Randomized, Open-label Phase II Trial to Assess the Safety and Immunogenicity of MVA-BN Smallpox Vaccine in Immunocompromised Subjects With HIV Infection

NCT02038881 | Completed Phase 2 Results DMC

• 1 other identifier: POX-MVA-037
• Study Type: interventional
• Target: 87
• Locations: 2 countries
• Sites: 12

Brief Summary

The main purpose of this clinical trial is to generate additional safety data in a highly immunocompromised population. HIV-infected persons are considered excellent candidates to represent the highly immunocompromised population for enrolment in this trial. Additionally, the immune system's response (protection against smallpox as measured by the amount of antibodies produced) following injections of MVA-BN® smallpox vaccine will be evaluated. All participants in this trial will be randomly and evenly assigned to one of three groups to receive two, three or four injections. Group 1 will receive the standard regime consisting of one dose at each vaccination time point, Group 2 will receive two doses at each vaccination time point and Group 3 will receive a booster vaccination 12 weeks after the standard vaccination schedule with MVA-BN® smallpox vaccine. Participation in the trial is scheduled to last up to 75 weeks.

Conditions

Smallpox

Outcome Measures

Primary Outcomes (1)

• Number of Participants With SAEs

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

  within 75 weeks

Secondary Outcomes (23)

• Number of Participants With AESIs

  within 75 weeks

• Number of Participants With Related Grade >=3 Adverse Events

  within 29 days after any vaccination

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

  within 29 days after any vaccination

• Number of Unsolicited Non-serious Adverse Events: Intensity

  within 29 days after any vaccination

• Number of Participants With Solicited Local Adverse Events

  within 8 days after any vaccination

Study Arms (3)

Group 1 (standard regimen)

EXPERIMENTAL

One injection at Day 0 and Day 28 with IMVAMUNE® (MVA-BN®)

Biological: IMVAMUNE®

Group 2 (double dose regimen)

EXPERIMENTAL

Two injections at Day 0 and two injections at Day 28 with IMVAMUNE® (MVA-BN®)

Biological: IMVAMUNE®

Group 3 (booster regimen)

EXPERIMENTAL

One injection at Day 0 and Day 28 and one booster injection at week 12 with IMVAMUNE® (MVA-BN®)

Biological: IMVAMUNE®

Interventions

IMVAMUNE® BIOLOGICAL

0.5 ml Modified Vaccinia Ankara Strain - Bavarian Nordic (MVA-BN®) smallpox vaccine containing at least 1 x 10E8 TCID50 per ml

Also known as: IMVANEX®, MVA-BN® smallpox vaccine

Group 1 (standard regimen); Group 2 (double dose regimen); Group 3 (booster regimen)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects aged between 18-45 years, vaccinia-naïve.
• HIV-1 infection documented by ELISA and confirmed by Western blot at any time prior to study entry. HIV-1 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), HIV-1 culture, HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA), or a second antibody test other than ELISA is acceptable as an alternative test at any time prior to study entry.
• On stable antiretroviral therapy (ART) i.e. Combination ART for at least 6 months. Subject must be on the same ART regimen for at least 12 weeks with no change prior to enrollment in this clinical trial.
• Screening HIV-1 RNA \< 200 copies/ml by US Food and Drug Administration (FDA) approved PCR assay within 45 days prior to study entry.
• Current CD4 counts ≥ 100 cells/µl ≤ 500 cells/µl.
• Documented nadir CD4 count \< 200 cells/µl at any time prior to enrollment.
• Hemoglobin ≥ 9.0 g/dl for female subjects, ≥ 10.0 g/dl or male subjects.
• Platelets ≥ 100,000/mm3.
• Ability and willingness of subject to provide written informed consent.
• Body Mass Index (BMI) ≥ 18.5 and \< 35 kg/m2.
• Women of childbearing potential (WOCBP) 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 trial, and must avoid becoming pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal (defined as ≥ 12 months without a menstrual period) or surgically sterilized. Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products).
• WOCBP must have a negative serum pregnancy test at screening (SCR) and a negative urine pregnancy test within 24 hours prior to each vaccination.
• Absolute neutrophil count cells ≥ 750/mm3.
• Adequate renal function defined as a calculated Creatinine Clearance (CrCl) \> 60 ml/min as estimated by the Cockcroft-Gault equation.
• For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl x 72) = CrCl (ml/min)

You may not qualify if:

• Pregnant or breast-feeding women.
• Typical vaccinia scar.
• Known or suspected history of smallpox vaccination.
• History of vaccination with any poxvirus-based vaccine.
• Uncontrolled serious infection, i.e. not responding to antimicrobial therapy.
• History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject or would limit the subject's ability to complete the trial including uncontrolled diabetes as according to the 'Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events' Version 1.0, December 2004, Clarification August 2009.
• History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.
• 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 must not be vaccinated at the previous tumor site.
• History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders (except HIV infection, chronic or active Hepatitis-B-Virus or Hepatitis-C-Virus infection).
• Clinically significant psychiatric disorder not adequately controlled by medical treatment.
• History of coronary heart disease, myocardial infarction, angina pectoris, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor.
• Known 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 subjects 20 years of age and older.
• Current alcohol abuse (40 g/day for at least 6 month) and/or intravenous and/or intranasal drug abuse (within the past 6 months).
• Known allergy to MVA-BN® vaccine or any of its constituents, e.g. tris (hydroxymethyl)-amino methane, including known allergy to egg or aminoglycosides.

Sponsors & Collaborators

• Bavarian Nordic: lead

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Health for Life Clinic Little Rock

Little Rock, Arkansas, 72207, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Dupont Circle Physicians Group

Washington D.C., District of Columbia, 20009, United States

Location

Infectious Disease Associats of NW Florida Center for Prevention and Treatment of Infections Infectious Diseases Associates of NW FL

Pensacola, Florida, 32504, United States

Location

Rowan Tree Medical

Wilton Manors, Florida, 33305, United States

Location

University of Illinois - Chicago

Chicago, Illinois, 60612, United States

Location

University of Iowa Departments of Internal Medicine and Microbiology University of Iowa

Iowa City, Iowa, 52242, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Pennsylvania Clinical Trials Unit

Philadelphia, Pennsylvania, 19104, United States

Location

Clinical Research Puerto Rico, Inc.

San Juan, PR, 009091711, Puerto Rico

Location

Fundacion de Investigacion

San Juan, PR, 00927, Puerto Rico

Location

Related Publications (1)

• Overton ET, Lawrence SJ, Stapleton JT, Weidenthaler H, Schmidt D, Koenen B, Silbernagl G, Nopora K, Chaplin P. A randomized phase II trial to compare safety and immunogenicity of the MVA-BN smallpox vaccine at various doses in adults with a history of AIDS. Vaccine. 2020 Mar 4;38(11):2600-2607. doi: 10.1016/j.vaccine.2020.01.058. Epub 2020 Feb 11.

  PMID: 32057574 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: Program Lead, Clinical Operations
• Organization: Bavarian Nordic A/S

info@bavarian-nordic.com

+45 3326

Study Officials

• Edgar T Overton, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 17, 2014
• Study Start: April 28, 2014
• Primary Completion: May 10, 2017
• Study Completion: May 10, 2017
• Last Updated: April 2, 2020
• Results First Posted: April 2, 2020

Record last verified: 2020-03

Locations

PR (2); US (10)