Evaluation of the Safety and Immunogenicity of Three Consistency Lots and a High-Dose Lot of rVSV-ZEBOV-GP (V920 Ebola Vaccine) in Healthy Adults (V920-012)

• ClinicalTrials.gov Identifier: NCT02503202
• Recruitment Status: Completed
• First Posted: July 20, 2015
• Results First Posted: October 12, 2018
• Last Update Posted: October 12, 2018
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: July 17, 2015
• First Posted Date: July 20, 2015
• Results First Submitted Date: September 7, 2018
• Results First Posted Date: October 12, 2018
• Last Update Posted Date: October 12, 2018
• Actual Study Start Date: August 17, 2015
• Actual Primary Completion Date: May 2, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2018)

• Geometric Mean Titer of Anti-ZEBOV Glycoprotein Antibody [ Time Frame: Day 28 postvaccination ]
  Serum was collected for determination of geometric mean titer (GMT) of anti-Zaire ebolavirus envelope (ZEBOV) glycoprotein antibodies using an enzyme-linked immunosorbent assay (GP-ELISA). The unit of measure is ELISA units/mL (EU/mL). The lower limit of quantification for the assay was 36.11 EU/mL.
• Percentage of Participants Reporting Serious Adverse Events [ Time Frame: Up to Month 6 postvaccination ]
  An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. A serious AE (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is any other important medical event, is a cancer, or is associated with an overdose.
• Percentage of Participants With Injection-site Adverse Events Prompted on the Vaccination Report Card [ Time Frame: Up to Day 5 postvaccination ]
  An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Injection-site AEs prompted on the Vaccination Report Card (VRC) were erythema, pain, and swelling.
• Percentage of Participants With Elevated Maximum Temperature [ Time Frame: Up to Day 42 postvaccination ]
  Participants were instructed on the VRC to take and record their oral (or oral equivalent) temperature daily from the day of vaccination through Day 42. Elevated temperature was defined as ≥38.0° C (≥100.4° F).
• Percentage of Participants With Arthralgia or Arthritis Adverse Events Prompted on the Vaccination Report Card [ Time Frame: From Day 5 to Day 42 postvaccination ]
  An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Adverse events of arthralgia and arthritis were prompted on the VRC.
• Percentage of Participants With Rash Adverse Events Prompted on the Vaccination Report Card [ Time Frame: Up to Day 42 postvaccination ]
  An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Rash AEs prompted on the VRC were petechial rash, purpuric rash, and vesicular-type rash.
• Percentage of Participants With Vesicular Lesion Adverse Events Prompted on the Vaccination Report Card [ Time Frame: Up to Day 42 postvaccination ]
  An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Vesicular lesion AEs prompted on the VRC included blister and rash vesicular.

• Original Primary Outcome Measures (submitted: July 17, 2015): Geometric Mean Titer of anti-ZEBOV Glycoprotein Antibody [ Time Frame: Day 28 postvaccination ]
• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: July 17, 2015)

• Percentage of Participants Reporting Serious Adverse Experiences [ Time Frame: Up to Day 42 postvaccination ]
• Percentage of Participants with Vaccine Report Card (VRC)-prompted Injection-site Adverse Events [ Time Frame: Up to Day 5 postvaccination ]
• Percentage of Participants with VRC-prompted Elevated Temperature [ Time Frame: Up to Day 42 postvaccination ]
• Percentage of Participants with Arthralgia/Arthritis [ Time Frame: Day 5 through Day 42 postvaccination ]
• Percentage of Participants with Petechial/purpuric Rash [ Time Frame: Day 5 through Day 42 postvaccination ]
• Percentage of Participants with Vesicular Lesions [ Time Frame: Day 5 through Day 42 postvaccination ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of the Safety and Immunogenicity of Three Consistency Lots and a High-Dose Lot of rVSV-ZEBOV-GP (V920 Ebola Vaccine) in Healthy Adults (V920-012)
• Official Title: A Phase III, Randomized, Placebo-Controlled, Clinical Trial to Study the Safety and Immunogenicity of Three Consistency Lots and a High Dose Lot of rVSV-ZEBOV-GP (V920 Ebola Vaccine) in Healthy Adults
• Brief Summary: The study evaluated the safety and immunogenicity of 3 consistency lots and a high-dose lot of rVSV-ZEBOV-GP (V920 Ebola Vaccine) in healthy adults. The primary purpose of this study was to demonstrate consistency in the immune responses of participants receiving 3 separate lots of V920 through 28 days postvaccination. In addition to the 3 lot groups, a high-dose group and a placebo group were studied. A subset of participants representative of all treatment groups continued through 24 months postvaccination in the extension study for the evaluation of long-term safety. The primary hypothesis states that the geometric mean titer of anti-Zaire ebolavirus envelope (ZEBOV) glycoprotein antibody at 28 days postvaccination is equivalent across the three consistency lots.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Prevention of Ebola Infection

Intervention

• Biological: V920 Consistency Lot A
  V920 (rVSV-ZEBOV-GP) Ebola Zaire vaccine consistency Lot A, live, attenuated, sterile solution for intramuscular injection
• Biological: V920 Consistency Lot B
  V920 (rVSV-ZEBOV-GP) Ebola Zaire vaccine consistency Lot B, live, attenuated, sterile solution for intramuscular injection
• Biological: V920 Consistency Lot C
  V920 (rVSV-ZEBOV-GP) Ebola Zaire vaccine consistency Lot C, live, attenuated, sterile solution for intramuscular injection
• Biological: V920 High-dose Lot
  V920 (rVSV-ZEBOV-GP) Ebola Zaire vaccine high-dose lot, live, attenuated, sterile solution for intramuscular injection
• Biological: Placebo to V920
  Sodium chloride 0.9%, sterile solution for intramuscular injection

Study Arms

• Experimental: V920 Consistency Lot A
  Participants received a 1.0 mL intramuscular injection of V920 on Day 1
  Intervention: Biological: V920 Consistency Lot A
• Experimental: V920 Consistency Lot B
  Participants received a 1.0 mL intramuscular injection of V920 on Day 1
  Intervention: Biological: V920 Consistency Lot B
• Experimental: V920 Consistency Lot C
  Participants received a 1.0 mL intramuscular injection of V920 on Day 1
  Intervention: Biological: V920 Consistency Lot C
• Experimental: V920 High-dose Lot
  Participants received a 1.0 mL intramuscular injection of V920 on Day 1
  Intervention: Biological: V920 High-dose Lot
• Placebo Comparator: Placebo to V920
  Participants received a 1.0 mL intramuscular injection of placebo on Day 1
  Intervention: Biological: Placebo to V920

Publications *

• Halperin SA, Arribas JR, Rupp R, Andrews CP, Chu L, Das R, Simon JK, Onorato MT, Liu K, Martin J, Helmond FA; V920-012 Study Team. Six-Month Safety Data of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Envelope Glycoprotein Vaccine in a Phase 3 Double-Blind, Placebo-Controlled Randomized Study in Healthy Adults. J Infect Dis. 2017 Jun 15;215(12):1789-1798. doi: 10.1093/infdis/jix189.
• Grant-Klein RJ, Antonello J, Nichols R, Dubey S, Simon JK. Effects of Gamma Irradiation of Human Serum Samples from rVSVΔG-ZEBOV-GP (V920) Ebola Virus Vaccine Recipients on Plaque-Reduction Neutralization Assays. Am J Trop Med Hyg. 2021 Mar 29;104(5):1751-1754. doi: 10.4269/ajtmh.20-1055.
• Halperin SA, Das R, Onorato MT, Liu K, Martin J, Grant-Klein RJ, Nichols R, Coller BA, Helmond FA, Simon JK; V920-012 Study Team. Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults. J Infect Dis. 2019 Aug 30;220(7):1127-1135. doi: 10.1093/infdis/jiz241.
• Coller BG, Blue J, Das R, Dubey S, Finelli L, Gupta S, Helmond F, Grant-Klein RJ, Liu K, Simon J, Troth S, VanRheenen S, Waterbury J, Wivel A, Wolf J, Heppner DG, Kemp T, Nichols R, Monath TP. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic. Vaccine. 2017 Aug 16;35(35 Pt A):4465-4469. doi: 10.1016/j.vaccine.2017.05.097. Epub 2017 Jun 21.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 9, 2018): 1197
• Original Estimated Enrollment (submitted: July 17, 2015): 1125
• Actual Study Completion Date: September 29, 2017
• Actual Primary Completion Date: May 2, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Not of reproductive potential, or of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner for 2 months following study vaccination.

Exclusion Criteria:

• Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 90 days of participation in this trial.
• Has previously been randomized in another clinical trial and received V920 or any other Ebola vaccine.
• Has been exposed to Ebola virus at any time prior to study entry.
• Is pregnant or breastfeeding or plans to conceive within 2 months following study vaccination.
• Has direct household exposure to a pregnant or lactating woman at the time of participation in this trial.
• Has had a fever (≥100.5ºF/38.0ºC) within 48 hours prior to study entry.
• Has received systemic corticosteroids (equivalent of ≥2 mg/kg total daily dose of prednisone or ≥20 mg/day for persons weighing >10 kg) for ≥14 consecutive days and has not completed treatment at least 30 days prior to study entry.
• Has received systemic corticosteroids exceeding physiologic replacement doses (~5 mg/day prednisone equivalent) within 14 days prior to study entry.
• Has received any live virus vaccine within 30 days prior to study entry or any other (nonlive virus) vaccine within 14 days prior to study entry.
• Has known or suspected impairment of immunological function (e.g., HIV positive).
• Has direct household exposure to a person with known or suspected impairment of immunological function (e.g., HIV positive).
• Has a clinically significant history of intravenous (IV) drug abuse within 12 months prior to study entry.
• Has a known allergy/sensitivity or contraindication to investigational product(s) or its/their excipients (e.g., albumin).
• Has a history of malignancy <=5 years prior to study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Canada, Spain, United States

Administrative Information

• NCT Number: NCT02503202
• Other Study ID Numbers: V920-012; 2015-001658-14 ( EudraCT Number ); V920-012 ( Other Identifier: Merck Protocol Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Responsible Party: Merck Sharp & Dohme LLC
• Study Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: October 2018