Ebola CVD-Mali #2000 (Bivalent) VRC-EBOAdc069-00-vp (cAd3-EBO)

NCT02368119 | Completed Phase 1 DMC

• 1 other identifier: HP-00062548
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Ebola virus causes an infection known as Ebola virus disease (EVD). This it is generally a severe disease which can also lead to death. The 2014 outbreak of EVD in West Africa is the largest ever. Researchers want to develop a vaccine to prevent Ebola infection. This study will assess the safety of a single dose of the bivalent Ebola Zaire candidate vaccine VRC-EBOADC069-00-VP (cAD3-EBO) when administered to healthy Malian adult volunteers, age 18-65 years (mostly health care workers and other front line workers \[e.g., individuals who incinerate contaminated materials\]), at one of 2 dosage levels, 2.0 x 10(10) vp or 2 x 10(11) vp. It is impossible for someone to get an Ebola infection from this vaccine. Heterologous booster dose allocation - Each participant will be offered the opportunity to be included in the booster step of this study. After obtaining consent and the additional review of pertinent medical history, participants in each group will be randomized to receive the candidate booster vaccine, MVA-EbolaZ or placebo. This will be the first clinical trial in Mali with bivalent cAd3-based Ebola vaccine and the first where the dosage level contains \> 10(11) vp. It follows completion of a Phase Ib trial in Malian health care workers that tested three dosage levels of monovalent cAd3-EBO Z vaccine. The data generated in West Africans (Mali) on the tolerability and immunogenicity of the bivalent vaccine will be compared to clinical and immunologic responses documented in in parallel studies in East African subjects (Uganda) and North American subjects (NIH, Bethesda, MD, USA). Objectives:

• To see if an Ebola vaccine is safe and to study immune responses to it.
• To study the effect of the MVA-EbolaZ booster on the immune response Eligibility: \- Healthy adults ages 18-65.

Conditions

Ebola Virus Disease; Hemorrhagic Fever

Outcome Measures

Primary Outcomes (2)

• Solicited local reactogenicity - Number of participants with the specific outcome

  Occurrence of solicited local signs and symptoms following vaccination

  For 7 days following each vaccination

• Solicited systemic reactogenicity - Number of participants with the specific outcome

  Occurrence of solicited systemic signs and symptoms following vaccination

  For 7 days following each vaccination

Secondary Outcomes (1)

• Ebolavirus specific immunogenicity

  At 7, 14, 28, 56, 112 and 168 days after vaccination. For those who participate in booster substudy, additional samples will be collected at these time points and no further samples would be timed from the priming dose

Study Arms (2)

Group 1

EXPERIMENTAL

VRC-EBOADC069-00 VP (cAd3-EBO bivalent (Zaire plus Sudan) vaccine (2 x 10(10) vp (n=10) or VRC-EBOADC069-00 VP (cAd3-EBO bivalent (Zaire plus Sudan) vaccine (2 x 10(11) vp (n=10). Randomization to booster of MVA-EbolaZ or PBS placebo will be completed 4 to 16 weeks after priming dose.

Biological: VRC-EBOADC069-00-vp; Biological: MVA-EbolaZ; Other: Placebo

Group 2

EXPERIMENTAL

VRC-EBOADC069-00 VP (cAd3-EBO bivalent (Zaire plus Sudan) vaccine (2 x 10(10) vp (n=20) or VRC-EBOADC069-00 VP (cAd3-EBO bivalent (Zaire plus Sudan) vaccine (2 x 10(11) vp (n=20). Randomization to booster of MVA-EbolaZ or PBS placebo will be completed 4 to 16 weeks after priming dose.

Biological: VRC-EBOADC069-00-vp; Biological: MVA-EbolaZ; Other: Placebo

Interventions

VRC-EBOADC069-00-vp BIOLOGICAL

IM Injection of cAd3-EBO bivalent (Zaire plus Sudan) vaccine (2 x 10(10) vp)

Also known as: cAd3-EBO at 2x10(10) vp

Group 1; Group 2

MVA-EbolaZ BIOLOGICAL

IM injection of MVA-EbolaZ vaccine

Group 1; Group 2

Placebo OTHER

IM injection injection of Phosphate Buffered Saline

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults aged 18 to 65 years
• Able and willing (in the Investigator's opinion) to comply with all study requirements
• For females only, willingness to practice continuous effective contraception (see section 6.4.3) during the study and a negative urine pregnancy test on the day(s) of screening and vaccination
• Agreement to refrain from blood donation during the course of the study
• Provide written informed consent
• Laboratory criteria within 30 days prior to enrollment:
• Hemoglobin ≥ 11.0 g/dL for women; ≥12.5 g/dL for men.
• White blood cells (WBC) = 2,500-11,000 cells/mm3.
• Neutrophil count = 1200 - 7000 cells/mm3
• Lymphocyte count ≥ 800 cells/mm3
• Eosinophil count = 0 - 500 cells/mm3
• Platelets = 125,000 - 400,000/mm3
• Alanine aminotransferase (ALT) = 10-45 IU/L
• Serum creatinine = 54-145 umol/L.
• HIV-uninfected as evidenced by a negative HIV diagnostic test.

You may not qualify if:

• Recent exposure to Ebola virus infection (this is not a post-exposure vaccine)
• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
• Prior receipt of an investigational Ebola or Marburg vaccine, a chimpanzee adenovirus vectored vaccine, MVA vectored vaccine (for booster study) or any other investigational vaccine likely to impact on interpretation of the trial data
• Receipt of any live, attenuated vaccine within 28 days prior to enrolment
• Receipt of any subunit or killed vaccine within 14 days prior to enrolment
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including urticaria, respiratory difficulty or abdominal pain
• Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
• Any history of anaphylaxis in reaction to vaccination
• Pregnancy, lactation or willingness/intention to become pregnant during the study
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of serious psychiatric condition
• Poorly controlled asthma or thyroid disease
• Seizure in the past 3 years or treatment for seizure disorder in the past 3 years

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Centre pour le Developpement des Vaccins - Mali

Bamako, Mali

Location

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola; Hemorrhagic Fevers, Viral

Condition Hierarchy (Ancestors)

RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Study Officials

• Myrons M Levine, MD DTPH

  University of Maryland, Baltimore

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Pediatrics & Infectious Tropical Diseases

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 20, 2015
• Study Start: March 1, 2015
• Primary Completion: September 27, 2016
• Study Completion: September 27, 2016
• Last Updated: September 26, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)