Clinical trial NCT04569786: Dose Ranging Trial to Assess Safety and Immunogenicity of V590 (COVID-19 Vaccine) in Healthy Adults (V590-001)
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Safety and Immunogenicity of V590 in Healthy Adults
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Coronavirus Disease (COVID-19)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-09-30
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of Participants With at Least 1 Solicited Injection Site Adverse Event
timeFrame: Up to 5 days post-vaccination
measure: Percentage of Participants With at Least 1 Solicited Systemic Adverse Event
timeFrame: Up to 28 days post-vaccination
measure: Percentage of Participants With at Least 1 Unsolicited Adverse Event
timeFrame: Up to ~28 days post-vaccination
measure: Percentage of Participants With at Least 1 Medically Attended Adverse Event
timeFrame: Up to 28 days post-vaccination
measure: Percentage of Participants With at Least 1 Serious Adverse Event
timeFrame: Active monitoring through Day 28 post-vaccination (Up to a maximum of ~90 days post-vaccination)
measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by Plaque Reduction Neutralization Test
timeFrame: 28 days post-vaccination
Secondary outcomes:
measure: Geometric Mean Titers for SNAs as Measured by PRNT- 7 Days
timeFrame: 7 days post-vaccination
measure: Geometric Mean Titers for SNAs as Measured by PRNT- 14 Days
timeFrame: 14 days post vaccination
measure: Geometric Mean Titers for Total Anti-Spike Immunoglobulin G Antibodies as Measured by Enzyme-Linked Immunosorbent Assay
timeFrame: 7, 14, and 28 days post vaccination
measure: Number of Participants With Vaccine Viremia as Measured by Reverse Transcription-Polymerase Chain Reaction
timeFrame: 1, 2, 3, 4, 5, 6, 7, 14 and 28 days post-vaccination
measure: Number of Participants With Viral Shedding in Saliva as Measured by RT-PCR
timeFrame: 1, 2, 3, 4, 5, 6, 7, 14, and 28 days post-vaccination
measure: Number of Participants With Viral Shedding in Urine as Measured by RT-PCR
timeFrame: 1, 2, 3, 4, 5, 6, 7, 14, and 28 days post-vaccination
measure: Number of Participants With Viral Shedding in Stool (If Assayed) as Measured by RT-PCR
timeFrame: 2-4, 5-7 days post-vaccination
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion ( Site 0002)
state: Arizona
city: Miami
country: United States
facility: Clinical Pharmacology of Miami ( Site 0003)
state: Florida
city: South Miami
country: United States
facility: QPS Miami Research Associates ( Site 0005)
state: Florida
city: Springfield
country: United States
facility: Bio-Kinetic Clinical Applications (QPS) ( Site 0006)
state: Missouri
city: Lincoln
country: United States
facility: Celerion ( Site 0001)
state: Nebraska
city: Knoxville
country: United States
facility: Alliance for Multispecialty Reseach, LLC ( Site 0004)
state: Tennessee
city: San Antonio
country: United States
facility: Worldwide Clinical Trials ( Site 0007)
state: Texas
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.