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The purpose of this phase 3 multicenter, randomized, double-blind, placebo-controlled rollover study is to evaluate the safety and long-term immunogenicity of CHIKV VLP vaccine in adult and adolescent participants and to evaluate CHIKV VLP booster vaccine induced serum neutralizing antibody (SNA) response at 3, 4, or 5 years post-initial CHIKV VLP vaccination.
Primary Objectives:
Secondary Objectives:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1a | Active Comparator | CHIKV VLP vaccine booster, 3 years post initial vaccination |
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| Group 1b | Placebo Comparator | Placebo booster, 3 years post initial vaccination |
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| Group 2a | Active Comparator | CHIKV VLP vaccine booster, 4 years post initial vaccination |
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| Group 2b | Placebo Comparator | Placebo booster, 4 years post initial vaccination |
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| Group 3a | Active Comparator | CHIKV VLP vaccine booster, 5 years post initial vaccination |
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| Group 3b | Placebo Comparator | Placebo booster, 5 years post initial vaccination |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CHIKV VLP vaccine booster | Biological | CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP) 40mg, aluminum hydroxide 2% adjuvant, and formulation buffer supplied as a single dose of 0.8 mL in a pre-filled syringe, to be administered via intramuscular (IM) injection in the deltoid muscle. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants maintaining a preboost anti-CHIKV SNA titer ≥100 at yearly intervals up to 5 years post-initial vaccination | For all groups using the immunogenicity evaluable population (IEP) the proportion of participants maintaining a preboost anti-CHIKV SNA titer ≥100 (seroresponse rate, also considered the presumptive seroprotection rate) at yearly intervals up to 5 years post-initial vaccination in one of the feeder studies; only prebooster data will be summarized. | 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV317-005 until booster |
| Proportion of vaccine boosted participants with composite booster response at 21 days after booster vaccination | For IEP participants who receive a CHIKV VLP vaccine booster (Groups 1a, 2a, and 3a), proportion of participants with a boost response is defined as a composite of:
Note: Prebooster is the last SNA sample prior to booster dose, ideally the sample on boost day prior to booster dose administration but can be the time point prior if the boost day sample is missed or incorrectly processed. | 21 days after booster vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| Anti-CHIKV SNA Geometric Mean Titers (GMTs) at yearly intervals | For all groups using the IEP, anti-CHIKV SNA GMTs preboost at yearly intervals up to 5 years post-initial CHIKV VLP vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005; only prebooster data will be summarized. | 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005 until booster |
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Inclusion Criteria:
Additional inclusion criteria to be assessed at Prerandomization Visit (Visit 5), before Randomization A (Visit 6), and before Randomization B (Visit 8 for Group 2 and Visit 10 for Group 3) to determine eligibility for a booster dose of CHIKV VLP vaccine or placebo:
- Women who are either: i. Not of childbearing potential (CBP): premenarche, surgically sterile (at least six weeks postbilateral tubal ligation or bilateral total salpingectomy, bilateral oophorectomy, or hysterectomy), or postmenopausal (defined as a history of ≥12 consecutive months without menses prior to randomization in the absence of other pathologic or physiologic causes, following cessation of exogenous sex-hormonal treatment). For women who are postmenopausal, documented follicle stimulating hormone (FSH) level of ≥40 mIU/mL must be obtained. If the FSH is <40 mIU/mL, the participant must agree to use an acceptable form of contraception. or: ii. Meet all the below criteria:
Women participants of CBP must use an acceptable method of contraception from ≥30 days prior to Randomization A or assignment to Group 1; those who are randomized to Groups 2 or 3 at year 3 can discontinue contraception until 30 days prior to booster dose administration, if desired. Women participants of CBP must use an acceptable method of contraception from ≥30 days prior to Randomization B through six-months postbooster vaccination dose (if applicable).
Note: Contraception requirements do not apply for participants in exclusively same-sex relationships and these participants should have no plans to become pregnant by any other means during the same time period as women of CBP are required to use contraception. Contraception requirements do not apply to Group 4 participants (unrandomized or unboosted).
Exclusion Criteria:
Additional exclusion criteria to be assessed at Prerandomization Visit (Visit 5), before Randomization A (Visit 6), and before Randomization B (Visit 8 for Group 2 and Visit 10 for Group 3) to determine eligibility for a booster dose of CHIKV VLP vaccine or placebo:
Group 1: 30 days prior to Randomization A or assignment to Group 1 at Visit 6 through Visit 7 Group 2: 30 days prior to Randomization A at Visit 6 until the Randomization A visit and 30 days prior to booster dose at Visit 8 through Visit 9 Group 3: 30 days prior to Randomization A at Visit 6 until the Randomization A visit and 30 days prior to booster dose at Visit 10 through EOS Visit Group 4: 30 days prior to Randomization A at Visit 6 until the Randomization A visit Note: Participation in an observational trial or follow-up phase of a trial may be allowed; however, these instances should be discussed with this study's medical monitor (MM).
Note: Participants that are ineligible or decline booster will be included in Group 4 (unrandomized or unboosted) for follow-up unless consent/assent for follow-up is withdrawn.
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Ajiboye, MD | Bavarian Nordic | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alliance for Multispecialty Research, LLC | Mobile | Alabama | 36608 | United States | ||
| Alliance for Multispecialty Research, LLC |
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All eligible participants in the youngest (12 to <18 years) and oldest 2 (≥65 years) age groups will be assigned to a booster at Year 3 (Group 1). All other participants will be randomized 1:1:1 to a booster at Year 3 (Group 1), 4 (Group 2), or 5 (Group 3). Prior to booster dose administration participants will be randomized 1:1 to CHIKV VLP vaccine booster or placebo booster.
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Participants, care providers, and investigator will not be blinded for the timing of when the participant will receive the vaccine booster or placebo booster. They will be blinded to all booster treatment assignments (vaccine booster or placebo booster).
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| Group 4 | No Intervention | Unrandomized or unboosted participants, for any reason |
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| Placebo booster | Biological | Placebo is comprised of formulation buffer supplied as a single dose of 0.8 mL in a pre-filled syringe administered via IM injection in the deltoid muscle. |
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| Anti-CHIKV SNA GMTs at 21 days postboost | Anti-CHIKV SNA GMTs in Groups 1a, 2a, and 3a (PXVX0317 IEP booster population), at 21 days postboost. | 21 days postboost for Groups 1a, 2a, and 3a |
| Anti-CHIKV SNA Geometric Mean Fold Increase (GMFI) Prebooster to Postbooster | For IEP participants who receive a CHIKV VLP vaccine booster (Groups 1a, 2a, and 3a) and have a 21-day postbooster SNA titer, GMFI from prebooster anti-CHIKV SNA titer to 21 days postbooster anti-CHIKV SNA titer and at yearly intervals up to 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005. | 21 days after booster vaccination and 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005 |
| Booster Response at 21 Days Relative to 21-day Response in Feeder Study EBSI-CV-317-004 or EBSI-CV-317-005 | For IEP participants who receive a CHIKV VLP vaccine booster (Groups 1a, 2a, and 3a) and have a 21-day postboost SNA titer, GMFI from feeder study EBSI-CV-317-004 or EBSI-CV-317-005 Day 22 SNA titer to 21-day postbooster SNA titer in the rollover study. | 21 days after booster vaccination |
| Tempe |
| Arizona |
| 85281 |
| United States |
| Optimal Research, LLC | Melbourne | Florida | 32934 | United States |
| Suncoast Research Associates, LLC | Miami | Florida | 33173 | United States |
| Synexus Clinical Research US, Inc. | Chicago | Illinois | 60602 | United States |
| Optimal Research, LLC | Peoria | Illinois | 61614 | United States |
| Alliance for Multispecialty Research, LLC | Newton | Kansas | 67114 | United States |
| Alliance for Multispecialty Research, LLC | Wichita | Kansas | 67207 | United States |
| Alliance for Multispecialty Research, LLC | Lexington | Kentucky | 40509 | United States |
| Alliance for Multispecialty Research, LLC | Kansas City | Missouri | 64114 | United States |
| Wr-Crcn, Llc | Las Vegas | Nevada | 89106 | United States |
| Alliance for Multispecialty Research, LLC | Las Vegas | Nevada | 89119 | United States |
| Rochester Clinical Research, LLC | Rochester | New York | 14609 | United States |
| M3 Wake Research Inc. | Raleigh | North Carolina | 27612 | United States |
| Velocity Clinical Research, Cleveland | Cleveland | Ohio | 44122 | United States |
| Lynn Institute of Norman | Norman | Oklahoma | 73072 | United States |
| Velocity Clinical Research, Medford | Medford | Oregon | 97504 | United States |
| Velocity Clinical Research, Providence | East Greenwich | Rhode Island | 02818 | United States |
| Velocity Clinical Research, Austin | Cedar Park | Texas | 78613 | United States |
| DM Clinical Research | Houston | Texas | 77081 | United States |
| BFHC Research, LLC | San Antonio | Texas | 78249 | United States |
| DM Clinical Research | Tomball | Texas | 77375 | United States |
| Velocity Clinical Research, Salt Lake City | West Jordan | Utah | 84088 | United States |
| Alliance for Multispecialty Research, LLC | Norfolk | Virginia | 23502 | United States |
| ID | Term |
|---|---|
| D065632 | Chikungunya Fever |
| ID | Term |
|---|---|
| D018354 | Alphavirus Infections |
| D001102 | Arbovirus Infections |
| D000079426 | Vector Borne Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D014777 | Virus Diseases |
| D014036 | Togaviridae Infections |
| D012327 | RNA Virus Infections |
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