on Days 1 and 29.

Biological: MVA Smallpox Vaccine

Arm D

EXPERIMENTAL

88 subjects receive IMVAMUNE® 1x10\^8 TCID50/0.5 mL subcutaneously (SC) via Stratis™ on Days 1 and 29.

Biological: MVA Smallpox Vaccine

Interventions

MVA Smallpox Vaccine BIOLOGICAL

Subjects receive two dose regimen of IMVAMUNE® (1x10\^8 TCID50/0.5 mL per dose) via the SC route using either a syringe and needle or the Stratis™ system. Arm A receives doses via syringe and needle on days 1 and 29; Arm B receives doses via syringe and needle on days 1 and 15, Arm C receives doses via syringe and needle on days 1 and 22, Arm D receives doses via Stratis on days 1 and 29.

Arm A; Arm B; Arm C; Arm D

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 40 years of age, inclusive.
• Read, signed, and dated informed consent document.
• Available for follow-up for the planned duration of the study (six months after last immunization).
• Acceptable medical history by screening evaluation and limited physical assessment.
• If the subject is female and of childbearing potential, negative serum or urine pregnancy test at screening and within 24 hours prior to vaccination.
• If the subject is female and of childbearing potential\*, she agrees to practice abstinence\*\* or use acceptable contraception\*\*\* through 56 days after the last vaccination in order to avoid pregnancy:
• \* a woman is considered of childbearing potential unless post-menopausal (\>/= 1 year without menses) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy)
• \*\*No sexual intercourse with men (vaginal penetration by a penis, coitus)
• \*\*\*Acceptable contraception methods are restricted to effective devices (IUDs, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, condoms with spermicidal agents, monogamous relationship with a vasectomized partner who has been vasectomized for 6 months or more prior to study entry, or successful Essure placement with documented confirmation test at least 3 months after the procedure, and any other FDA-approved contraceptive method
• Negative test for HIV.
• Alanine Aminotransferase (ALT) \<1.25 times the central lab upper limit of normal.
• Negative hepatitis B surface antigen and negative antibody to hepatitis C virus.
• Negative urine glucose and negative or trace urine protein by dipstick or urinalysis.
• Adequate renal function (defined as a serum creatinine not exceeding the central lab's upper limit of normal).
• Electrocardiogram (ECG) with no clinically significant abnormalities\*

You may not qualify if:

• History of immunodeficiency.
• Typical vaccinia scar.
• Known or suspected history of smallpox vaccination including MVA alone or as a vector, as well as other investigational smallpox vaccines.
• Military service prior to 1991 or after January 2003.
• Known or suspected significant underlying illness including, but not limited to, clinically significant liver disease, diabetes mellitus, or moderate to severe kidney impairment.
• Malignancy (not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site) or history of skin cancer at the vaccination site.
• Active autoimmune disease. Persons with vitiligo or thyroid disease (e.g., taking thyroid hormone replacement) are not excluded.
• History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor\*
• \*Subjects with a not clinically relevant heart murmur, i.e., without any pathological ECG/arrhythmias or under treatment are not excluded.
• Systolic blood pressure \>/= 150mmHg or diastolic blood pressure \>/= 100mmHg.
• 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 (NCEP) risk assessment tool\*
• \*NOTE that this criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply:
• have smoked a cigarette in the past month, and/or
• have hypertension (defined as systolic blood pressure \>140 mm Hg) or are on antihypertensive medication, and/or
• have a family history of coronary heart disease in male first-degree relative (father or brother) \<55 years of age or a female first-degree relative (mother or sister) \<65 years of age

Sponsors & Collaborators

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

Study Sites (6)

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, 30030-1705, United States

Location

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

University of Maryland Medical System - General Clinical Research Center (GCRC)

Baltimore, Maryland, 21201-1544, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Group Health Research Institute - Seattle - Vaccines and Infectious Diseases

Seattle, Washington, 98101-1466, United States

Location

Related Publications (1)

• Jackson LA, Frey SE, El Sahly HM, Mulligan MJ, Winokur PL, Kotloff KL, Campbell JD, Atmar RL, Graham I, Anderson EJ, Anderson EL, Patel SM, Fields C, Keitel W, Rouphael N, Hill H, Goll JB. Safety and immunogenicity of a modified vaccinia Ankara vaccine using three immunization schedules and two modes of delivery: A randomized clinical non-inferiority trial. Vaccine. 2017 Mar 23;35(13):1675-1682. doi: 10.1016/j.vaccine.2017.02.032. Epub 2017 Feb 27.

  PMID: 28256358 DERIVED

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

Results Point of Contact

• Title: Lisa Jackson, M.D., M.P.H.
• Organization: Group Health Research Institute

Jackson.L@ghc.org

206-442-5216

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2013
• First Posted: April 9, 2013
• Study Start: June 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: September 7, 2016
• Results First Posted: December 11, 2015

Record last verified: 2015-05

Locations

US (6)