Study to Evaluate Safety, Tolerability, and Immunogenicity of Candidate Human Cytomegalovirus Vaccine in Healthy Adults

Cytomegalovirus Infections Clinical Trial

Official title:

A Phase 1 Randomized, Observer-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability, and Immunogenicity of the Candidate Human Cytomegalovirus Vaccine (VBI-1501) in Healthy Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02826798
• Other study ID #: VBI-1501
• Status: Completed
• Phase: Phase 1
• Start date: June 23, 2016
• Est. completion date: August 24, 2017

Study information

• Verified date: April 2020
• Source: VBI Vaccines Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the safety and effectiveness of four different doses of cytomegalovirus vaccines in healthy adults.

Description:

This study is designed to assess safety and immunogenicity of four dose formulations of cytomegalovirus (CMV) vaccine (0.5 μg gB content with aluminum phosphate (alum), 1.0 μg glycoprotein B (gB) content with alum, 2.0 μg gB content with alum, or 1.0 μg gB content (without alum) as compared with placebo in approximately 125 healthy CMV-seronegative volunteer participants between 18 and 40 years of age.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: August 24, 2017
• Est. primary completion date: September 15, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Generally healthy adult female and male 18 to 40 years of age, inclusive;

2. Serologically confirmed to be CMV seronegative at screening;

3. Female volunteers must agree to use an adequate contraception method as deemed appropriate by the investigator

4. Sign an informed consent document indicating understanding of the purpose and procedures required for the study and willingness to participate in the study

Exclusion Criteria:

1. History of or current clinically significant medical illness or any other illness that in the opinion of the investigator interferes with the interpretation of the study results

2. Clinically significant abnormal physical examination, vital signs, or clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening as determined by the investigator

3. Previous receipt of any cytomegalovirus vaccine

4. History of allergic reactions or anaphylactic reaction to any vaccine component

5. Pregnant or breastfeeding or plans to conceive from two weeks before the study start through six months after the last dose of study vaccine

6. Known or suspected impairment of immunological function, including but not limited to autoimmune diseases, splenectomy, or HIV/AIDS

7. Chronic administration (defined as more than 14 days in total) of immune-suppressive or other immune-modifying drug with six months prior to the product dose (for corticosteroids, this is defined as prednisone =20 mg/day or equivalent). Inhaled and topical steroids are allowed

8. Participation in another clinical study within 30 days or plans to participate in another treatment based clinical study during the conduct of the present study

9. Any skin abnormality or tattoo that would limit post-vaccination injection site assessment

10. Any history of cancer requiring chemotherapy or radiation within 5 years of randomization or current disease

11. Are family members of study center staff

Related Conditions & MeSH terms

• Cytomegalovirus Infections
• Infection

Intervention

Drug:
• VBI-1501A 0.5 µg
VBI-1501A: 0.5 µg with alum-administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168
• VBI-1501A 1.0 µg
VBI-1501A: 1.0 µg with alum with alum-administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168
• VBI-1501A 2.0 µg
VBI-1501A: 2.0 µg with alum-administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168
• VBI-1501 1.0 µg
VBI-1501: 1.0 µg without alum-administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168
• Placebo
buffer/sucrose used for VBI-1501 suspension- administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168.

Locations

Country	Name	City	State
Canada	Canadian Center for Vaccinology; IWK Health Centre	Halifax	Nova Scotia
Canada	McGill University Health Centre - Vaccine Study	Pierrefonds	Quebec
Canada	Vaccine Evaluation Center	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
VBI Vaccines Inc.	Clinical Trial Data Services, LLC

Country where clinical trial is conducted

Canada, 

References & Publications (19)

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Adler SP. Human CMV vaccine trials: what if CMV caused a rash? J Clin Virol. 2008 Mar;41(3):231-6. Epub 2007 Dec 21. Review. — View Citation

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FDA Guidance for industry (Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical studies, September 2007. Available at: http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm091977.pdf.

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Griffiths PD, Stanton A, McCarrell E, Smith C, Osman M, Harber M, Davenport A, Jones G, Wheeler DC, O'Beirne J, Thorburn D, Patch D, Atkinson CE, Pichon S, Sweny P, Lanzman M, Woodford E, Rothwell E, Old N, Kinyanjui R, Haque T, Atabani S, Luck S, Prideaux S, Milne RS, Emery VC, Burroughs AK. Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial. Lancet. 2011 Apr 9;377(9773):1256-63. doi: 10.1016/S0140-6736(11)60136-0. — View Citation

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Loomis RJ, Lilja AE, Monroe J, Balabanis KA, Brito LA, Palladino G, Franti M, Mandl CW, Barnett SW, Mason PW. Vectored co-delivery of human cytomegalovirus gH and gL proteins elicits potent complement-independent neutralizing antibodies. Vaccine. 2013 Jan 30;31(6):919-26. doi: 10.1016/j.vaccine.2012.12.009. Epub 2012 Dec 14. — View Citation

Macagno A, Bernasconi NL, Vanzetta F, Dander E, Sarasini A, Revello MG, Gerna G, Sallusto F, Lanzavecchia A. Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex. J Virol. 2010 Jan;84(2):1005-13. doi: 10.1128/JVI.01809-09. Epub 2009 Nov 4. — View Citation

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Plotkin SA. Is there a formula for an effective CMV vaccine? J Clin Virol. 2002 Aug;25 Suppl 2:S13-21. Review. — View Citation

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Local and Systemic Adverse Events During Seven-Day Follow-Up Period		Day of vaccine administration (days 0, 56, 168) and six subsequent days
Primary	Number of Participants With Any Adverse Event		Following each of the 3 injections of study vaccine, the occurrence of adverse events was captured during a 28-day follow-up period as well as through Day 336 or early withdrawal.
Primary	Number of Participants With Any Serious Adverse Event		Through Day 336 or early withdrawal
Primary	Number of Participants With Any Hematological or Biochemical Laboratory Abnormality	Blood and urine samples were collected at screening for all evaluations with additional blood samples obtained on Days 28, 56, 84, 168, 196, 280, and 336. The following clinical laboratory evaluations were performed: Biochemistry: alanine aminotransferase; aspartate aminotransferase; creatinine; blood urea nitrogen; Hematology: neutrophils, lymphocytes, eosinophils, hemoglobin, platelet count, white blood cell count; Infection status: HIV, hepatitis B, hepatitis C, and cytomegalovirus; and Urinalysis: blood, glucose, protein.	Through Day 336 or early withdrawal
Secondary	Geometric Mean Titer of Antibody Binding to CMV gB		Through Day 336 or early withdrawal
Secondary	Geometric Mean Titer of Antibody Avidity Index Value Against gB	To measure the avidity of responses against CMV gB protein, a standard ELISA assay using recombinant gB protein which did or did not include treatment with 5M urea for 30 minutes of samples after sera had been incubated with recombinant protein. The reported value, or Avidity Index, represents the percent of signal measured in ELISA after treatment with urea relative to samples not exposed to urea.	Through Day 336 or early withdrawal
Secondary	Geometric Mean Titer of Neutralizing Antibody Against CMV Infection of Fibroblast Cells		Through Day 196 or early withdrawal
Secondary	Geometric Mean Titer of Neutralizing Antibody Against CMV Infection of Epithelial Cells		Through Day 336 or early withdrawal