An Evaluation of a Cytomegalovirus (CMV) Vaccine (ASP0113) in CMV-Seropositive and CMV-Seronegative Healthy Subjects and CMV-Seronegative Dialysis Patients

NCT02103426 | Completed Phase 1

• 1 other identifier: 0113-CL-0004
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of the study is to determine whether ASP0113 (a CMV deoxyribonucleic acid \[DNA\] vaccine) can be detected in plasma after intramuscular (IM) injections, and to determine whether CMV-seropositive healthy volunteers, CMV-seronegative healthy volunteers, CMV-seronegative dialysis patients mount an immune response to the CMV proteins produced by the vaccine after repeated ASP0113 IM injection.

Conditions

Dialysis; Healthy Subjects; Cytomegalovirus Infection

Keywords

Cytomegalovirus; ASP0113; CMV-seropositive; Healthy subjects; CMV-seronegative; Dialysis

Outcome Measures

Primary Outcomes (11)

• ASP0113 plasmids pharmacokinetics in plasma: AUC (Part 1 and Part 2)

  Area under the curve (AUC)

  Day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21 and 28 for Part 1; Day 1, 2, 3, 4, 5, 6, 7 and weeks 5, 9 and 25 for Part 2)

• ASP0113 plasmids pharmacokinetics in plasma: Cmax (Part 1 and Part 2)

  Maximum Concentration (Cmax)

  Day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21 and 28 for Part 1; Day 1, 2, 3, 4, 5, 6, 7 and weeks 5, 9 and 25 for Part 2

• ASP0113 plasmids pharmacokinetics in plasma: Tmax (Part 1 and Part 2)

  Time to maximum concentration (Tmax)

  Day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21 and 28 for Part 1; Day 1, 2, 3, 4, 5, 6, 7 and weeks 5, 9 and 25 for Part 2

• ASP0113 plasmids pharmacokinetics in plasma: Apparent clearance (Part 1 and Part 2)

  Day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21 and 28 for Part 1; Day 1, 2, 3, 4, 5, 6, 7 and weeks 5, 9 and 25 for Part 2

• ASP0113 plasmids pharmacokinetics in plasma: apparent volume of distribution (Part 1 and Part 2)

  Day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21 and 28 for Part 1; Day 1, 2, 3, 4, 5, 6, 7 and weeks 5, 9 and 25 for Part 2

• ASP0113 plasmids pharmacokinetics in plasma: half-life (Part 1 and Part 2)

  Day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21 and 28 for Part 1; Day 1, 2, 3, 4, 5, 6, 7 and weeks 5, 9 and 25 for Part 2

• pp65 protein in white blood cells (WBCs) using pp65 antigenemia assay (Part 1 and Part 2)

  Day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21 , 28 for Part 1; Day 1, 10, 14, weeks 5, 7, 9, 11, 25 and 27 for Part 2

• Immunogenicity: Relative units/ml of anti-gB antibodies in serum as detected by enzyme-linked immunosorbent assay (ELISA) (Part 2)

  Day 1 and weeks 3, 5, 7, 9, 11, 25 and 27 (Part 2)

• Immunogenicity: Number of pp65-specific Interferon (IFN)-gamma producing T-cells in isolated peripheral blood mononuclear cells (PBMCs) upon pp65 peptide stimulation as assayed by flow cytometry with intracellular cytokine staining (ICS) (Part 2)

  Day 1 and weeks 3, 5, 7, 9, 11, 25 and 27 (Part 2)

• Immunogenicity: Amount of IFN-gamma produced by CMV peptide-stimulated T-cells in whole blood using the QuantiFERON T-cell CMV assay (Part 2)

  Day 1 and weeks 3, 5, 7, 9, 11, 25 and 27 (Part 2)

• Safety assessed by clinical labs, vital signs, and adverse events including local and systemic reactogenicity

  Up to Day 28 (Part 1), Up to 7 months (Part 2)

Study Arms (10)

Part 1: ASP0113 CMV-seropositive healthy cohort

EXPERIMENTAL

5 mg single dose IM injection

Drug: ASP0113

Part 1: ASP0113 CMV-seronegative healthy cohort

EXPERIMENTAL

5 mg single dose IM injection

Drug: ASP0113

Part 1: Placebo CMV-seropositive healthy cohort

PLACEBO COMPARATOR

single dose IM injection

Drug: Placebo

Part 1: Placebo CMV-seronegative healthy cohort

PLACEBO COMPARATOR

single dose IM injection

Drug: Placebo

Part 2: ASP0113 CMV-seropositive healthy cohort

EXPERIMENTAL

4 IM injections of ASP0113

Drug: ASP0113

Part 2: ASP0113 CMV-seronegative healthy cohort

EXPERIMENTAL

4 IM injections of ASP0113

Drug: ASP0113

Part 2: ASP0113 CMV-seronegative dialysis cohort

EXPERIMENTAL

4 IM injections of ASP0113

Drug: ASP0113

Part 2: Placebo CMV-seropositive healthy cohort

PLACEBO COMPARATOR

4 placebo IM injections

Drug: Placebo

Part 2: Placebo CMV-seronegative healthy cohort

PLACEBO COMPARATOR

4 placebo IM injections

Drug: Placebo

Part 2: Placebo CMV-seronegative dialysis cohort

PLACEBO COMPARATOR

4 placebo IM injections

Drug: Placebo

Interventions

ASP0113 DRUG

intramuscular injection

Part 1: ASP0113 CMV-seronegative healthy cohort; Part 1: ASP0113 CMV-seropositive healthy cohort; Part 2: ASP0113 CMV-seronegative dialysis cohort; Part 2: ASP0113 CMV-seronegative healthy cohort; Part 2: ASP0113 CMV-seropositive healthy cohort

Placebo DRUG

intramuscular injection

Part 1: Placebo CMV-seronegative healthy cohort; Part 1: Placebo CMV-seropositive healthy cohort; Part 2: Placebo CMV-seronegative dialysis cohort; Part 2: Placebo CMV-seronegative healthy cohort; Part 2: Placebo CMV-seropositive healthy cohort

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body Mass Index (BMI) range of 18.5 - 35.0 kg/m2; weighs at least 50 kg at Screening.
• Female subject must not be lactating and must not be breast feeding within 3 months before Screening or during the study period and for 28 days after final injection.
• Female subject must not donate ova starting at Screening and throughout the study period and for 28 days after final injection.
• Highly likely to comply with the protocol and complete the study.
• Estimated creatinine clearance calculated using the Cockcroft-Gault equation of \> 80 mL/min/1.73m2 (normal renal function).
• BMI range of 18.5 - 40.0 kg/m2; weighs at least 50 kg at Screening.
• Female subject must not be lactating and must not be breast feeding within 3 months before Screening or during the study period and for 30 days after final injection.
• Female subject must not donate ova starting at Screening and throughout the study period and for 28 days after final study drug administration.
• Must have adequate venous access.
• Highly likely to comply with the protocol and complete the study.
• Must currently be receiving hemodialysis treatment and for a period of at least 6 months prior to Screening.
• CMV-seronegative at Screening.

You may not qualify if:

• Female subject is pregnant at Screening.
• Any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies).
• Any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal (for healthy subjects only) and/or other major disease or malignancy (except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully or cancer in situ of the cervix uteri that has been handled by local surgery).
• History or evidence of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, scleroderma, psoriasis, psoriatic arthritis and inflammatory bowel disease.
• Febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (non-cutaneous) infection within 1 week prior to day -14.
• Any of the liver function tests (LFT) (aspartate amino-transferase \[AST\] or alanine aminotransferase \[ALT\] alkaline phosphatase (ALP), gamma-glutamyl transferase \[GGT\], total bilirubin \[TBil\]) outside of normal limits at Screening.
• Mean pulse \< 40 or \> 90 beats per minute (bpm), mean systolic blood pressure (SBP) \> 160 mmHg or mean diastolic blood pressure (DBP) \> 90 mmHg taken in triplicate after the subject has been resting in a sitting position for at least 5 minutes at Screening.
• Positive serology test for hepatitis B surface antigen (HBsAg) or hepatitis core immunoglobulin M (HBc \[IgM\]) antibody, anti-hepatitis A virus (HAV) IgM or anti-human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2) at Screening.
• Positive serology test for anti-hepatitis C virus (HCV) and a confirmatory positive reflex viral load test at Screening.
• Current/ active CMV infection as evidenced by positive CMV Polymerase chain reaction (PCR) plasma results at Screening.
• Any known or suspected hypersensitivity to ASP0113 or any components of the formulation used, including aminoglycosides as kanamycin is used during the manufacturing of the vaccine.
• Use of any prescribed or non-prescribed drugs, alternative and complementary medications, except for vitamins, contraceptives, hormone replacement therapy and occasional acetaminophen (to a maximum of 2 g/day), within 14 days prior to first injection with ASP0113.
• Vaccination with killed vaccines (including e.g., influenza and pneumococcal), or allergy treatment with antigen injections within 15 days prior to day -1.
• Vaccination with live attenuated vaccines within 30 days prior to day -1.
• Participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to day 1.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Vical: collaborator

Study Sites (4)

Site US10009

Los Angeles, California, 90017, United States

Location

Site US10003

Orlando, Florida, 32809, United States

Location

Site US10001

Baltimore, Maryland, 21225, United States

Location

Site US10004

Houston, Texas, 77099, United States

Location

Related Links

• Link to results on Astellas Clinical Study Results website

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2014
• First Posted: April 3, 2014
• Study Start: December 30, 2013
• Primary Completion: May 10, 2016
• Study Completion: May 10, 2016
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)