A Study to Assess Safety, Tolerability, and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Participants (V591-001)

NCT04498247 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: V591-0012020-003493-46
• Study Type: interventional
• Target: 263
• Locations: 3 countries
• Sites: 9

Brief Summary

The primary objective of this early Phase 1/2 study is to identify the V591 dose that achieves the target immune response in humans based on preclinical or early clinical data.

Conditions

Coronavirus Disease (COVID-19)

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants With at Least One Solicited Injection Site Adverse Event (AE) After Any Study Intervention

  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. Injection site AEs of pain/tenderness, swelling, and redness/erythema were assessed.

  Up to 5 days after any study intervention

• Percentage of Participants With at Least One Solicited Systemic AE After Any Study Intervention

  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. Systemic AEs of fever, muscle pain, joint pain, headache, fatigue, rash, or nausea were assessed.

  Up to 14 days after any study intervention

• Percentage of Participants With at Least One Unsolicited Adverse Event After Any Study Intervention

  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. All unsolicited AEs were assessed.

  Up to 28 days after any study intervention

• Percentage of Participants With at Least 1 Serious Adverse Event

  An SAE is defined as any untoward medical occurrence that at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

  Up to 56 days after vaccination 1 and up to 122 days after vaccination 2 (up to 178 days)

• Percentage of Participants Who Discontinued Study Treatment Due to an 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.

  Up to 57 days

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

  A MAAE is defined as an adverse event 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.

  Up to 56 days after vaccination 1 and up to 122 days after vaccination 2 (up to 178 days)

Secondary Outcomes (4)

• Geometric Mean Titers for Serum Neutralizing Antibodies (nAb) as Measured by Pseudo-virus Neutralization Assay (PNA)

  Days 1, 15, 29, 57, 71, and 85

• Geometric Mean Concentration of Total Anti-Spike Immunoglobulin G (IgG) Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)

  Days 1, 15, 29, 57, 71, and 85

• Geometric Mean Fold Rise (GMFR) for Serum nAb as Measured by PNA

  Days 1, 15, 29, 57, 71, and 85

• Geometric Mean Fold Rise (GMFR) of Total Anti-Spike IgG Antibodies as Measured by ELISA

  Days 1, 15, 29, 57, 71, and 85

Study Arms (10)

Panel A

EXPERIMENTAL

Participants in this 18 to 55 year old sentinel cohort will receive 2 doses (Day 1 and Day 57) of 1x10\^5 50% tissue culture infectious dose (TCID50) V591 or placebo

Biological: V591; Other: Placebo

Panel B

EXPERIMENTAL

Participants in this 18 to 55 year old sentinel cohort will receive 2 doses (Days 1 and 57) of 1x10\^6 TCID50 V591 or placebo

Biological: V591; Other: Placebo

Panels C, G

EXPERIMENTAL

Participants in this 18 to 55 year old cohort (Panel C) or \>55 year old cohort (Panel G) will receive 1 dose of 1x10\^5 TCID50 V591 or placebo.

Biological: V591; Other: Placebo

Panels D, H

EXPERIMENTAL

Participants in this 18 to 55 year old cohort (Panel D) or \>55 year old cohort (Panel H) will receive 1 dose of 1x10\^6 TCID50 V591 or placebo.

Biological: V591; Other: Placebo

Panel E

EXPERIMENTAL

Participants in this 18 to 55 year old cohort will receive 1 dose of 1x10\^7 V591 or placebo.

Biological: V591; Other: Placebo

Panel F

EXPERIMENTAL

Participants in this 18 to 55 year old cohort will receive 2 doses (Days 1 and 169) of V591 or placebo. Day 1 will be 1x10\^4 TCID50 V591 or placebo and Day 169 will be 1x10\^5 TCID50 V591 or placebo.

Biological: V591; Other: Placebo

Panel I

EXPERIMENTAL

Participants in this \>55 year old cohort will receive 2 doses (Days 1 and 57) of 1x10\^5 TCID50 V591 or placebo

Biological: V591; Other: Placebo

Panel J

EXPERIMENTAL

Participants in this \>55 year old cohort will receive 2 doses (Days 1 and 57) of 1x10\^6 TCID50 V591 or placebo

Biological: V591; Other: Placebo

Panel K

EXPERIMENTAL

Participants in this \>55 year old cohort will receive 2 doses (Days 1 and 169) of 1x10\^5 TCID50 V591 or placebo

Biological: V591; Other: Placebo

Panel L

EXPERIMENTAL

Participants in this \>55 year old cohort will receive 2 doses (Days 1 and 169) of 1x10\^6 TCID50 V591 or placebo

Biological: V591; Other: Placebo

Interventions

V591 BIOLOGICAL

1 or 2 ascending doses of V591 will be administered via intramuscular (IM) injection.

Panel A; Panel B; Panel E; Panel F; Panel I; Panel J; Panel K; Panel L; Panels C, G; Panels D, H

Placebo OTHER

Placebo (0.9% sodium chloride) administered via IM injection.

Panel A; Panel B; Panel E; Panel F; Panel I; Panel J; Panel K; Panel L; Panels C, G; Panels D, H

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, electrocardiogram (ECG) and vital sign (VS) measurements performed prior to randomization.
• Is in overall good health based on laboratory safety tests obtained at the screening visit.
• Has been practicing social distancing for at least two weeks prior to planned Day 1 vaccination and has no close contacts with known active severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in that time period.
• Sentinel trial participants ONLY (Panel A, Panel B, and the first 5 participants of Panel E): Seronegative for SARS-COV-2.
• Is male or female, from 18 years to 55 years of age (inclusive) (Parts 1 and 2A) or \>55 years of age (Part 2B), at the time of providing documented informed consent.
• Male participants are eligible to participate if they agree to refrain from donating sperm during the intervention period and for at least 6 months after the last dose 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 .
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, is not a woman of childbearing potential (WOCBP) or Is a WOCBP and using an acceptable contraceptive method or be abstinent from heterosexual intercourse as their preferred and usual lifestyle.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Refrain from donating oocyte during the intervention period and for at least 6 months after the last dose of study intervention.
• The participant (or legally acceptable representative) has provided documented informed consent/assent for the study, including for future biomedical research.
• Is willing to comply with the study restrictions, including social distancing between screening and randomization.
• Is willing to abstain from donating whole blood or blood derivatives, tissue or organ all along the study.
• Agrees to provide study personnel with a primary telephone number as well as an alternate means of contact, if available (such as an alternate telephone number or email) for follow-up purposes.
• Can read, understand, and complete the Vaccination Report Card.

You may not qualify if:

• Is currently actively infected with SARS-CoV-2 (confirmed by polymerase chain reaction;\[PCR\]).
• Has prior medical history of confirmed SARS-CoV-2 infection or known exposure to an individual with confirmed coronavirus disease 2019 (COVID-19) disease or SARS CoV-2 infection within the past 2 weeks. With the exception of the sentinel participants (Panel A, Panel B, and the first 5 participants of Panel E), study participants will not be screened for enrollment by SARS-CoV-2 serology, allowing those who may have had a prior asymptomatic SARS-CoV-2 infection to be enrolled.
• Has a history of severe adverse reactions to vaccine administration, including anaphylaxis and related symptoms, such as urticaria, respiratory difficulty, angioedema and abdominal pain to vaccines, or history of known or suspected allergic reaction likely to be exacerbated by any component of the COVID-19 vaccine.
• Is currently (or highly suspected to be) immunocompromised, including anticipating the need for systemic immunosuppressive treatment within the next 6 months or 12 months for 2-dose Day 1, Day 169 panels or has been diagnosed or highly suspected as having a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition that could impact the immune response or the safety of the study vaccine.
• Has clinically significant 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 or presence of clinically significant pulmonary disorders (e.g. chronic obstructive pulmonary disease \[COPD\], etc.), or asthma.
• Has a history of confirmed SARS-CoV-1 or Middle Eastern respiratory syndrome (MERS)
• Has a history of or current clinically significant medical condition that puts or may put a participant at increased risk for severe SARS-CoV-2 disease, such as conditions associated with increased risk of severe illness from COVID-19, cancer, chronic kidney disease, COPD, immunocompromised state (weakened immune system) from solid organ transplant, obesity (BMI of 30 or higher), serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies, sickle cell disease, Type 2 diabetes mellitus, asthma, cerebrovascular disease, cystic fibrosis, hypertension or high blood pressure, an immunocompromised state (weakened immune system), neurologic conditions, such as dementia, liver disease, pregnancy, pulmonary fibrosis (having damaged or scarred lung tissues), smoking, thalassemia (a type of blood disorder), or Type 1 diabetes mellitus.
• Part 2B ONLY: Older adult participants having mild, well controlled hypertension as is widely characteristic of aging are allowed if their medication regimens have not substantively changed for the past 6 months, hypertension has not led to hospitalization or currently increased rate of clinic visits over the past year, and hypertension has not been confirmed as putting subjects at increased risk of severe illness from COVID-19 by the CDC (https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-risk.html).
• Is mentally or legally incapacitated, has significant emotional problems at the time of pre-study (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 any clinically significant major neurological disorders or seizures (including Guillain-Barré syndrome), with the exception of febrile seizures during childhood.
• Has a history of cancer (malignancy)
• Has a known or suspected history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or non-prescription drugs or food.
• Is positive for hepatitis B surface antigen (HBsAg), 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 undetectable and there is no evidence of or history of liver disease.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (9)

Research Centers of America, LLC ( Site 0014)

Hollywood, Florida, 33024, United States

Location

Alliance for Multispecialty Research, LLC ( Site 0013)

Wichita, Kansas, 67205, United States

Location

Central Kentucky Research Associates, Inc. ( Site 0011)

Lexington, Kentucky, 40509, United States

Location

The Center for Pharmaceutical Research PC ( Site 0012)

Kansas City, Missouri, 64114, United States

Location

SCRI-CCCIT GesmbH ( Site 0006)

Salzburg, 5020, Austria

Location

Medizinische Universitaet Wien ( Site 0007)

Vienna, 1090, Austria

Location

Universitair Ziekenhuis Gent ( Site 0003)

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

SGS Life Science Services ( Site 0001)

Antwerp, 2060, Belgium

Location

ATC - Clinical Pharmacology Unit ( Site 0002)

Liège, 4000, Belgium

Location

Related Publications (1)

• Vanhoutte F, Liu W, Wiedmann RT, Haspeslagh L, Cao X, Boundy K, Aliprantis A, Davila M, Hartzel J, Li J, McGuire M, Ramsauer K, Tomberger Y, Tschismarov R, Brown DD, Xu W, Sachs JR, Russell K, Stoch SA, Lai E. Safety and immunogenicity of the measles vector-based SARS-CoV-2 vaccine candidate, V591, in adults: results from a phase 1/2 randomised, double-blind, placebo-controlled, dose-ranging trial. EBioMedicine. 2022 Jan;75:103811. doi: 10.1016/j.ebiom.2021.103811. Epub 2022 Jan 15.

  PMID: 35042081 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 indicating that V591 was not predicted to provide adequate protection against disease caused by SARS-CoV-2.

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 4, 2020
• Study Start: August 27, 2020
• Primary Completion: March 5, 2021
• Study Completion: March 5, 2021
• Last Updated: December 23, 2021
• Results First Posted: December 23, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); US (4); BE (3)