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

NCT ID: NCT04569786

Last Updated: 2021-12-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

232 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-29

Study Completion Date

2021-02-18

Brief Summary

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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.

Detailed Description

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This study was terminated and study objectives, endpoints, and procedures were modified accordingly via Protocol Amendment 03. Analysis included the intervention doses (V590 5.00 x 10\^5 plaque forming units \[pfu\], V590 2.4 x 10\^6 pfu, V590 1.15 x 10\^7 pfu, V590 5.55 x 10\^7 pfu or placebo) as specified in the protocol.

Conditions

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Coronavirus Disease (COVID-19)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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V590 5.00x10^5 pfu (Panel A)

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.

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

V590 2.40x10^6 pfu (Panel B)

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.

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

V590 1.15x10^7 pfu (Panel C)

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.

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

V590 5.55x10^7 pfu (Panel D)

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.

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

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

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.

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

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

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.

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

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

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

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

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

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.

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

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

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.

Group Type EXPERIMENTAL

V590

Intervention Type 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).

Placebo

Intervention Type OTHER

Placebo administered via IM injection.

Interventions

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V590

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).

Intervention Type BIOLOGICAL

Placebo

Placebo administered via IM injection.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-study (screening) visit.
* A WOCBP who has a positive urine or serum pregnancy test before vaccination.
* A WOCBP who is breastfeeding.
* Has any unstable chronic medical condition, including one that has resulted in change in therapy (medication or other) in the 30 days prior to randomization or hospitalization in the previous year or might be predicted to result in hospitalization in the year after enrollment.
* Has received or is expected to receive any SARS-CoV-2 vaccine or other coronavirus vaccine during the study (except V590), is using investigational agents for prophylaxis of SARS-CoV-2 or is taking any systemic antiviral medications.
* Has received any intra-articular steroid injections within the 3 months prior to study vaccination or is expected to require intra-articular steroid injection during the study.
* Is receiving immunosuppressive therapy or has received immunosuppressive therapy within 6 months of enrollment.
* Has received a blood transfusion or blood products, including immunoglobulin, in the 3 months before anticipated study vaccination.
* Is expected to be receiving or is currently receiving antipyretic or analgesic medication on a daily or every other day basis from randomization through Day 7
* Has ever participated in an investigational study of a SARS-CoV-2 vaccine, a coronavirus vaccine, or an antiviral or other biologic product intended for the treatment of COVID-19.
* Has participated in another vaccine study within 3 months prior to screening or has participated in an investigational study within 4 weeks prior to the screening visit.
* Has ever received a vaccine based on vesicular stomatitis virus (VSV).
* Has a Fridericia's corrected time from Q wave to T wave (QTcF) interval \>470 msec (male) or \>480 msec (female), has a history of risk factors for Torsades de Pointes, or has uncorrected hypokalemia or hypomagnesemia.
* Is under the age of legal consent.
* Is smoking or vaping and/or has a history of chronic smoking or vaping within approximately six months prior to planned vaccination.
* Does not agree to follow the alcohol restrictions
* Has a tattoo, scar, or other physical finding at the area of the vaccination site that would interfere with intramuscular injection or a local tolerability assessment.
* Is a regular user of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year.
* Presents any concern by the investigator regarding safe participation in the study or for any other reason the investigator considers the participant inappropriate for participation in the study.
* Lives in a nursing home or long-term care facility.
* Is currently working in an occupation with high risk of exposure to SARS-CoV-2 (e.g., health care worker with direct patient contact, emergency response personnel).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Celerion ( Site 0002)

Tempe, Arizona, United States

Site Status

Clinical Pharmacology of Miami ( Site 0003)

Miami, Florida, United States

Site Status

QPS Miami Research Associates ( Site 0005)

South Miami, Florida, United States

Site Status

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

Springfield, Missouri, United States

Site Status

Celerion ( Site 0001)

Lincoln, Nebraska, United States

Site Status

Alliance for Multispecialty Reseach, LLC ( Site 0004)

Knoxville, Tennessee, United States

Site Status

Worldwide Clinical Trials ( Site 0007)

San Antonio, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 35809371 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34473343 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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V590-001

Identifier Type: OTHER

Identifier Source: secondary_id

V590-001

Identifier Type: -

Identifier Source: org_study_id