Dose Ranging Trial to Assess Safety and Immunogenicity of V590 (COVID-19 Vaccine) in Healthy Adults (V590-001)

NCT04569786 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: V590-001
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 7

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of V590 versus placebo and to assess the immunogenicity of V590 on Day 28. The primary hypothesis is that at least one well-tolerated dose of V590 increases the geometric mean titers (GMTs) of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike serum neutralizing antibody, as measured by plaque reduction neutralization test (PRNT), compared to placebo.

Conditions

Coronavirus Disease (COVID-19)

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants With at Least 1 Solicited Injection Site Adverse Event

  An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Solicited injection site AEs (injection site redness/erythema, pain, swelling) were assessed.

  Up to 5 days post-vaccination

• Percentage of Participants With at Least 1 Solicited Systemic Adverse Event

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Solicited systemic AEs (joint stiffness/arthralgia, tiredness/fatigue, headache, joint swelling, muscle pain/myalgia, nausea, oral disorder, and rash) were assessed.

  Up to 28 days post-vaccination

• Percentage of Participants With at Least 1 Unsolicited Adverse Event

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Participants with reported unsolicited AEs were assessed.

  Up to ~28 days post-vaccination

• Percentage of Participants With at Least 1 Medically Attended Adverse Event

  A medically attended adverse event (MAAE) is an AE in which medical attention is received during an unscheduled, non-routine outpatient visit, such as an emergency room visit, office visit, or an urgent care visit with any medical personnel for any reason. Any MAAE was assessed.

  Up to 28 days post-vaccination

• Percentage of Participants With at Least 1 Serious Adverse Event

  A serious adverse event (SAE) is "life threatening," requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other important medical event. Any SAE was assessed. Active monitoring of SAEs occurred through Day 28 but were collected per protocol till study completion/termination or \~90 days post-vaccination.

  Active monitoring through Day 28 post-vaccination (Up to a maximum of ~90 days post-vaccination)

• Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by Plaque Reduction Neutralization Test

  Serum samples were collected and the presence of serum neutralization antibodies (SNAs) were assessed using plaque reduction neutralization test (PRNT). Geometric mean titers (GMTs) and 95% confidence intervals (CIs), GMT ratios and 90% CIs, and p-values are estimated from a longitudinal data analysis (LDA) model and are provided in accordance with the statistical analysis plan.

  28 days post-vaccination

Secondary Outcomes (7)

• Geometric Mean Titers for SNAs as Measured by PRNT- 7 Days

  7 days post-vaccination

• Geometric Mean Titers for SNAs as Measured by PRNT- 14 Days

  14 days post vaccination

• Geometric Mean Titers for Total Anti-Spike Immunoglobulin G Antibodies as Measured by Enzyme-Linked Immunosorbent Assay

  7, 14, and 28 days post vaccination

• Number of Participants With Vaccine Viremia as Measured by Reverse Transcription-Polymerase Chain Reaction

  1, 2, 3, 4, 5, 6, 7, 14 and 28 days post-vaccination

• Number of Participants With Viral Shedding in Saliva as Measured by RT-PCR

  1, 2, 3, 4, 5, 6, 7, 14, and 28 days post-vaccination

Study Arms (9)

V590 5.00x10^5 pfu (Panel A)

EXPERIMENTAL

Participants in this 18 to 54-year-old SARS-CoV-2 seronegative cohort (Panel A) will receive a single dose of V590 5.00x10\^5 pfu or placebo on Day 1.

Biological: V590; Other: Placebo

V590 2.40x10^6 pfu (Panel B)

EXPERIMENTAL

Participants in this 18 to 54-year-old SARS-CoV-2 seronegative cohort (Panel B) will receive a single dose of 2.40x10\^6 pfu or placebo on Day 1.

Biological: V590; Other: Placebo

V590 1.15x10^7 pfu (Panel C)

EXPERIMENTAL

Participants in this 18 to 54-year-old SARS-CoV-2 seronegative cohort (Panel C) will receive a single dose of 1.15x10\^7 pfu or placebo on Day 1.

Biological: V590; Other: Placebo

V590 5.55x10^7 pfu (Panel D)

EXPERIMENTAL

Participants in this 18 to 54-year-old SARS-CoV-2 seronegative cohort (Panel D) will receive a single dose of V590 5.55x10\^7 pfu or placebo on Day 1.

Biological: V590; Other: Placebo

Part 2: 5.00x10^5 pfu (Panel E)

EXPERIMENTAL

Participants in this ≥ 55 years old SARS CoV-2 seronegative cohort (Panel E) will receive a single dose of V590 5.00x10\^5 pfu or placebo on Day 1.

Biological: V590; Other: Placebo

Part 2: 2.40x10^6 pfu (Panel F)

EXPERIMENTAL

Participants in this ≥ 55 years old SARS-CoV-2 seronegative cohort (Panel F) will receive a single dose of 2.40x10\^6 pfu or placebo on Day 1.

Biological: V590; Other: Placebo

Part 2: 1.15x10^7 pfu (Panel G)

EXPERIMENTAL

Participants in this ≥ 55 years old SARS-CoV-2 seronegative cohort (Panel G) will receive a single dose of V590 1.15x10\^7 pfu or placebo on Day 1

Biological: V590; Other: Placebo

Part 2: 5.55x10^7 pfu (Panel H)

EXPERIMENTAL

Participants in this ≥ 55 years old SARS-CoV-2 seronegative cohort (Panel H) will receive a single dose of V590 5.55x10\^7 pfu or placebo on Day 1.

Biological: V590; Other: Placebo

Part 3: 5.55x10^7 pfu (Panel I)

EXPERIMENTAL

Participants in this 18 to 54-year-old SARS-CoV-2 seropositive cohort (Panel I) will receive a single dose of V590 5.55x10\^7 pfu or placebo on Day 1.

Biological: V590; Other: Placebo

Interventions

V590 BIOLOGICAL

Single dose of V590 administered via intramuscular (IM) injection with dosage levels of 5.00x10\^5 pfu/mL (Panels A, E), 2.40x10\^6 pfu/mL (Panels B,F), 1.15x10\^7 pfu/mL (Panels C, G), 5.55x10\^7 pfu/mL (Panels D, H, I).

Part 2: 1.15x10^7 pfu (Panel G); Part 2: 2.40x10^6 pfu (Panel F); Part 2: 5.00x10^5 pfu (Panel E); Part 2: 5.55x10^7 pfu (Panel H); Part 3: 5.55x10^7 pfu (Panel I); V590 1.15x10^7 pfu (Panel C); V590 2.40x10^6 pfu (Panel B); V590 5.00x10^5 pfu (Panel A); V590 5.55x10^7 pfu (Panel D)

Placebo OTHER

Placebo administered via IM injection.

Part 2: 1.15x10^7 pfu (Panel G); Part 2: 2.40x10^6 pfu (Panel F); Part 2: 5.00x10^5 pfu (Panel E); Part 2: 5.55x10^7 pfu (Panel H); Part 3: 5.55x10^7 pfu (Panel I); V590 1.15x10^7 pfu (Panel C); V590 2.40x10^6 pfu (Panel B); V590 5.00x10^5 pfu (Panel A); V590 5.55x10^7 pfu (Panel D)

Eligibility Criteria

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

You may qualify if:

• Is in overall good health based on medical history, physical examination, and vital sign (VS) measurements performed prior to randomization, as assessed by the investigator.
• Is in overall good health based on laboratory safety tests obtained at the screening visit.
• Has a body mass index (BMI) ≤30 kg/m2 inclusive (after rounding to the nearest whole number).
• Parts 1 and 2 (Panels A-H) only: Has negative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on both antibody and reverse transcription polymerase chain reaction (RT-PCR), at screening and upon start of domiciling.
• Part 3 (Panel I) only: Has positive serology (antibody) testing for SARS-CoV-2, also with negative SARS CoV-2 RT-PCR testing at screening and upon start of domiciling, and without symptoms of respiratory infection for at minimum 3 weeks preceding screening.
• Has been practicing social distancing for at least two weeks prior to planned start of domiciling and has had no close contacts with known active SARS-CoV-2 infection in that time period.
• Is male or female, from 18 years to 54 years of age inclusive (Parts 1 and 3 \[Panels A-D, I\]) or ≥ 55 years of age (Part 2 \[Panels E-H\]) at the time of signing the informed consent.
• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 2 months after administration of study intervention: be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent OR agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP), or is a WOCBP and using an acceptable contraceptive method, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle. A WOCBP must have a negative highly sensitive pregnancy test before the first dose of study intervention. If a urine test cannot be confirmed as negative, a serum pregnancy test is required.

You may not qualify if:

• Has a known hypersensitivity to any component of V590 or placebo.
• Has any known or suspected active clinically significant autoimmune disease or immunosuppressive condition, acquired or congenital, as determined by medical history and/or physical examination.
• Has thrombocytopenia or other coagulation disorder contraindicating intramuscular vaccination or repeated venipuncture.
• Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study or interfere with the participant's participation for the full duration of the study.
• Has a history of ongoing liver disease or, at the time of screening, has any one of the following: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 × Upper Limit of Normal (ULN), alkaline phosphatase and direct bilirubin \> ULN (total bilirubin may be up to 2 × ULN as long as direct bilirubin is equal to or below the ULN), or prothrombin time (PT) international normalized ratio (INR) \> 1.25.
• Has a history of asthma or allergic asthma that required systemic corticosteroids in the previous year.
• Has a history of Guillain-Barré syndrome.
• Has a history of diabetes mellitus, requiring medication at the time of assessment, OR has a hemoglobin A1c ≥ 6.5.
• Has a history of any medical condition that would put the participant at risk for severe SARS-CoV-2 disease as judged by the investigator.
• Has any ongoing, symptomatic, acute or chronic illness requiring medical or surgical care or any condition that is immunosuppressive.
• Is mentally or legally incapacitated, has significant emotional problems at the time of screening visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years.
• Has a history of cancer (malignancy).
• Participant has an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m\^2.
• Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to a vaccine or prescription or non-prescription drugs or food as judged by the investigator.
• Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)-1 or 2 antibodies. Individuals with antibodies to hepatitis C may be enrolled if hepatitis C viral load is negative and there is no evidence of or history of liver disease.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (7)

Celerion ( Site 0002)

Tempe, Arizona, 85283, United States

Location

Clinical Pharmacology of Miami ( Site 0003)

Miami, Florida, 33014, United States

Location

QPS Miami Research Associates ( Site 0005)

South Miami, Florida, 33143, United States

Location

Bio-Kinetic Clinical Applications (QPS) ( Site 0006)

Springfield, Missouri, 65802, United States

Location

Celerion ( Site 0001)

Lincoln, Nebraska, 68502, United States

Location

Alliance for Multispecialty Reseach, LLC ( Site 0004)

Knoxville, Tennessee, 37920, United States

Location

Worldwide Clinical Trials ( Site 0007)

San Antonio, Texas, 78217, United States

Location

Related Publications (2)

• Robbins JA, Tait D, Huang Q, Dubey S, Crumley T, Cote J, Luk J, Sachs JR, Rutkowski K, Park H, Schwab R, Howitt WJ, Rondon JC, Hernandez-Illas M, O'Reilly T, Smith W, Simon J, Hardalo C, Zhao X, Wnek R, Cope A, Lai E, Annunziato P, Guris D, Stoch SA. Safety and immunogenicity of intramuscular, single-dose V590 (rVSV-SARS-CoV-2 Vaccine) in healthy adults: Results from a phase 1 randomised, double-blind, placebo-controlled, dose-ranging trial. EBioMedicine. 2022 Aug;82:104138. doi: 10.1016/j.ebiom.2022.104138. Epub 2022 Jul 6.

  PMID: 35809371 DERIVED

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study was terminated based on an interim assessment of immunogenicity.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: September 30, 2020
• Study Start: October 29, 2020
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2021
• Last Updated: December 29, 2021
• Results First Posted: December 29, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share

Locations

US (7)