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Clinical Trial Results:
A Phase 3 Safety, Immunogenicity, and Lot-Consistency Trial of the VLP-Based Chikungunya Vaccine PXVX0317 in Healthy Adults and Adolescents

Summary
EudraCT number	2023-001124-42
Trial protocol	Outside EU/EEA
Global end of trial date	03 Apr 2023

Results information
Results version number	v1(current)
This version publication date	19 Apr 2024
First version publication date	19 Apr 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

EBSICV317004

ISRCTN number

US NCT number

NCT05072080

WHO universal trial number (UTN)

Sponsor organisation name

Bavarian Nordic A/S

Sponsor organisation address

Philip Heymans Alle 3, Hellerup, Denmark, 2900

Public contact

Medical Information, Bavarian Nordic A/S, medical.information_eu@bavarian-nordic.com

Scientific contact

Medical Information, Bavarian Nordic A/S, medical.information_eu@bavarian-nordic.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002656-PIP01-19

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

02 Feb 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Apr 2023

Was the trial ended prematurely?

Main objective of the trial

Coprimary Objectives: 1. To evaluate the safety of PXVX0317 (CHIKV VLP vaccine) in healthy adult and adolescent participants 12 to <65 years of age. 2. To compare the anti-CHIKV serum neutralising antibody (SNA) response to PXVX0317 (CHIKV VLP vaccine) and placebo at Day 22, as measured by geometric mean titre (GMT) and clinically relevant difference in seroresponse rate (PXVX0317 minus placebo). 3. To demonstrate the consistency of the anti-CHIKV SNA response across three consecutively manufactured lots of PXVX0317 (CHIKV VLP vaccine) at Day 22 as measured by GMT.

Protection of trial subjects

Study documents and participant facing documents including recruiting materials were reviewed and approved by an Institutional Review Board (IRB) before enrolment of participants in the study and prior to implementation. All study participants were required to read and sign an Informed Consent Form. Assent was also obtained from the study participant where required. Participants were monitored by study staff for signs of an acute adverse reaction(s) for 30 minutes after injection of IP. Vital signs were taken before and after study vaccine administration. Reactogenicity/solicited adverse events were collected from Day 1 (administration of IP) through Day 8. Unsolicited AEs were collected from Day 1 through Day 29. Serious adverse events, adverse events of special interest (defined as the occurrence of new onset or worsening arthralgia that was medically attended), and medically attended adverse events (defined as medically attended visits and included hospital, emergency room, urgent care clinic, or other visits to or from medical personnel) were collected from Day 1 through the Day 183 EOS. A planned independent Safety Monitoring Committee (SMC) blinded safety data review was conducted after the first 300 participants completed the Day 29 Visit and a second blinded SMC safety data review was conducted after the last participant completed the Day 29 visit.

Background therapy

N/A

Evidence for comparator

N/A - Placebo

Actual start date of recruitment

29 Sep 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 3258

Worldwide total number of subjects

3258

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

254

Adults (18-64 years)

3004

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was a multicenter study conducted in the United States, using 47 sites. Healthy participants were enroled in this study. Recruitment Period was from 29Sep2021 to 06Oct2022.

Screening details

A total of 4215 participants were screened. Screening window was no greater than 30 days prior to Day 1. Rescreening was permissible. Eligibility data was collected including medical history, concomitant therapy, viral screening, vital signs, physical exams, and urine pregnancy tests. Informed consent or informed consent with assent was obtained.

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

Use of a standardised pre-filled syringe and injection volume for all injections. All syringes had a semi-transparent barrel cover to mask any difference in appearance between placebo and CHIKV VLP vaccine. No sponsor personnel had access to the randomisation schedule. No site personnel had access to treatment assignments. Assays were run in a blinded manner. The assay titre results were not delivered to the sponsor data management and analysis team until after database lock.

Are arms mutually exclusive

Group 1 - PXVX0317 Lot 104

Arm description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 104 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Arm type

Experimental

Investigational medicinal product name

CHIKV VLP Vaccine

Investigational medicinal product code

PXVX0317

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

CHIKV VLP vaccine (PXVX0317) is comprised of CHIKV VLP 40 µg with 300 µg aluminum hydroxide 2%. Participants received CHIKV VLP vaccine on Day 1 by intramuscular injection in the deltoid muscle. The CHIKV VLP vaccine was supplied as a single dose 0.8 mL pre-filled syringe. The injection was to be administered within 2 hours of removal of the pre-filled syringe from 2 to 8°C storage.

Group 2 - PXVX0317 Lot 105

Arm description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 105 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Arm type

Experimental

Investigational medicinal product name

CHIKV VLP Vaccine

Investigational medicinal product code

PXVX0317

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Group 3 - PXVX0317 Lot 106

Arm description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 106 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Arm type

Experimental

Investigational medicinal product name

CHIKV VLP Vaccine

Investigational medicinal product code

PXVX0317

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Group 4 - Placebo

Arm description

Biological/Vaccine: Placebo Placebo is comprised of formulation buffer

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo is a sterile aqueous solution with the same excipient composition as the drug product without CHIKV VLP and aluminum hydroxide adjuvant. Participants received placebo on Day 1 by intramuscular injection in the deltoid muscle. Placebo was supplied as a single dose 0.8 mL pre-filled syringe. The injection was to be administered within 2 hours of removal of the pre-filled syringe from 2 to 8°C storage.

Pooled PXVX0317

Arm description

Arm created for reporting results purposes only. Includes all participants in Group 1 (PXVX0317 Lot 104) + Group 2 (PXVX0317 Lot 105) + Group 3 (PXVX0317 Lot 106).

Arm type

Experimental

Investigational medicinal product name

CHIKV VLP Vaccine

Investigational medicinal product code

PXVX0317

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 1	Group 1 - PXVX0317 Lot 104	Group 2 - PXVX0317 Lot 105	Group 3 - PXVX0317 Lot 106	Group 4 - Placebo	Pooled PXVX0317
Started	919	948	927	464	2794
Completed	803	837	832	430	2472
Not completed	116	111	95	34	322
Withdrawal by parent	-	-	1	-	1
Consent withdrawn by subject	45	30	27	7	102
Physician decision	2	1	1	-	4
Subject incarcerated	-	1	-	1	1
Subject missed last visit (Day 183)	3	1	1	-	5
Subject left site without receiving dose	-	1	-	-	1
Death	-	-	1	-	1
Noncompliance (protocol, visits, ediary, etc	-	2	1	1	3
Subject was deployed	-	1	-	-	1
Subject moved	1	3	5	2	9
Lost to follow-up	65	70	58	23	193
Sponsor decision	-	1	-	-	1

Baseline characteristics

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Reporting group title

Group 1 - PXVX0317 Lot 104

Reporting group description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 104 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Reporting group title

Group 2 - PXVX0317 Lot 105

Reporting group description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 105 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Reporting group title

Group 3 - PXVX0317 Lot 106

Reporting group description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 106 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Reporting group title

Group 4 - Placebo

Reporting group description

Biological/Vaccine: Placebo Placebo is comprised of formulation buffer

Reporting group title

Pooled PXVX0317

Reporting group description

Arm created for reporting results purposes only. Includes all participants in Group 1 (PXVX0317 Lot 104) + Group 2 (PXVX0317 Lot 105) + Group 3 (PXVX0317 Lot 106).

Reporting group values	Group 1 - PXVX0317 Lot 104	Group 2 - PXVX0317 Lot 105	Group 3 - PXVX0317 Lot 106	Group 4 - Placebo	Pooled PXVX0317	Total
Number of subjects	919	948	927	464	2794	3258
Age categorical
Units: Subjects
Adolescents (12-17 years)	67	76	74	37	217	254
Adults (18-64 years)	852	872	853	427	2577	3004
Age continuous
Units: years
arithmetic mean (standard deviation)	39 ( 14.4 )	38 ( 14.3 )	39 ( 14.0 )	39 ( 14.4 )	39 ( 14.3 )	-
Gender categorical
Units: Subjects
Female	452	506	478	231	1436	1667
Male	467	442	449	233	1358	1591
Ethnicity
Units: Subjects
Hispanic or Latino	165	166	175	71	506	577
Not Hispanic or Latino	735	760	731	379	2226	2605
Not Reported	18	22	21	14	61	75
Unknown	1	0	0	0	1	1
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	11	6	13	2	30	32
Asian	26	30	23	16	79	95
Native Hawaiian or Other Pacific Islander	2	4	0	4	6	10
Black or African American	190	175	169	89	534	623
White	663	693	687	341	2043	2384
More than one race	23	32	23	8	78	86
Unknown or Not Reported	4	8	12	4	24	28
Baseline Anti-CHIKV SNA Serostatus
LLOQ = lower limit of quantitation.
Units: Subjects
Negative (<LLOQ)	894	925	906	458	2725	3183
Positive (>=LLOQ)	24	18	21	6	63	69
Missing	1	5	0	0	6	6
Height
Units: cm
arithmetic mean (standard deviation)	171.4 ( 10.03 )	170.4 ( 9.55 )	170.7 ( 10.02 )	171.2 ( 9.97 )	170.8 ( 9.87 )	-
Weight
Units: kg
arithmetic mean (standard deviation)	78.5 ( 16.50 )	78.4 ( 16.08 )	78.3 ( 16.42 )	77.6 ( 16.42 )	78.4 ( 16.33 )	-
Body mass index (BMI)
Units: kg/m^2
arithmetic mean (standard deviation)	26.63 ( 4.579 )	26.89 ( 4.480 )	26.73 ( 4.499 )	26.38 ( 4.570 )	26.75 ( 4.519 )	-

End points

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Reporting group title

Group 1 - PXVX0317 Lot 104

Reporting group description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 104 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Reporting group title

Group 2 - PXVX0317 Lot 105

Reporting group description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 105 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Reporting group title

Group 3 - PXVX0317 Lot 106

Reporting group description

Biological/Vaccine: CHIKV VLP/adjuvant - Lot 106 CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

Reporting group title

Group 4 - Placebo

Reporting group description

Biological/Vaccine: Placebo Placebo is comprised of formulation buffer

Reporting group title

Pooled PXVX0317

Reporting group description

Arm created for reporting results purposes only. Includes all participants in Group 1 (PXVX0317 Lot 104) + Group 2 (PXVX0317 Lot 105) + Group 3 (PXVX0317 Lot 106).

Primary: Incidence of solicited Adverse Events (AE)

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End point title

Incidence of solicited Adverse Events (AE) ^[1]

End point description

Incidence of solicited AEs through Day 8 for PXVX0317 (CHIKV VLP Vaccine) and placebo for all age strata combined (safety population). Number of subjects analysed is number of safety population participants who completed a memory aid following the vaccination.

End point type

Primary

End point timeframe

7 days post-vaccination

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses does not apply to this endpoint. Endpoint is reporting a count of subjects that reported a solicited adverse event.

End point values	Group 1 - PXVX0317 Lot 104	Group 2 - PXVX0317 Lot 105	Group 3 - PXVX0317 Lot 106	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	906	939	920	458	2765
Units: Subjects	319	373	366	124	1058

No statistical analyses for this end point

Primary: Incidence of unsolicited AEs

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End point title

Incidence of unsolicited AEs ^[2]

End point description

Incidence of unsolicited AEs through Day 29 for PXVX0317 (CHIKV VLP Vaccine) and placebo for all age strata combined (safety population). Analysis population: Safety Population (vaccinated participants who provided safety assessment data), all ages pooled

End point type

Primary

End point timeframe

28 days post-vaccination

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses does not apply to this endpoint. Endpoint is reporting a count of subjects that reported an unsolicited adverse event.

End point values	Group 1 - PXVX0317 Lot 104	Group 2 - PXVX0317 Lot 105	Group 3 - PXVX0317 Lot 106	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	918	945	927	464	2790
Units: Subjects	139	146	155	62	440

No statistical analyses for this end point

Primary: Incidence of Adverse Events of Special Interest (AESI)

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End point title

Incidence of Adverse Events of Special Interest (AESI) ^[3]

End point description

Incidence of AESIs, through Day 183 for PXVX0317 (CHIKV VLP Vaccine) and placebo for all age strata combined (safety population). Adverse events of special interest (AESI) were defined as the occurrence of new onset or worsening arthralgia that was medically attended. Analysis population: Safety Population (vaccinated participants who provided safety assessment data), all ages pooled

End point type

Primary

End point timeframe

182 days post-vaccination

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses does not apply to this endpoint. Endpoint is reporting a count of subjects that reported an adverse event of special interest (AESI).

End point values	Group 1 - PXVX0317 Lot 104	Group 2 - PXVX0317 Lot 105	Group 3 - PXVX0317 Lot 106	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	918	945	927	464	2790
Units: Subjects	3	2	1	1	6

No statistical analyses for this end point

Primary: Incidence of Medically Attended Adverse Event (MAAE)

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End point title

Incidence of Medically Attended Adverse Event (MAAE) ^[4]

End point description

Incidence of MAAEs through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population). Medically attended adverse events (MAAE) were defined as medically attended visits and included hospital, emergency room, urgent care clinic, or other visits to or from medical personnel. Analysis population: Safety Population (vaccinated participants who provided safety assessment data), all ages pooled.

End point type

Primary

End point timeframe

182 days post-vaccination

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses does not apply to this endpoint. Endpoint is reporting a count of subjects that reported a medically attended adverse event (MAAE).

End point values	Group 1 - PXVX0317 Lot 104	Group 2 - PXVX0317 Lot 105	Group 3 - PXVX0317 Lot 106	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	918	945	927	464	2790
Units: Subjects	81	83	85	42	249

No statistical analyses for this end point

Primary: Incidence of Serious Adverse Event (SAE)

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End point title

Incidence of Serious Adverse Event (SAE) ^[5]

End point description

Incidence of SAEs through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population). Analysis population: Safety Population (vaccinated participants who provided safety assessment data), all ages pooled.

End point type

Primary

End point timeframe

182 days post-vaccination

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses does not apply to this endpoint. Endpoint is reporting a count of subjects that reported a serious adverse event.

End point values	Group 1 - PXVX0317 Lot 104	Group 2 - PXVX0317 Lot 105	Group 3 - PXVX0317 Lot 106	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	918	945	927	464	2790
Units: Subjects	10	7	6	1	23

No statistical analyses for this end point

Primary: Anti-CHIKV serum neutralising antibody (SNA) seroresponse rates at Day 22

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End point title

Anti-CHIKV serum neutralising antibody (SNA) seroresponse rates at Day 22 ^[6]

End point description

Anti-CHIKV SNA seroresponse rates for PXVX0317 (CHIKV VLP vaccine) and placebo, difference (PXVX0317 minus placebo), and associated 95% confidence interval (CI) at Day 22 for the immunogenicity evaluable population (IEP), all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding.

End point type

Primary

End point timeframe

21 days post-vaccination

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	424	2559
Units: percentage of participants
number (confidence interval 95%)	1.2 (0.5 to 2.7)	97.8 (97.2 to 98.3)

Anti-CHIKV SNA seroresponse rates at Day 22

Statistical analysis description

Anti-CHIKV serum neutralising antibody (SNA) seroresponse rates at Day 22. Seroresponse rate difference is (PXVX0317 minus placebo). All 3 coprimary endpoints were required to be met for success, so no multiple comparisons were performed.

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2983

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[7]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

96.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

97.5

Notes
[7] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Primary: Anti-CHIKV SNA geometric mean titres (GMT) at Day 22

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End point title

Anti-CHIKV SNA geometric mean titres (GMT) at Day 22 ^[8]

End point description

Anti-CHIKV SNA GMTs and associated 95% CIs at Day 22 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding.

End point type

Primary

End point timeframe

21 days post-vaccination

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	424	2559
Units: Titre
geometric mean (confidence interval 95%)	8 (7 to 9)	1618 (1522 to 1720)

Anti-CHIKV SNA Geometric Mean Titres at Day 22

Statistical analysis description

Anti-CHIKV SNA Geometric Mean Titres (GMT) at Day 22. All 3 coprimary endpoints were required to be met for success, so no multiple comparisons were performed. Ratio of GMTs is (PXVX0317:placebo).

Comparison groups

Pooled PXVX0317 v Group 4 - Placebo

Number of subjects included in analysis

2983

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[9]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

206

Confidence interval

level

95%

sides

2-sided

lower limit

183

upper limit

232

Notes
[9] - ANOVA model includes site and treatment group as fixed effects, assuming normality of log titres. P-value tests equivalence of group GMTs on log scale.

Primary: Anti-CHIKV SNA GMT ratios between pairs of PXVX0317 (CHIKV VLP vaccine) lots at Day 22

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End point title

Anti-CHIKV SNA GMT ratios between pairs of PXVX0317 (CHIKV VLP vaccine) lots at Day 22 ^[10]

End point description

Anti-CHIKV SNA GMT ratios and associated 95% CIs between all three pairs of PXVX0317 (CHIKV VLP vaccine) lots (104:105, 104:106, 105:106) in adults 18 to <46 years of age in the IEP at Day 22. Analysis population was adults 18 to <46 years in the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding.

End point type

Primary

End point timeframe

21 days post-vaccination

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint does not apply to all arms in the study. Endpoint only applies to Group 1, Group 2, and Group 3, as these are the arms in which participants received one of the three consecutively manufactured lots of CHIKV-VLP vaccine. Endpoint is reporting ratios between pairs of these CHIKV-VLP vaccine lots (Group 1:Group 2, Group 1:Group 3, and Group 2:Group 3).

End point values	Group 1 - PXVX0317 Lot 104	Group 2 - PXVX0317 Lot 105	Group 3 - PXVX0317 Lot 106
Number of subjects analysed	488	498	494
Units: Titre
geometric mean (confidence interval 95%)	1857 (1641 to 2101)	1887 (1672 to 2130)	1950 (1724 to 2207)

SNA GMT Ratios at Day 22 (Lot 104:Lot 105)

Statistical analysis description

Anti-CHIKV SNA GMT ratios between pairs of PXVX0317 (CHIKV VLP vaccine) Lots at Day 22. Group 1 (Lot 104) and Group 2 (Lot 105). Success criterion was pairwise GMT ratios (104:105, 105:106, 104:106) each with a two-sided 95% CI within [0.667; 1.5]. All 3 coprimary endpoints were required to be met for success, so no multiple comparisons were performed. GMT estimates and 95% CIs derived from an ANOVA model that includes site and product lot as fixed effects assuming normality of log titres.

Comparison groups

Group 1 - PXVX0317 Lot 104 v Group 2 - PXVX0317 Lot 105

Number of subjects included in analysis

986

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

GMT Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.14

SNA GMT Ratios at Day 22 (Lot 105:Lot 106)

Statistical analysis description

Anti-CHIKV SNA GMT ratios between pairs of PXVX0317 (CHIKV VLP vaccine) Lots at Day 22. Group 2 (Lot 105) and Group 3 (Lot 106). Success criterion was pairwise GMT ratios (104:105,105:106,104:106) each with a two-sided 95% CI within [0.667; 1.5]. All 3 coprimary endpoints were required to be met for success, so no multiple comparisons were performed. GMT estimates and 95% CIs derived from an ANOVA model that includes site and product lot as fixed effects assuming normality of log titres

Comparison groups

Group 2 - PXVX0317 Lot 105 v Group 3 - PXVX0317 Lot 106

Number of subjects included in analysis

992

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

GMT Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.12

SNA GMT Ratios at Day 22 (Lot 104:Lot 106)

Statistical analysis description

Anti-CHIKV SNA GMT ratios between pairs of PXVX0317 (CHIKV VLP vaccine) Lots at Day 22. Group 1 (Lot 104) and Group 3 (Lot 106). Success criterion was pairwise GMT ratios (104:105, 105:106, 104:106) each with a two-sided 95% CI within [0.667; 1.5]. All 3 coprimary endpoints were required to be met for success, so no multiple comparisons were performed. GMT estimates and 95% CIs derived from an ANOVA model that includes site and product lot as fixed effects assuming normality of log titres.

Comparison groups

Group 3 - PXVX0317 Lot 106 v Group 1 - PXVX0317 Lot 104

Number of subjects included in analysis

982

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

GMT Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.1

Secondary: Anti-CHIKV SNA seroresponse rates at Days 15

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End point title

Anti-CHIKV SNA seroresponse rates at Days 15 ^[11]

End point description

Anti-CHIKV SNA seroresponse rates for PXVX0317 and placebo, difference (PXVX0317 minus placebo), and associated 95% CIs at Day 15 for the IEP, all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

14 days post-vaccination

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	395	2434
Units: percentage of participants
number (confidence interval 95%)	0.8 (0.3 to 2.2)	96.8 (96.0 to 97.4)

Anti-CHIKV SNA seroresponse rates at Day 15

Statistical analysis description

Key secondary endpoints were tested hierarchically, such that each was only tested if all 3 coprimary endpoints and prior key secondary endpoints were met, so no multiple comparisons were performed. Seroresponse rate difference is (PXVX0317 minus placebo).

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2829

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[12]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

94.3

upper limit

96.8

Notes
[12] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Anti-CHIKV SNA seroresponse rates at Day 183

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End point title

Anti-CHIKV SNA seroresponse rates at Day 183 ^[13]

End point description

Anti-CHIKV SNA seroresponse rates for PXVX0317 (CHIKV VLP vaccine) and placebo, difference (PXVX0317 minus placebo), and associated 95% CIs at Day 183 for the IEP, all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

182 days post-vaccination

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	401	2301
Units: percentage of participants
number (confidence interval 95%)	1.5 (0.7 to 3.2)	85.5 (84.0 to 86.9)

Anti-CHIKV SNA seroresponse rates at Day 183

Statistical analysis description

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2702

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[14]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

81.7

upper limit

85.6

Notes
[14] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Anti-CHIKV SNA seroresponse rates at Day 8

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End point title

Anti-CHIKV SNA seroresponse rates at Day 8 ^[15]

End point description

Anti-CHIKV SNA seroresponse rates for PXVX0317 and placebo, difference (PXVX0317 minus placebo), and associated 95% CIs at Day 8 for the IEP, all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

7 days post-vaccination

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	419	2510
Units: percentage of participants
number (confidence interval 95%)	0.5 (0.1 to 1.7)	46.6 (44.6 to 48.5)

Anti-CHIKV SNA seroresponse rates at Day 8

Statistical analysis description

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2929

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[16]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

46.1

Confidence interval

level

95%

sides

2-sided

lower limit

43.8

upper limit

48.1

Notes
[16] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 8

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End point title

Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 8 ^[17]

End point description

Anti-CHIKV SNA GMTs with associated 95% CIs at Day 8 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

7 days post-vaccination

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	419	2510
Units: Titre
geometric mean (confidence interval 95%)	7 (6 to 8)	93 (87 to 100)

Anti-CHIKV SNA Geometric Mean Titres at Day 8

Statistical analysis description

Ratio of GMTs is (PXVX0317:placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2929

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[18]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[18] - ANOVA model includes site and treatment group as fixed effects, assuming normality of log titres. P-value tests equivalence of group GMTs on log scale.

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 15

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End point title

Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 15 ^[19]

End point description

Anti-CHIKV SNA GMTs with associated 95% CIs at Day 15 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

14 days post-vaccination

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	395	2434
Units: Titre
geometric mean (confidence interval 95%)	8 (7 to 9)	1096 (1029 to 1167)

Anti-CHIKV SNA Geometric Mean Titres at Day 15

Statistical analysis description

Ratio of GMTs is (PXVX0317:placebo).

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2829

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[20]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

144

Confidence interval

level

95%

sides

2-sided

lower limit

128

upper limit

162

Notes
[20] - ANOVA model includes site and treatment group as fixed effects, assuming normality of log titres. P-value tests equivalence of group GMTs on log scale.

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 183

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End point title

Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 183 ^[21]

End point description

Anti-CHIKV SNA GMTs with associated 95% CIs at Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

182 days post-vaccination

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	401	2301
Units: Titre
geometric mean (confidence interval 95%)	8 (7 to 9)	338 (318 to 358)

Anti-CHIKV SNA Geometric Mean Titres at Day 183

Statistical analysis description

Ratio of GMTs is (PXVX0317:placebo).

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2702

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[22]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[22] - ANOVA model includes site and treatment group as fixed effects, assuming normality of log titres. P-value tests equivalence of group GMTs on log scale.

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 8

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End point title

Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 8 ^[23]

End point description

Geometric mean fold increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 8 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at both Day 1 and the indicated visit.

End point type

Secondary

End point timeframe

7 days post-vaccination

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	419	2510
Units: Fold increase in geometric mean titre
number (confidence interval 95%)	1.0 (0.9 to 1.1)	12.5 (11.6 to 13.3)

GMFI in SNA Titres from Day 1 to Day 8

Statistical analysis description

Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titres from Day 1 to Day 8

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2929

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[24]

Method

t-test, 2-sided

Confidence interval

Notes
[24] - GMFI estimates and 95% CIs are based on t-statistics assuming a normal distribution of the log fold increase in titre. P-value tests equality of log fold increase in titre between groups.

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 15

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End point title

Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 15 ^[25]

End point description

Geometric mean fold increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 15 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at both Day 1 and the indicated visit.

End point type

Secondary

End point timeframe

14 days post-vaccination

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	395	2434
Units: Fold increase in geometric mean titre
number (confidence interval 95%)	1.0 (0.9 to 1.1)	146.1 (137.2 to 155.6)

GMFI in SNA Titres from Day 1 to Day 15

Statistical analysis description

Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titres from Day 1 to Day 15

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2829

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[26]

Method

t-test, 2-sided

Confidence interval

Notes
[26] - GMFI estimates and 95% CIs are based on t-statistics assuming a normal distribution of the log fold increase in titre. P-value tests equality of log fold increase in titre between groups.

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 22

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End point title

Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 22 ^[27]

End point description

Geometric mean fold increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 22 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at both Day 1 and the indicated visit.

End point type

Secondary

End point timeframe

21 days post-vaccination

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	424	2559
Units: Fold increase in geometric mean titre
number (confidence interval 95%)	1.1 (0.9 to 1.2)	215.7 (203.0 to 229.3)

GMFI in SNA Titres from Day 1 to Day 22

Statistical analysis description

Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titres from Day 1 to Day 22

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2983

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[28]

Method

t-test, 2-sided

Confidence interval

Notes
[28] - GMFI estimates and 95% CIs are based on t-statistics assuming a normal distribution of the log fold increase in titre. P-value tests equality of log fold increase in titre between groups.

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 183

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End point title

Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 183 ^[29]

End point description

Geometric mean fold increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 183 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at both Day 1 and the indicated visit.

End point type

Secondary

End point timeframe

182 days post-vaccination

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	401	2301
Units: Fold increase in geometric mean titre
number (confidence interval 95%)	1.1 (1.0 to 1.2)	45.0 (42.4 to 47.8)

GMFI in SNA Titres from Day 1 to Day 183

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2702

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[30]

Method

t-test, 2-sided

Confidence interval

Notes
[30] - GMFI estimates and 95% CIs are based on t-statistics assuming a normal distribution of the log fold increase in titre. P-value tests equality of log fold increase in titre between groups.

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 8

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End point title

Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 8 ^[31]

End point description

Number and percentage of participants with anti-CHIKV SNA titres ≥15 at Day 8 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

7 days post-vaccination

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	419	2510
Units: Percentage of participants
number (confidence interval 95%)	1.2 (0.5 to 2.8)	91.9 (90.7 to 92.9)

SNA Titres ≥15 at Day 8

Statistical analysis description

Seroresponse rate difference is (PXVX0317 minus placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2929

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[32]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

90.7

Confidence interval

level

95%

sides

2-sided

lower limit

88.7

upper limit

91.9

Notes
[32] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 15

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End point title

Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 15 ^[33]

End point description

Number and percentage of participants with anti-CHIKV SNA titres ≥15 at Day 15 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

14 days post-vaccination

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	395	2434
Units: Percentage of participants
number (confidence interval 95%)	0.8 (0.3 to 2.2)	99.5 (99.1 to 99.7)

SNA Titres ≥15 at Day 15

Statistical analysis description

Seroresponse rate difference is (PXVX0317 minus placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2829

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[34]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

98.7

Confidence interval

level

95%

sides

2-sided

lower limit

97.2

upper limit

99.3

Notes
[34] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 22

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End point title

Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 22 ^[35]

End point description

Number and percentage of participants with anti-CHIKV SNA titres ≥15 at Day 22 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

21 days post-vaccination

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	424	2559
Units: Percentage of participants
number (confidence interval 95%)	1.7 (0.8 to 3.4)	99.2 (98.8 to 99.5)

SNA Titres ≥15 at Day 22

Statistical analysis description

Seroresponse rate difference is (PXVX0317 minus placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2983

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[36]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

97.6

Confidence interval

level

95%

sides

2-sided

lower limit

95.8

upper limit

98.5

Notes
[36] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 183

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End point title

Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 183 ^[37]

End point description

Number and percentage of participants with anti-CHIKV SNA titres ≥15 at Day 183 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at the indicated visit.

End point type

Secondary

End point timeframe

182 days post-vaccination

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	401	2301
Units: Percentage of participants
number (confidence interval 95%)	2.2 (1.2 to 4.2)	99.0 (98.6 to 99.4)

SNA Titres ≥15 at Day 183

Statistical analysis description

Seroresponse rate difference is (PXVX0317 minus placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2702

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[38]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

96.8

Confidence interval

level

95%

sides

2-sided

lower limit

94.8

upper limit

97.9

Notes
[38] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 8

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End point title

Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 8 ^[39]

End point description

Number and percentage of participants with ≥4-fold rise over baseline at Day 8 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at Day 1 and at the indicated visit.

End point type

Secondary

End point timeframe

7 days post-vaccination

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	419	2510
Units: Percentage of participants
number (confidence interval 95%)	0.7 (0.2 to 2.1)	65.5 (63.6 to 67.3)

≥4-fold rise over Baseline at Day 8

Statistical analysis description

Seroresponse rate difference is (PXVX0317 minus placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2929

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[40]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

64.8

Confidence interval

level

95%

sides

2-sided

lower limit

62.5

upper limit

66.7

Notes
[40] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 15

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End point title

Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 15 ^[41]

End point description

Number and percentage of participants with ≥4-fold rise over baseline at Day 15 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at Day 1 and at the indicated visit.

End point type

Secondary

End point timeframe

14 days post-vaccination

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	395	2434
Units: Percentage of participants
number (confidence interval 95%)	0.8 (0.3 to 2.2)	98.6 (98.0 to 99.0)

≥4-fold rise over Baseline at Day 15

Statistical analysis description

Seroresponse rate difference is (PXVX0317 minus placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2829

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[42]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

97.8

Confidence interval

level

95%

sides

2-sided

lower limit

96.3

upper limit

98.4

Notes
[42] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 22

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End point title

Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 22 ^[43]

End point description

Number and percentage of participants with ≥4-fold rise over baseline at Day 22 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at Day 1 and at the indicated visit.

End point type

Secondary

End point timeframe

21 days post-vaccination

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	424	2559
Units: Percentage of participants
number (confidence interval 95%)	1.4 (0.7 to 3.1)	98.6 (98.1 to 99.0)

≥4-fold rise over Baseline at Day 22

Statistical analysis description

Seroresponse rate difference is (PXVX0317 minus placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2983

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

97.2

Confidence interval

level

95%

sides

2-sided

lower limit

95.5

upper limit

98.1

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 183

Top of page

End point title

Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 183 ^[44]

End point description

Number and percentage of participants with ≥4-fold rise over baseline at Day 183 for the IEP for all age strata combined. Analysis population was the Immunogenicity evaluable population (IEP): all randomised and vaccinated participants who provided an evaluable Day 22 anti-CHIKV human SNA sample within the analysis window, had no measurable anti-CHIKV human SNA assay titre at Day 1 (i.e., seronegative at baseline; participants missing a Day 1 titre were excluded from IEP), and had no important protocol deviation deemed exclusionary or other reason to be excluded as defined prior to unblinding. Number of subjects analysed is number of participants with a sample result available at Day 1 and at the indicated visit.

End point type

Secondary

End point timeframe

182 days post-vaccination

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Study had 4 arms - Group 1, Group 2, Group 3, and Group 4. The additional arm, 'pooled PXVX0317', was created for reporting purposes on EudraCT. Endpoint is reporting for Group 4 (Placebo) and the 'Pooled PXVX0317' Group (which is inclusive of CHIKV-VLP vaccinated participants in Group 1, Group 2, and Group 3). Therefore, data is being reported for participants from all arms of the study.

End point values	Group 4 - Placebo	Pooled PXVX0317
Number of subjects analysed	401	2301
Units: Percentage of participants
number (confidence interval 95%)	1.5 (0.7 to 3.2)	92.9 (91.8 to 93.9)

≥4-fold rise over Baseline at Day 183

Statistical analysis description

Seroresponse rate difference is (PXVX0317 minus placebo)

Comparison groups

Group 4 - Placebo v Pooled PXVX0317

Number of subjects included in analysis

2702

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[45]

Method

Chi-squared

Parameter type

Mean difference (final values)

Point estimate

91.4

Confidence interval

level

95%

sides

2-sided

lower limit

89.4

upper limit

92.7

Notes
[45] - p-value is from a two-sided chi-square test of equality of seroresponse percentages between groups.

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events were collected from Day 1 through to the Day 183 end of study visit.

Adverse event reporting additional description

A solicited AE is a protocol-specified AE which the investigator (or designee) proactively asks the participants during a protocol-specified time period. (Systematic Assessment) An unsolicited AE is an AE that is spontaneously reported by the participant or discovered by investigator (Non-systematic Assessment).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Group 4 - Placebo

Reporting group description

Biological/Vaccine: Placebo Placebo is comprised of formulation buffer

Reporting group title

Pooled PXVX0317

Reporting group description

All participants that received CHIKV VLP vaccine. Includes all participants in Group 1 (PXVX0317 Lot 104) + Group 2 (PXVX0317 Lot 105) + Group 3 (PXVX0317 Lot 106).

Serious adverse events	Group 4 - Placebo	Pooled PXVX0317
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 464 (0.22%)	23 / 2790 (0.82%)
number of deaths (all causes)	0	1
number of deaths resulting from adverse events	0	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Bipolar disorder
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Depression
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Craniocerebral injury
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Femoral neck fracture
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gun shot wound
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Road traffic accident
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Skin laceration
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Arnold-Chiari malformation
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Encephalocele
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Basal ganglia infarction
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neuropathy peripheral
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Retinal detachment
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Vomiting
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary retention
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Appendicitis
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 464 (0.22%)	0 / 2790 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tubo-ovarian abscess
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	1 / 2790 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic ketoacidosis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 464 (0.00%)	2 / 2790 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Group 4 - Placebo	Pooled PXVX0317
Total subjects affected by non serious adverse events
subjects affected / exposed	127 / 464 (27.37%)	1065 / 2790 (38.17%)
Nervous system disorders
Headache
subjects affected / exposed	78 / 464 (16.81%)	508 / 2790 (18.21%)
occurrences all number	78	523
General disorders and administration site conditions
Chills
subjects affected / exposed	15 / 464 (3.23%)	239 / 2790 (8.57%)
occurrences all number	15	240
Fatigue
subjects affected / exposed	79 / 464 (17.03%)	557 / 2790 (19.96%)
occurrences all number	79	564
Injection site pain
subjects affected / exposed	49 / 464 (10.56%)	657 / 2790 (23.55%)
occurrences all number	49	661
Gastrointestinal disorders
Nausea
subjects affected / exposed	31 / 464 (6.68%)	212 / 2790 (7.60%)
occurrences all number	31	221
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	34 / 464 (7.33%)	225 / 2790 (8.06%)
occurrences all number	36	230
Myalgia
subjects affected / exposed	45 / 464 (9.70%)	488 / 2790 (17.49%)
occurrences all number	46	492

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

06 Jul 2021

The major edit in protocol version 2.0 added the Day 15 visit for a more robust immunogenicity assessment. Hierarchical testing in the statistical section was added to control type I error.

10 Nov 2021

Minor edits in protocol version 3.0 included updates to the key study contact information related to the medical monitoring team, inclusion criteria, and labeling of the IP.

10 Feb 2022

Minor edits in protocol version 4.0 updated exclusion criterion 11, added a purpose statement, added HCV RNA testing if HCV antibody was positive, and clarified the definition of medically attended visits.

20 Mar 2023

Protocol version 5.0 updated the study objectives and endpoints per regulatory (US FDA and EMA) discussions.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3 Safety, Immunogenicity, and Lot-Consistency Trial of the VLP-Based Chikungunya Vaccine PXVX0317 in Healthy Adults and Adolescents

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Incidence of solicited Adverse Events (AE)

Primary: Incidence of solicited Adverse Events (AE)

Primary: Incidence of unsolicited AEs

Primary: Incidence of unsolicited AEs

Primary: Incidence of Adverse Events of Special Interest (AESI)

Primary: Incidence of Adverse Events of Special Interest (AESI)

Primary: Incidence of Medically Attended Adverse Event (MAAE)

Primary: Incidence of Medically Attended Adverse Event (MAAE)

Primary: Incidence of Serious Adverse Event (SAE)

Primary: Incidence of Serious Adverse Event (SAE)

Primary: Anti-CHIKV serum neutralising antibody (SNA) seroresponse rates at Day 22

Primary: Anti-CHIKV serum neutralising antibody (SNA) seroresponse rates at Day 22

Primary: Anti-CHIKV SNA geometric mean titres (GMT) at Day 22

Primary: Anti-CHIKV SNA geometric mean titres (GMT) at Day 22

Primary: Anti-CHIKV SNA GMT ratios between pairs of PXVX0317 (CHIKV VLP vaccine) lots at Day 22

Primary: Anti-CHIKV SNA GMT ratios between pairs of PXVX0317 (CHIKV VLP vaccine) lots at Day 22

Secondary: Anti-CHIKV SNA seroresponse rates at Days 15

Secondary: Anti-CHIKV SNA seroresponse rates at Days 15

Secondary: Anti-CHIKV SNA seroresponse rates at Day 183

Secondary: Anti-CHIKV SNA seroresponse rates at Day 183

Secondary: Anti-CHIKV SNA seroresponse rates at Day 8

Secondary: Anti-CHIKV SNA seroresponse rates at Day 8

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 8

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 8

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 15

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 15

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 183

Secondary: Anti-CHIKV SNA Geometric Mean Titres (GMTs) at Day 183

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 8

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 8

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 15

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 15

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 22

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 22

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 183

Secondary: Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titres from Day 1 to Day 183

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 8

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 8

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 15

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 15

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 22

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 22

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 183

Secondary: Number and Percentage of Participants with Anti-CHIKV SNA Titre ≥15 at Day 183

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 8

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 8

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 15

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 15

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 22

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 22

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 183

Secondary: Number and Percentage of Participants with ≥4-fold Rise over Baseline at Day 183

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 3 Safety, Immunogenicity, and Lot-Consistency Trial of the VLP-Based Chikungunya Vaccine PXVX0317 in Healthy Adults and Adolescents