Clinical trial NCT04232280: Dose-Finding Trial to Evaluate the Safety and Immunogenicity of Cytomegalovirus (CMV) Vaccine mRNA-1647 in Healthy Adults
Official title: A Phase 2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Finding Trial to Evaluate the Safety and Immunogenicity of Cytomegalovirus Vaccine mRNA-1647 in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus Infection
Keywords: Moderna
mRNA-1647
Cytomegalovirus
CMV
Cytomegalovirus Vaccine
Cytomegalovirus Infections
Cytomegalovirus Congenital
Virus Diseases
Infection Viral
DNA Virus Infections
Messenger RNA
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-18
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: This clinical study will assess the safety and immunogenicity of 3 dose levels of mRNA-1647 cytomegalovirus vaccine in CMV-seronegative and CMV-seropositive healthy adults 18-40 years of age.

Detailed description: mRNA-1647-P202 is a 2-part study. Part 1 of the study evaluates the safety and immunogenicity of 3 dose levels of mRNA-1647 vaccine or placebo, administered on a 0, 2, 6-month schedule in healthy CMV-seronegative and CMV-seropositive males and females, 18 to 40 years of age. A planned interim analysis of safety and immunogenicity through Month 3 (1 month after the second dose) of Part 1 of the study informed the selection of the middle dose level for further development. Part 2 of the study is designed to further evaluate the safety and immunogenicity of the middle dose level of mRNA-1647 vaccine or placebo on a 0, 2, 6-month schedule in approximately 200 healthy participants 18 to 40 years of age, comprised of CMV-seronegative and CMV-seropositive female population, which includes the target population for the pivotal Phase 3 efficacy trial.

Eligibility criteria: Inclusion Criteria:

* Male or female 18-40 years of age (Part 1); Female 18-40 years of age (Part 2)
* Understands and agrees to comply with the trial procedures and provides written informed consent
* According to the assessment of the Investigator, is in good general health and is capable of complying with trial procedures
* Body mass index (BMI) 18-35 kilograms/meter (kg/m\^2)
* Female participants must either be of non-childbearing potential or use acceptable methods of contraception from at least 28 days prior to the first vaccination and through 3 months following last vaccination and is not breastfeeding.
* Male participants must agree to practice adequate contraception from the time of the first vaccination and through 3 months after the last vaccination.

Exclusion Criteria:

* Acutely ill or febrile on the day of the first vaccination
* Prior receipt of any CMV vaccine
* Abnormal screening safety laboratory test results
* Diagnosis or condition that, in the judgment of Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to trial procedures
* Has received or plans to receive a vaccine ≤28 days prior to the first vaccination or plans to receive a non-study vaccine within 28 days prior to or after any study vaccination, except for any licensed influenza vaccine which can be administered \>14 days before or after any study vaccination. COVID-19 vaccines (regardless of manufacturer) may be administered \>7 days but preferably \>14 days before or after any study vaccination, with the intention of prioritizing COVID-19 vaccination over all other considerations.
* Prior receipt of chronic systemic immunosuppressants or immune-modifying drugs
* Receipt of intravenous immunoglobulins or plasma products within 3 months prior to the day of the first study vaccination
* Previous receipt of medications in lipid nanoparticle (LNP) formulation (Part 1 participants only)
* Has donated ≥450 milliliters (mL) of blood products within 28 days of the Screening visit
* Participated in an interventional clinical trial within 28 days prior to the day of enrollment
* Is an immediate family member or household member of trial personnel

Primary outcomes:
measure: Frequency of Solicited Local and Systemic Adverse Reactions (ARs)
timeFrame: Up to Day 175 (7 days following last dose administration)
measure: Frequency of Unsolicited Adverse Events (AEs)
timeFrame: Up to Day 196 (28 days following last dose administration)
measure: Frequency of Medically-Attended Adverse Events (MAAEs)
timeFrame: Up to Day 336 (6 months following last dose administration)
measure: Frequency of Serious Adverse Events (SAEs)
timeFrame: Up to Day 504 (1 year following last dose administration)
measure: Change from Baseline in Geometric Mean Titer (GMT) of Serum Neutralizing Anti-CMV Antibodies Against Epithelial Cell Infection and Against Fibroblast Infection
timeFrame: Baseline, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
measure: Proportion of Participants with ≥2-Fold, 3-Fold, and 4-Fold Increases in Neutralizing Antibodies (nAb) over Baseline Against Epithelial Cell Infection and Against Fibroblast Infection
timeFrame: Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, and Day 504
Secondary outcomes:
measure: Change from Baseline in GMT of Anti-Glycoprotein B (gB) Specific Immunoglobulin G (IgG) and Anti-Pentamer Specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) of Post-Baseline/Baseline Titers
timeFrame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
measure: Change from Baseline in Associated GMR of Anti-gB Specific IgG and Anti-Pentamer Specific IgG as Measured by ELISA of Post-Baseline/Baseline Titers
timeFrame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
measure: Change from Baseline in GMT of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection at Each Timepoint, in the CMV-Seropositive Group and in the CMV-Seronegative Group
timeFrame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
measure: Change from Baseline in GMR of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection at Each Timepoint, in the CMV-Seropositive Group and in the CMV-Seronegative Group
timeFrame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
measure: Proportion of Participants with ≥2-Fold, 3-Fold, and 4-Fold Increases over Baseline of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection
timeFrame: Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, and Day 504
measure: Change from Baseline in GMT of Antigen-Specific IgG (ELISA) at each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups
timeFrame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
measure: Change from Baseline in GMR of Antigen-Specific IgG (ELISA) at each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups
timeFrame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Benchmark Research
state: California
city: Peoria
country: United States
facility: Optimal Research
state: Illinois
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Lexington
country: United States
facility: Alliance for Multispecialty Research
state: Kentucky
city: Columbus
country: United States
facility: Aventiv Research Inc
state: Ohio
city: Austin
country: United States
facility: Tekton Research Inc
state: Texas
city: Victoria
country: United States
facility: Crossroads Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Foothill Family Clinic
state: Utah
city: Salt Lake City
country: United States
facility: Foothill Family Clinic-South Clinic
state: Utah
Study officials:
References: