A Safety and Immunogenicity Study of Heterologous Prime-Boost Ebola Vaccine Regimens in Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Crucell Holland BV
ClinicalTrials.gov Identifier:
NCT02313077
First received: December 5, 2014
Last updated: April 11, 2016
Last verified: April 2016
  Purpose
The purpose of this study is to test the safety and immunogenicity of MVA-BN-Filo and Ad26.ZEBOV as heterologous prime-boost vaccine regimens in healthy adult participants.

Condition Intervention Phase
Healthy
Biological: MVA-BN-filo
Biological: Ad26. ZEBOV
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1, First-in-Human Study to Evaluate the Safety, Tolerability and Immunogenicity of Heterologous Prime-Boost Regimens Using MVA-BN®-Filo and Ad26.ZEBOV Administered in Different Sequences and Schedules in Healthy Adults

Resource links provided by NLM:


Further study details as provided by Crucell Holland BV:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: Up to 21 days after the 2nd vaccination (Day 36 for Group 5 or Day 50 for Groups 1 and 3 or Day 78 for Groups 2 and 4) ] [ Designated as safety issue: Yes ]
  • Number of participants with serious adverse events [ Time Frame: Up to the end of long-term follow-up (Day 360) ] [ Designated as safety issue: Yes ]
  • Number of participants with reactogenicity (ie, solicited local and systemic adverse events) [ Time Frame: Up to 1 week after each study vaccine administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immune responses to the study vaccine regimens as measured by a virus neutralization assay [ Time Frame: Groups 1 and 3:Day 1(pre-vaccination), 8, 29(pre-vaccination), 36, 50, 180, 240, 360; Groups 2 and 4:Day 1(pre-vaccination), 8, 29, 57(pre-vaccination), 64, 78, 180, 240, 360; Group 5:Day 1(pre-vaccination), 8, 15(pre-vaccination), 22, 36, 180, 240, 360 ] [ Designated as safety issue: No ]
  • Immune responses to the study vaccine regimens measured by an enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Groups 1 and 3:Day 1(pre-vaccination), 8, 29(pre-vaccination), 36, 50, 180, 240, 360; Groups 2 and 4:Day 1(pre-vaccination), 8, 29, 57(pre-vaccination), 64, 78, 180, 240, 360; Group 5:Day 1(pre-vaccination), 8, 15(pre-vaccination), 22, 36, 180, 240, 360 ] [ Designated as safety issue: No ]
  • Immune responses to the study vaccine regimens as measured by an enzyme-linked immunospot (ELISpot) assay [ Time Frame: Groups 1 and 3:Day 1(pre-vaccination), 8, 29(pre-vaccination), 36, 50, 180, 240, 360; Groups 2 and 4:Day 1(pre-vaccination), 8, 29, 57(pre-vaccination), 64, 78, 180, 240, 360; Group 5:Day 1(pre-vaccination), 8, 15(pre-vaccination), 22, 36, 180, 240, 360 ] [ Designated as safety issue: No ]

Enrollment: 87
Study Start Date: December 2014
Study Completion Date: March 2016
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Participants will receive MVA-BN-filo/ Ad26.ZEBOV (Day 1 /Day 29) or Placebo (Day 1/Day 29).
Biological: MVA-BN-filo
One 0.5 mL intramuscular (IM) injection of 1E8 (50%Tissue Culture Infectious Dose [TCID50]) on Day 1 (Groups 1 and 2), or on Day 29 (Group 3), or on Day 57 (Group 4), or on Day 15 (Group 5).
Biological: Ad26. ZEBOV
One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1 (Groups 3, 4 and 5), or on Day 29 (Group 1), or on Day 57 (Group 2).
Other: Placebo
One 0.5 mL IM injection of 0.9% saline on Day 1 and 29 (Groups 1 and 3), or on Day 1 and 57 (Groups 2 and 4).
Experimental: Group 2
Participants will receive MVA-BN-filo/Ad26.ZEBOV (Day 1 /Day 57) or placebo ( Day 1/Day 57).
Biological: MVA-BN-filo
One 0.5 mL intramuscular (IM) injection of 1E8 (50%Tissue Culture Infectious Dose [TCID50]) on Day 1 (Groups 1 and 2), or on Day 29 (Group 3), or on Day 57 (Group 4), or on Day 15 (Group 5).
Biological: Ad26. ZEBOV
One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1 (Groups 3, 4 and 5), or on Day 29 (Group 1), or on Day 57 (Group 2).
Other: Placebo
One 0.5 mL IM injection of 0.9% saline on Day 1 and 29 (Groups 1 and 3), or on Day 1 and 57 (Groups 2 and 4).
Experimental: Group 3
Participants will receive Ad26.ZEBOV/ MVA-BN-filo (Day 1/Day 29) or placebo (Day 1/Day 29).
Biological: MVA-BN-filo
One 0.5 mL intramuscular (IM) injection of 1E8 (50%Tissue Culture Infectious Dose [TCID50]) on Day 1 (Groups 1 and 2), or on Day 29 (Group 3), or on Day 57 (Group 4), or on Day 15 (Group 5).
Biological: Ad26. ZEBOV
One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1 (Groups 3, 4 and 5), or on Day 29 (Group 1), or on Day 57 (Group 2).
Other: Placebo
One 0.5 mL IM injection of 0.9% saline on Day 1 and 29 (Groups 1 and 3), or on Day 1 and 57 (Groups 2 and 4).
Experimental: Group 4
Participants will receive Ad26.ZEBOV/ MVA-BN-filo (Day 1/Day 57) or placebo (Day 1/Day 57).
Biological: MVA-BN-filo
One 0.5 mL intramuscular (IM) injection of 1E8 (50%Tissue Culture Infectious Dose [TCID50]) on Day 1 (Groups 1 and 2), or on Day 29 (Group 3), or on Day 57 (Group 4), or on Day 15 (Group 5).
Biological: Ad26. ZEBOV
One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1 (Groups 3, 4 and 5), or on Day 29 (Group 1), or on Day 57 (Group 2).
Other: Placebo
One 0.5 mL IM injection of 0.9% saline on Day 1 and 29 (Groups 1 and 3), or on Day 1 and 57 (Groups 2 and 4).
Experimental: Group 5
Participants will receive Ad26.ZEBOV/ MVA-BN-filo (Day 1/Day 15).
Biological: MVA-BN-filo
One 0.5 mL intramuscular (IM) injection of 1E8 (50%Tissue Culture Infectious Dose [TCID50]) on Day 1 (Groups 1 and 2), or on Day 29 (Group 3), or on Day 57 (Group 4), or on Day 15 (Group 5).
Biological: Ad26. ZEBOV
One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1 (Groups 3, 4 and 5), or on Day 29 (Group 1), or on Day 57 (Group 2).

Detailed Description:
This first-in-human study consists of 2 parts: 1) The main study, which is randomized, placebo-controlled, observer-blind; 2) A sub-study, which is open-label, uncontrolled, non-randomized study evaluating the safety, tolerability, and immunogenicity of MVA-BN-Filo and Ad26.ZEBOV administered in different sequences and schedules to healthy adult participants. The study consists of a Screening period (up to 28 days in the main study and up to 56 days in the sub-study), a vaccination period in which participants will be vaccinated at baseline (Day 1) followed by a boost on Day 15, 29 or 57, and a post-boost follow-up until all participants have had their 21-day post-boost visit (Day 36, 50 or Day 78). The total duration of the study will be about 1 year for participants who received vaccine and about 3 months for participants who received placebo. Safety will be monitored during the study.
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Must be healthy on the basis of physical examination, medical history, and the investigator's clinical judgment
  • Women of childbearing potential must have a negative serum β-human chorionic gonadotropin pregnancy test at screening, a negative urine pregnancy test immediately prior to each study vaccine administration, and practice adequate birth control measures from 28 days before the prime vaccination until at least 3 months after the boost vaccination as specified in the study protocol. If not heterosexually active at screening, must agree to practice adequate birth control measures if they become heterosexually active during their participation in the study (from screening onwards until at least 3 months after the boost vaccination). Agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction from screening onwards until at least 3 months after the boost vaccination
  • Women of non-childbearing potential, defined as postmenopausal (>45 years of age with amenorrhea for ≥2 years or any age with amenorrhea for ≥6 months and serum follicle-stimulating hormone [FSH] >40 mIU/mL) or surgically sterile (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), are not required to use the birth control methods as specified in the study protocol
  • A man who is sexually active with a woman of childbearing potential and who has not had a vasectomy must agree to use a double-barrier method of birth control, such as either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. In case the female partner is using an adequate method of birth control, a single-barrier method of birth control for the male subject is acceptable. Men must also agree not to donate sperm from screening onwards until at least 3 months after the boost vaccination
  • Must be available and willing to participate for the duration of the study visits and follow-up, provide verifiable identification, and have a means to be contacted

Exclusion Criteria:

  • Has been vaccinated with a candidate Ebola vaccine
  • Has been diagnosed with Ebola disease or exposed to Ebola including travel to West Africa in the last 12 months. West Africa includes but is not limited to the countries of Guinea, Liberia, Mali, and Sierra Leone
  • Has received any Ad26- or MVA-based candidate vaccine in the past
  • Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines), including known allergy to egg or aminoglycosides
  • A woman who is pregnant or breast-feeding, or planning to become pregnant while enrolled in the study or within 3 months after the boost vaccination
  • History of diabetes mellitus type 1 or type 2, including cases controlled with diet alone; thyroidectomy, or thyroid disease requiring medication during the last 12 months; uncontrolled hypertension as defined in the study protocol; or, major psychiatric illness and/or substance abuse problems during the past 12 months that in the opinion of the investigator would preclude participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02313077

Locations
United Kingdom
Oxford, United Kingdom
Sponsors and Collaborators
Crucell Holland BV
Investigators
Study Director: Crucell Holland BV Clinical Trial Crucell Holland BV
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Crucell Holland BV
ClinicalTrials.gov Identifier: NCT02313077     History of Changes
Other Study ID Numbers: CR106478  VAC52150EBL1001  2014-004883-39 
Study First Received: December 5, 2014
Last Updated: April 11, 2016
Health Authority: Great Britain: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Crucell Holland BV:
Healthy
Ebola viruses
Ebola Viral Disease (EVD)
Filoviruses
monovalent vaccine
Human adenovirus serotype 26 (Ad26) expressing the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV)
Modified Vaccinia Virus Ankara - Bavarian Nordic (MVA-BN) Filo-vector
Safety
Immunogenicity

ClinicalTrials.gov processed this record on July 28, 2016