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Clinical Trial Results:
Double blinded, randomized, Priorix®- and placebo-controlled, trial to evaluate the optimal dose of MV-CHIK vaccine (against Chikungunya virus) in regard to immunogenicity, safety and tolerability in healthy volunteers

Summary
EudraCT number	2015-004037-26
Trial protocol	DE AT
Global end of trial date	16 Apr 2018

Results information
Results version number	v2(current)
This version publication date	10 Nov 2021
First version publication date	09 Feb 2020
Other versions	v1
Version creation reason

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

MV-CHIK-202

ISRCTN number

US NCT number

NCT02861586

WHO universal trial number (UTN)

Sponsor organisation name

Themis Bioscience GmbH

Sponsor organisation address

Muthgasse 11/2, Vienna, Austria, 1190

Public contact

Andrea Pfeiffer, MSc Clinica Project Officer, Themis Bioscience GmbH, +43 6765102835, andrea.pfeiffer@themisbio.com

Scientific contact

Dr. Katrin Ramsauer Chief Scientific Officer, Themis Bioscience GmbH, +43 676843496418, katrin.ramsauer@themisbio.com

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

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?

Analysis stage

Final

Date of interim/final analysis

16 Apr 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

01 Sep 2017

Global end of trial reached?

Yes

Global end of trial date

16 Apr 2018

Was the trial ended prematurely?

Main objective of the trial

To investigate the immunogenicity and safety of MV-CHIK 28 days after primary immunization regime, comprising one or two vaccinations.

Protection of trial subjects

Subjects’ safety was an essential concern in this clinical study MV-CHIK-202 and was addressed in the clinical study protocol: -Physical examination: During each study visit subjects underwent a symptom-directed physical examination and the assessment of vital signs like systolic and diastolic blood pressure, pulse and body temperature, allowed to detect and record adverse conditions. -Post vaccination reactogenicity assessment: All subjects were observed for 1 hour after each vaccination in order to investigate local and systemic tolerability and to ensure the subjects wellbeing before discharge. -AEs: For general safety reasons, all subjects that at least received one vaccination were followed up for at least 28 days after the last vaccination. -Body temperature: All subjects received a thermometer and were asked to note their daily body temperature in a diary for 7 days after each vaccination to perceive side effects. -Subject diary: Solicited AEs were recorded by the subjects by checking the presence of listed symptoms in a subject’s diary. The diary provided also space for noting unsolicited AEs and concomitant medication. This enabled the subjects to better remember AEs and the investigator to gather and assess AEs in more detail. -Laboratory parameters: were regularly measured to reveal clinically relevant lab values on hematology, blood chemistry, coagulation parameters and urinalysis. All lab results were evaluated carefully by the investigator to identify adverse conditions. -Safety stopping rules: An independent DSMB was installed to review safety information, and if necessary, to determine whether study or individual subject stopping rules have been met. -Data Safety Monitoring Board (DSMB): In close cooperation with the DSMB and the investigators the protection of study participants was assured.

Background therapy

n.a.

Evidence for comparator

Priorix® (Glaxo Smith Kline GSK) a measles, mumps, rubella vaccine was used as a control-vaccine because the contained attenuated Schwarz measles virus strain is the same strain, used as backbone in MV-CHIK.

Actual start date of recruitment

17 Aug 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 168

Country: Number of subjects enrolled

Germany: 95

Worldwide total number of subjects

263

EEA total number of subjects

263

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)

Adults (18-64 years)

263

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

First subject in, Austria: 17-Aug-2016 Last subject out, Austria: 11-Jan-2018 First subject in, Germany: 04-May-2017 Last subject out, Germany: 16-Apr-2018

Screening details

To confirm the health status of volunteers the following data and parameters were assessed during screening: Medical/vacination history, physical examination, hematology, coagulation parameters, HIV, hepatitis B/C, urinalysis

Period 1 title

overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Assessor, Subject, Investigator, Monitor

Blinding implementation details

This study was conducted in a double-blind manner in regard to assignment to Treatment Groups A, B, C or D. An assignment to the measles booster groups M1 and M2 was apparent to both subject and study personnel, but the vaccination sequence was kept double-blind (allocation to M1 or to M2 was unknown). Vaccine was prepared by authorized unblinded personnel otherwise not involved in the conduct of the study. Ready prepared syringes were blinded.

Are arms mutually exclusive

Yes

Treatment Group A; MV-CHIK Low

Arm description

Participants received i.m. vaccinations with MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Arm type

Experimental

Investigational medicinal product name

Placebo NaCl 0.9%

Investigational medicinal product code

Placebo

Other name

Physiological saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Treatment group A received i.m. vaccinations with 0.3 ml MV-CHIK low dose on study day 0 and 28, and 0.3 ml placebo on day 196.

Investigational medicinal product name

MV-CHIK low dose 5x10E4 (± 0.5 log) TCID50/dose

Investigational medicinal product code

MV-CHIK

Other name

Chikungunya vaccine

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Treatment group A received i.m. vaccinations with 0.3 ml MV-CHIK low dose on study day 0 and 28, and 0.3 ml placebo on day 196.

Treatment Group B; MV-CHIK Low

Arm description

Participants received i.m. vaccinations with placebo on study day 0; MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on day 28 and MV-CHIK boosting dose on day 196.

Arm type

Experimental

Investigational medicinal product name

MV-CHIK low dose 5x10E4 (± 0.5 log) TCID50/ dose

Investigational medicinal product code

MV-CHIK

Other name

Chikungunya vaccine

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Group B subjects received i.m. vaccinations with 0.3 ml placebo on study day 0, and 0.3 ml MV-CHIK low dose on day 28 and on day 196.

Investigational medicinal product name

Placebo NaCl 0.9%

Investigational medicinal product code

Placebo

Other name

physiological saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Group B subjects received i.m. vaccinations with 0.3 ml placebo on study day 0, and 0.3 ml MV-CHIK low dose on day 28 and on day 196.

Treatment Group C; MV-CHIK High

Arm description

Participants received i.m. vaccinations with MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Arm type

Experimental

Investigational medicinal product name

Placebo NaCl 0.9%

Investigational medicinal product code

Placebo

Other name

Physiological saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Group C received i.m. vaccinations with 0.3 ml MV-CHIK high dose on study day 0 and 28, and 0.3 ml placebo on day 196.

Investigational medicinal product name

MV-CHIK high dose 5x10E5 (± 0.5 log) TCID50/ dose

Investigational medicinal product code

MV-CHIK

Other name

Chikungunya vaccine

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Intranasal use

Dosage and administration details

Group C received i.m. vaccinations with 0.3 ml MV-CHIK high dose on study day 0 and 28, and 0.3 ml placebo on day 196.

Treatment Group D; MV-CHIK High

Arm description

Participants received i.m. vaccinations with placebo on study day 0, MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 28 and MV-CHIK boosting dose on day 196.

Arm type

Experimental

Investigational medicinal product name

Placebo NaCl 0.9%

Investigational medicinal product code

Placebo

Other name

Physiological saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Group D received i.m. vaccinations with 0.3 ml placebo on study day 0, and 0.3 ml MV-CHIK high dose on study day 28 and on day 196.

Investigational medicinal product name

MV-CHIK high dose 5x10E5 (± 0.5 log) TCID50/ dose

Investigational medicinal product code

MV-CHIK

Other name

Chikungunya vaccine

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Intranasal use

Dosage and administration details

Group D received i.m. vaccinations with 0.3 ml placebo on study day 0, and 0.3 ml MV-CHIK high dose on study day 28 and on day 196.

Measles Booster Group 1

Arm description

Participants received i.m. vaccinations with Priorix® on study day -28, MV-CHIK on day 0 and 28, and placebo on day 168 and 196.

Arm type

Experimental

Investigational medicinal product name

Priorix® measles, mumps rubella vaccine

Investigational medicinal product code

Priorix® controll vaccine

Other name

comperator

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects of group M1 received the control vaccine (Priorix®) 28 days prior to two MV-CHIK vaccinations on day 0 and 28, followed by two placebo injections on day 168 and 196.

Measles Booster Group 2

Arm description

Participants received i.m. vaccinations with Priorix® on study day -28, placebo on day 0 and 28, and MV-CHIK on day 168 and 196.

Arm type

Experimental

Investigational medicinal product name

Priorix® measles, mumps, rubella vaccine

Investigational medicinal product code

Priorix®controll vaccine

Other name

comperator

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Group M2 received the control vaccine (Priorix®) 28 days prior to two placebo injections on day 0 and 28, followed by two MV-CHIK vaccinations on day 168 and 196.

Treatment Group A/C; Priorix®

Arm description

Participants received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.

Arm type

Active comparator

Investigational medicinal product name

Priorix® measles, mumps, rubella vaccine

Investigational medicinal product code

Priorix® control vaccine

Other name

comperator

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Control Group CV1, A/C received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.

Investigational medicinal product name

Placebo NaCl 0.9%

Investigational medicinal product code

Placebo

Other name

Physiological saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Control Group CV1, A/C received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.

Treatment Group B/D; Priorix®

Arm description

Participants received i.m. vaccinations with placebo on study day 0, Priorix® on day 28 and one boosting dose with Priorix® on day 196.

Arm type

Active comparator

Investigational medicinal product name

Priorix® measles, mumps, rubella vaccine

Investigational medicinal product code

Priorix® control vaccine

Other name

comperator

Pharmaceutical forms

Powder and solvent for solution for injection/skin-prick test

Routes of administration

Intramuscular use

Dosage and administration details

Control Group CV2, B/D received i.m. vaccinations with placebo on study day 0, and Priorix® on day 28 and day 196.

Investigational medicinal product name

Placebo NaCl 0.9%

Investigational medicinal product code

Placebo

Other name

Physiological saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Control Group CV2, B/D received i.m. vaccinations with placebo on study day 0, and Priorix® on day 28 and day 196.

Number of subjects in period 1	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Started	51	47	47	50	18	16	18	16
Completed	47	46	47	45	17	16	15	16
Not completed	4	1	0	5	1	0	3	0
Consent withdrawn by subject	1	-	-	1	1	-	2	-
Adverse event, non-fatal	-	-	-	1	-	-	-	-
Lost to follow-up	3	1	-	3	-	-	1	-

Baseline characteristics

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Reporting group title

Treatment Group A; MV-CHIK Low

Reporting group description

Participants received i.m. vaccinations with MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Reporting group title

Treatment Group B; MV-CHIK Low

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0; MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on day 28 and MV-CHIK boosting dose on day 196.

Reporting group title

Treatment Group C; MV-CHIK High

Reporting group description

Participants received i.m. vaccinations with MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Reporting group title

Treatment Group D; MV-CHIK High

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0, MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 28 and MV-CHIK boosting dose on day 196.

Reporting group title

Measles Booster Group 1

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day -28, MV-CHIK on day 0 and 28, and placebo on day 168 and 196.

Reporting group title

Measles Booster Group 2

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day -28, placebo on day 0 and 28, and MV-CHIK on day 168 and 196.

Reporting group title

Treatment Group A/C; Priorix®

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.

Reporting group title

Treatment Group B/D; Priorix®

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0, Priorix® on day 28 and one boosting dose with Priorix® on day 196.

Reporting group values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®	Total
Number of subjects	51	47	47	50	18	16	18	16	263
Age categorical
Units:
Age continuous
Units: years
arithmetic mean (standard deviation)	31.4 ± 10.13	32.7 ± 10.53	35.1 ± 12.32	31.2 ± 9.93	31.1 ± 10.41	32.6 ± 10.28	32.2 ± 10.01	33.6 ± 11.56	-
Gender categorical
Units: Subjects
Female	27	29	24	27	11	5	10	7	140
Male	24	18	23	23	7	11	8	9	123

End points

Top of page

Reporting group title

Treatment Group A; MV-CHIK Low

Reporting group description

Participants received i.m. vaccinations with MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Reporting group title

Treatment Group B; MV-CHIK Low

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0; MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on day 28 and MV-CHIK boosting dose on day 196.

Reporting group title

Treatment Group C; MV-CHIK High

Reporting group description

Participants received i.m. vaccinations with MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Reporting group title

Treatment Group D; MV-CHIK High

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0, MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 28 and MV-CHIK boosting dose on day 196.

Reporting group title

Measles Booster Group 1

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day -28, MV-CHIK on day 0 and 28, and placebo on day 168 and 196.

Reporting group title

Measles Booster Group 2

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day -28, placebo on day 0 and 28, and MV-CHIK on day 168 and 196.

Reporting group title

Treatment Group A/C; Priorix®

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.

Reporting group title

Treatment Group B/D; Priorix®

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0, Priorix® on day 28 and one boosting dose with Priorix® on day 196.

Subject analysis set title

Baseline measles titer percentile 0 to 25%

Subject analysis set type

Per protocol

Subject analysis set description

Participants in Treatment Groups A, B, C, and D categorized according to baseline measles titer value.

Subject analysis set title

Baseline measles titer percentile 25 to 50%

Subject analysis set type

Per protocol

Subject analysis set description

Participants in Treatment Groups A, B, C, and D categorized according to baseline measles titer value.

Subject analysis set title

Baseline measles titer percentile 50 to 75%

Subject analysis set type

Per protocol

Subject analysis set description

Participants in Treatment Groups A, B, C, and D categorized according to baseline measles titer value.

Subject analysis set title

Baseline measles titer percentile 75 to 100%

Subject analysis set type

Per protocol

Subject analysis set description

Participants in Treatment Groups A, B, C, and D categorized according to baseline measles titer value.

Primary: Functional Anti-chikungunya Antibody Titers on Day 56 (28 Days Post Immunisation) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

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End point title

Functional Anti-chikungunya Antibody Titers on Day 56 (28 Days Post Immunisation) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

End point description

Immunogenicity on day 56 confirmed by the presence of functional anti-chikungunya antibodies as determined by the plaque reduction neutralization test (PRNT50). This means immunogenicity 28 days after primary immunization regime, comprising one or two vaccinations. The Per-Protocol (PP) population was defined as the mITT population minus subjects with at least one major protocol deviation.

End point type

Primary

End point timeframe

Study day 56 (28 days after one or two vaccinations depending on treatment group).

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	49	44	47	44	16	15	16	16
Units: Titer
geometric mean (standard deviation)	50.2 ± 127.69	12.9 ± 100.47	174.8 ± 436.11	33.6 ± 59.38	80.0 ± 233.80	5.0 ± 0.00	5.0 ± 0.00	5.0 ± 0.00

Treatment Group A vs Treatment Group B

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group B; MV-CHIK Low v Treatment Group A; MV-CHIK Low

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[1]

Method

ANOVA

Parameter type

Geometric mean ratio

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

7.7

Variability estimate

Standard deviation

Notes
[1] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group A vs Treatment Group C

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group A; MV-CHIK Low v Treatment Group C; MV-CHIK High

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[2]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.6

Notes
[2] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group A vs Treatment Group D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group A; MV-CHIK Low v Treatment Group D; MV-CHIK High

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.06334 ^[3]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

Notes
[3] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group A vs Measles Booster Group 1

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group A; MV-CHIK Low v Measles Booster Group 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8065 ^[4]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

1.6

Notes
[4] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group A vs Measles Booster Group 2

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group A; MV-CHIK Low v Measles Booster Group 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[5]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.8

upper limit

26.6

Notes
[5] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group A vs Treatment Group A/C

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group A; MV-CHIK Low v Treatment Group A/C; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[6]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.3

Notes
[6] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group A vs Treatment Group B/D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group A; MV-CHIK Low v Treatment Group B/D; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[7]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.3

Notes
[7] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group B vs Treatment Group C

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group B; MV-CHIK Low v Treatment Group C; MV-CHIK High

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[8]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.1

Notes
[8] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group B vs Treatment Group D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group B; MV-CHIK Low v Treatment Group D; MV-CHIK High

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0011 ^[9]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.8

Notes
[9] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group B vs Measles Booster Group 1

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group B; MV-CHIK Low v Measles Booster Group 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[10]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.4

Notes
[10] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group B vs Measles Booster Group 2

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group B; MV-CHIK Low v Measles Booster Group 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0718 ^[11]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

6.9

Notes
[11] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group B vs Treatment Group A/C

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group B; MV-CHIK Low v Treatment Group A/C; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0593 ^[12]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

Notes
[12] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group B vs Treatment Group B/D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group B; MV-CHIK Low v Treatment Group B/D; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0593 ^[13]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

Notes
[13] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group C vs Treatment Group D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group C; MV-CHIK High v Treatment Group D; MV-CHIK High

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[14]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

10.4

Notes
[14] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group C vs Measles Booster Group 1

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group C; MV-CHIK High v Measles Booster Group 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2005 ^[15]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

5.7

Notes
[15] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group C vs Measles Booster Group 2

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group C; MV-CHIK High v Measles Booster Group 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[16]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

13.1

upper limit

93.1

Notes
[16] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group C vs Treatment Group A/C

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group C; MV-CHIK High v Treatment Group A/C; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[17]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.1

Notes
[17] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group C vs Treatment Group B/D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group C; MV-CHIK High v Treatment Group B/D; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[18]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.1

Notes
[18] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group D vs Measles Booster Group 1

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group D; MV-CHIK High v Measles Booster Group 1

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1138 ^[19]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

1.1

Notes
[19] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group D vs Measles Booster Group 2

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group D; MV-CHIK High v Measles Booster Group 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.0001 ^[20]

Method

ANOVA

Parameter type

Geometric mean ratio

Point estimate

6.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

18.1

Notes
[20] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group D vs. Treatment Group A/C

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group D; MV-CHIK High v Treatment Group A/C; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.0001 ^[21]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.4

Notes
[21] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group D vs Treatment Group B/D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group D; MV-CHIK High v Treatment Group B/D; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.0001 ^[22]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.4

Notes
[22] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Measles Booster Group 1 vs Measles Booster Group 2

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Measles Booster Group 1 v Measles Booster Group 2

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.0001 ^[23]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.9

upper limit

52.4

Notes
[23] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Measles Booster Group 1 vs Treatment Group A/C

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Measles Booster Group 1 v Treatment Group A/C; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.0001 ^[24]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.2

Notes
[24] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05

Measles Booster Group 1 vs Treatment Group B/D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Measles Booster Group 1 v Treatment Group B/D; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.0001 ^[25]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.2

Notes
[25] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05

Measles Booster Group 2 vs Treatment Group A/C

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Measles Booster Group 2 v Treatment Group A/C; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 1 ^[26]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

3.3

Notes
[26] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Measles Booster Group 2 vs Treatment Group B/D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Measles Booster Group 2 v Treatment Group B/D; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 1 ^[27]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

3.3

Notes
[27] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Treatment Group A/C vs Treatment Group B/D

Statistical analysis description

Analysis of variance was conducted with treatment group as a fixed factor.

Comparison groups

Treatment Group A/C; Priorix® v Treatment Group B/D; Priorix®

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 1 ^[28]

Method

ANOVA

Parameter type

Geometric Mean Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

3.2

Notes
[28] - Pairwise comparisons were adjusted for multiple tests according to Tukey-Kramer. The threshold for significance was 0.05.

Secondary: Functional Anti-Chikungunya Antibody Titers on Days 0, 28, 196 and 224 (M1/M2 Groups Day 168) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

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End point title

Functional Anti-Chikungunya Antibody Titers on Days 0, 28, 196 and 224 (M1/M2 Groups Day 168) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

End point description

Evaluation of immunogenicity on days 0, 28, 196 and 224; additionally, for group M1 and M2 on day 168 as confirmed by the presence of functional anti-chikungunya antibodies as determined by the plaque reduction neutralization test (PRNT50). Please note that for some timepoints testing has not been done. "Not done" cannot be entered but only numerical values. "9999" serves as indicator of a test which was not performed. The Per-Protocol (PP) population was defined as the mITT population minus subjects with at least one major protocol deviation.

End point type

Secondary

End point timeframe

Baseline until study day 224

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	49	44	47	44	16	15	16	16
Units: Titer
geometric mean (standard deviation)
Day 0	5.1 ± 0.71	5.3 ± 3.16	5.0 ± 0.00	5.0 ± 0.00	5.0 ± 0.00	5.0 ± 0.00	5.0 ± 0.00	5.0 ± 0.00
Day 28	11.2 ± 63.40	5.5 ± 3.82	25.7 ± 52.22	5.1 ± 0.75	13.5 ± 40.52	5.0 ± 0.00	5.0 ± 0.00	5.0 ± 0.00
Day 168	9999 ± 9999	9999 ± 9999	9999 ± 9999	9999 ± 9999	28.9 ± 52.25	5.0 ± 0.00	9999 ± 9999	9999 ± 9999
Day 196	13.5 ± 33.46	6.4 ± 8.29	38.8 ± 70.59	16.5 ± 81.75	24.1 ± 106.25	11.5 ± 26.04	5.0 ± 0.00	5.0 ± 0.00
Day 224	14.6 ± 37.87	70.5 ± 174.57	41.8 ± 105.55	609.8 ± 949.70	18.3 ± 87.50	66.5 ± 172.62	5.0 ± 0.00	5.0 ± 0.00

No statistical analyses for this end point

Secondary: Measurement of Anti-measles Antibody Titer by Enzyme Linked Immunosorbent Assay

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End point title

Measurement of Anti-measles Antibody Titer by Enzyme Linked Immunosorbent Assay

End point description

Measurement of anti-measles antibody titers on day 0, 28, and 56; additionally for group M1 and M2 on day -28 as determined by enzyme linked immunosorbent assay (ELISA). Please note that for some timepoints testing has not been done. "Not done" cannot be entered but only numerical values. "9999" should serve as indicator of a test which was not performed. The Per-Protocol (PP) population was defined as the mITT population minus subjects with at least one major protocol deviation.

End point type

Secondary

End point timeframe

Baseline until study day 56

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	49	44	47	44	16	15	16	16
Units: Titer
geometric mean (standard deviation)
Day -28	9999 ± 9999	9999 ± 9999	9999 ± 9999	9999 ± 9999	542.6 ± 1118.52	304.5 ± 343.53	9999 ± 9999	9999 ± 9999
Day 0	456.2 ± 1398.54	398.1 ± 1267.55	495.0 ± 1181.36	401.8 ± 1073.54	785.6 ± 1149.47	645.9 ± 850.56	693.9 ± 1307.42	390.4 ± 1106.86
Day 28	1509.4 ± 1360.83	396.9 ± 1183.04	2343.9 ± 1357.29	492.1 ± 1227.24	1761.5 ± 1578.85	561.2 ± 385.36	1200.6 ± 1129.77	447.5 ± 1139.37
Day 56	1651.8 ± 1384.39	1255.0 ± 1279.28	2750.5 ± 1284.23	2435.2 ± 1461.78	1825.2 ± 1459.93	521.4 ± 455.37	1129.4 ± 1168.63	673.8 ± 917.52

No statistical analyses for this end point

Secondary: Number of Participants With Solicited Local and Systemic Adverse Events

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End point title

Number of Participants With Solicited Local and Systemic Adverse Events

End point description

Evaluation of solicited local and systemic adverse events as recorded in the subjects' diaries for 7 days after each vaccination. As per the protocol, adverse events were analyzed per treatment group but were not assessed with respect to individual vaccinations. All safety analyses were based on the Safety Population, which included all subjects who received at least one vaccination.

End point type

Secondary

End point timeframe

Solicited adverse events were recorded for 7 days after each vaccination

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	51	47	47	50	18	16	18	16
Units: Participants	35	32	37	41	13	10	14	10

No statistical analyses for this end point

Secondary: Number of participants who experienced treatment emergent adverse events

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End point title

Number of participants who experienced treatment emergent adverse events

End point description

Evaluation of all treatment emergent adverse events (TEAEs) occurred throughout the clinical study. Clinically relevant abnormal safety laboratory values were recorded as TEAEs. As per the protocol, adverse events were analyzed per treatment group but were not assessed with respect to individual vaccinations. All safety analyses were based on the Safety Population, which included all subjects who received at least one vaccination.

End point type

Secondary

End point timeframe

First vaccination until study day 224

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	51	47	47	50	18	16	18	16
Units: Participants
TEAEs	29	27	22	18	11	9	10	7
Serious TEAEs	1	2	0	1	0	0	1	1
Severe TEAEs	1	2	0	2	1	1	1	0
Related TEAEs	8	11	4	10	4	5	2	1
Medically Attended TEAEs	12	15	9	8	4	3	3	1
TEAEs where an action was taken	0	1	0	1	0	0	0	1
TEAEs of special interest	2	2	0	1	2	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Urine Until Day 196

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End point title

Number of Participants With Shedding of Live Recombinant Virus in Urine Until Day 196 ^[29]

End point description

Shedding was observed in a subset of subjects at one Austrian study site, by qualitative determination of live recombinant measles virus in urine by polymerase chain reaction (PCR). As subjects of the measles booster groups M1 and M2 received a measles vaccination prior to the modified MV-CHIK vaccine, these groups had to be excluded from measles shedding analysis.

End point type

Secondary

End point timeframe

Baseline until study day 196; assessed on days 0, 7, 10, 14, 28 and 196

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: No statistic calculations were planned or performed - not one case of sheeding was observed. Shedding analysis relies on PCR methods amplifying measles sequences. As M1 and M2 groups receive a measles vaccination and the study vaccination (modified measles virus), a potential positive result would not be indicative of the reason and therefore these groups were not tested for shedding.

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	8	4	8	5	4	2
Units: Participants
Visit 1/Day 0	0	0	0	0	0	0
Day 7	0	0	0	0	0	0
Day 10	0	0	0	0	0	0
Day 14	0	0	0	0	0	0
Visit 2/Day 28	0	0	0	0	0	0
Visit 5/Day 196	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Saliva Until Day 196

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End point title

Number of Participants With Shedding of Live Recombinant Virus in Saliva Until Day 196 ^[30]

End point description

Shedding was observed in a subset of subjects at one Austrian study site, by qualitative determination of live recombinant measles virus in saliva by polymerase chain reaction (PCR). As subjects of the measles booster groups M1 and M2 received a measles vaccination prior to the modified MV-CHIK vaccine, these groups had to be excluded from measles shedding analysis.

End point type

Secondary

End point timeframe

Baseline until study day 196; assessed on days 0, 7, 10, 14, 28 and 196

Notes
[30] - 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: No statistic calculations were planned or performed - not one case of sheeding was observed. Shedding analysis relies on PCR methods amplifying measles sequences. As M1 and M2 groups receive a measles vaccination and the study vaccination (modified measles virus), a potential positive result would not be indicative of the reason and therefore these groups were not tested for shedding.

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	8	4	8	5	4	2
Units: Participants
Visit 1/Day 0	0	0	0	0	0	0
Day 7	0	0	0	0	0	0
Day 10	0	0	0	0	0	0
Day 14	0	0	0	0	0	0
Visit 2/Day 28	0	0	0	0	0	0
Visit 5/Day 196	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Chikungunya Virus Specific T Cell Responses

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End point title

Chikungunya Virus Specific T Cell Responses

End point description

Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood to determine functional IL-2-producing T cells on day 0, 28, 56 and 224 in a subset of subjects. ELISpots were performed using peptides covering the CHIK proteins E1, E2 and C for re-stimulation, thereby producing three values per sample representing the number of spots per 1 x 10^6 PBMCs. If one or more of the three values was greater than 50, the sample was considered positive and the highest of the three values was used in the analysis. If all three values were below 50, the sample was considered negative and a value of 0.0 was used for analysis. Please note that for some timepoints testing has not been done. "Not done" cannot be entered but only numerical values. "9999" should serve as indicator of a test which was not performed. A subset of the mITT Population was analyzed for T-cell Response.

End point type

Secondary

End point timeframe

Baseline until study day 224

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	15	12	14	11	5	4	5	5
Units: Titer
arithmetic mean (standard deviation)
Visit 1/Day 0	0.0 ± 0.00	12.1 ± 40.10	0.0 ± 0.00	0.0 ± 0.00	0.0 ± 0.00	9999 ± 9999	0.0 ± 0.00	0.0 ± 0.00
Visit 2/Day 28	41.5 ± 128.71	9999 ± 9999	10.5 ± 39.29	9999 ± 9999	9999 ± 9999	9999 ± 9999	0.0 ± 0.00	9999 ± 9999
Visit 3/Day 56	46.5 ± 63.54	36.7 ± 68.44	53.4 ± 74.83	6.5 ± 21.41	47.0 ± 51.55	0.0 ± 0.00	0.0 ± 0.00	25.2 ± 56.35
Visit 6/Day 224	28.3 ± 48.92	71.8 ± 13.2	11.6 ± 23.06	30.1 ± 61.48	0.0 ± 0.00	0.0 ± 0.00	0.0 ± 0.00	13.2 ± 29.52

No statistical analyses for this end point

Secondary: Immunogenicity confirmed by the presence of humoral anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA)

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End point title

Immunogenicity confirmed by the presence of humoral anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA)

End point description

Evaluation of immunogenicity mediated by serum IgG antibodies against Chikungunya on days 0, 28, 196 and 224; additionally for group M1 and M2 on day 168, determined by enzyme linked immunosorbent assay (ELISA). Please note that for some timepoints testing has not been done. "Not done" cannot be entered but only numerical values. "9999" should serve as indicator of a test which was not performed. The Per-Protocol (PP) population was defined as the mITT population minus subjects with at least one major protocol Deviation.

End point type

Secondary

End point timeframe

Baseline until study day 224; assessed on days 0, 28, 168, 196 and 224

End point values	Treatment Group A; MV-CHIK Low	Treatment Group B; MV-CHIK Low	Treatment Group C; MV-CHIK High	Treatment Group D; MV-CHIK High	Measles Booster Group 1	Measles Booster Group 2	Treatment Group A/C; Priorix®	Treatment Group B/D; Priorix®
Number of subjects analysed	49	44	47	44	16	15	16	16
Units: Titer
geometric mean (standard deviation)
Visit 1/Day 0	2.1 ± 1.94	2.3 ± 1.68	2.3 ± 2.75	2.2 ± 1.53	2.4 ± 2.69	2.2 ± 2.25	3.6 ± 3.64	1.7 ± 1.05
Visit 2/Day 28	3.2 ± 6.57	2.2 ± 1.81	6.2 ± 4.65	2.5 ± 1.74	4.3 ± 9.48	2.0 ± 2.37	3.4 ± 3.13	2.0 ± 2.75
Visit 3/Day 56	13.6 ± 31.84	3.4 ± 6.26	74.4 ± 41.45	6.6 ± 18.68	28.0 ± 47.51	2.3 ± 2.10	3.4 ± 4.06	1.7 ± 1.63
Visit 4/Day 168	9999 ± 9999	9999 ± 9999	9999 ± 9999	9999 ± 9999	9.5 ± 29.82	1.8 ± 2.28	9999 ± 9999	9999 ± 9999
Visit 5/Day 196	5.6 ± 3.0	3.0 ± 3.11	15.2 ± 25.08	5.6 ± 21.33	8.9 ± 24.13	3.6 ± 5.48	3.3 ± 4.02	1.9 ± 2.06
Visit 6/Day 224	4.6 ± 9.46	25.4 ± 52.43	13.1 ± 24.24	130.8 ± 43.94	7.3 ± 28.56	20.4 ± 43.19	3.1 ± 4.66	1.7 ± 1.82

No statistical analyses for this end point

Secondary: Functional anti-chikungunya antibody titers on day 56 (28 days post immunization) by baseline measles titer

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End point title

Functional anti-chikungunya antibody titers on day 56 (28 days post immunization) by baseline measles titer

End point description

To determine the potential impact of pre-existing antibodies against measles on MV-CHIK immunogenicity, participants from treatment Groups A to D were divided into quartiles according to serum IgG concentrations against measles virus on Day 0. Functional anti-chikungunya antibodies as determined by PRNT50 were compared between groups. The Per-Protocol (PP) population was defined as the mITT population minus subjects with at least one major protocol Deviation.

End point type

Secondary

End point timeframe

Study day 56 (28 days after one or two vaccinations depending on treatment group)

End point values	Baseline measles titer percentile 0 to 25%	Baseline measles titer percentile 25 to 50%	Baseline measles titer percentile 50 to 75%	Baseline measles titer percentile 75 to 100%
Number of subjects analysed	45	48	45	46
Units: Titer
geometric mean (standard deviation)	155.1 ± 532.68	177.0 ± 897.74	117.6 ± 346.86	100.8 ± 535.78

0 to 25% vs. 25 to 50%

Statistical analysis description

Analysis of variance was performed with baseline measles titer group as a fixed factor.

Comparison groups

Baseline measles titer percentile 25 to 50% v Baseline measles titer percentile 0 to 25%

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9775

Method

ANOVA

Parameter type

Geometric mean ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

0 to 25% vs 50 to 75%

Statistical analysis description

Analysis of variance was performed with baseline measles titer group as a fixed factor.

Comparison groups

Baseline measles titer percentile 0 to 25% v Baseline measles titer percentile 50 to 75%

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8366

Method

ANOVA

Parameter type

Geometric mean ratio

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

3.1

0 to 25% vs 75 to 100%

Statistical analysis description

Analysis of variance was performed with baseline measles titer group as a fixed factor.

Comparison groups

Baseline measles titer percentile 0 to 25% v Baseline measles titer percentile 75 to 100%

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5625

Method

ANOVA

Parameter type

Geometric mean ratio

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

3.6

25 to 50% vs 50 to 75%

Statistical analysis description

Analysis of variance was performed with baseline measles titer group as a fixed factor.

Comparison groups

Baseline measles titer percentile 25 to 50% v Baseline measles titer percentile 50 to 75%

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5924

Method

ANOVA

Parameter type

Geometric mean ratio

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

3.5

25 to 50% vs 75 to 100%

Statistical analysis description

Analysis of variance was performed with baseline measles titer group as a fixed factor.

Comparison groups

Baseline measles titer percentile 25 to 50% v Baseline measles titer percentile 75 to 100%

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3122

Method

ANOVA

Parameter type

Geometric mean ratio

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

4.1

50 to 75% vs 75 to 100%

Statistical analysis description

Analysis of variance was performed with baseline measles titer group as a fixed factor.

Comparison groups

Baseline measles titer percentile 50 to 75% v Baseline measles titer percentile 75 to 100%

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9665

Method

ANOVA

Parameter type

Geometric mean ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

2.8

Adverse events

Top of page

Timeframe for reporting adverse events

32 - 36 weeks; Adverse events were collected in the period after the first vaccination until the last on site study visit.

Adverse event reporting additional description

Local and systemic solicited adverse events were collected via subject diary, for 7 days after each vaccination. As per the protocol, adverse events were analyzed per treatment group but were not assessed with respect to individual vaccinations.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Treatment Group A

Reporting group description

Participants received i.m. vaccinations with MV-CHIK low dose (5xE4 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Reporting group title

Treatment Group C

Reporting group description

Participants received i.m. vaccinations with MV-CHIK high dose (5xE5 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Reporting group title

Treatment Group B

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0. MV-CHIK low dose (5xE4 (± 0.5 log) TCID50 per 0.3 mL) on day 28 and MV-CHIK boosting dose on day 196.

Reporting group title

Treatment Group D

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0, MV-CHIK high dose (5xE5 (± 0.5 log) TCID50 per 0.3 mL) on study day 28 and MV-CHIK boosting dose on day 196.

Reporting group title

Treatment Group M1

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day -28, MV-CHIK on day 0 and 28 and placebo on day 168 and 196.

Reporting group title

Treatment Group M2

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day -28, placebo on day 0 and 28 and MV-CHIK on day 168 and 196.

Reporting group title

Control Group CV1, A/C

Reporting group description

Participants received i.m. vaccinations with Priorix® on study day 0 and 28, placebo on day 196.

Reporting group title

Control Group CV2, B/D

Reporting group description

Participants received i.m. vaccinations with placebo on study day 0, Priorix® on day 28 and one boosting dose with Priorix® on day 196.

Serious adverse events	Treatment Group A	Treatment Group C	Treatment Group B	Treatment Group D	Treatment Group M1	Treatment Group M2	Control Group CV1, A/C	Control Group CV2, B/D
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 51 (1.96%)	0 / 47 (0.00%)	2 / 47 (4.26%)	1 / 50 (2.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 16 (6.25%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Papillary thyroid cancer
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	1 / 50 (2.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ligament rupture
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	1 / 47 (2.13%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	1 / 47 (2.13%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Umbilical hernia
subjects affected / exposed	1 / 51 (1.96%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Type 2 diabetes mellitus
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Treatment Group A	Treatment Group C	Treatment Group B	Treatment Group D	Treatment Group M1	Treatment Group M2	Control Group CV1, A/C	Control Group CV2, B/D
Total subjects affected by non serious adverse events
subjects affected / exposed	40 / 51 (78.43%)	38 / 47 (80.85%)	36 / 47 (76.60%)	41 / 50 (82.00%)	15 / 18 (83.33%)	14 / 16 (87.50%)	14 / 18 (77.78%)	11 / 16 (68.75%)
Vascular disorders
Haematoma
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	1 / 47 (2.13%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0
General disorders and administration site conditions
Influenza like illness
subjects affected / exposed	13 / 51 (25.49%)	9 / 47 (19.15%)	9 / 47 (19.15%)	8 / 50 (16.00%)	2 / 18 (11.11%)	4 / 16 (25.00%)	4 / 18 (22.22%)	1 / 16 (6.25%)
occurrences all number	17	12	12	16	2	7	4	1
Fatigue
subjects affected / exposed	10 / 51 (19.61%)	13 / 47 (27.66%)	9 / 47 (19.15%)	14 / 50 (28.00%)	5 / 18 (27.78%)	4 / 16 (25.00%)	5 / 18 (27.78%)	3 / 16 (18.75%)
occurrences all number	15	19	20	25	10	9	9	5
Axillary pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Injection site erythema
subjects affected / exposed	6 / 51 (11.76%)	10 / 47 (21.28%)	5 / 47 (10.64%)	9 / 50 (18.00%)	2 / 18 (11.11%)	2 / 16 (12.50%)	2 / 18 (11.11%)	2 / 16 (12.50%)
occurrences all number	8	18	6	11	4	2	3	2
Injection site induration
subjects affected / exposed	5 / 51 (9.80%)	8 / 47 (17.02%)	6 / 47 (12.77%)	15 / 50 (30.00%)	2 / 18 (11.11%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	7	12	6	24	2	1	0	0
Injection site oedema
subjects affected / exposed	4 / 51 (7.84%)	3 / 47 (6.38%)	2 / 47 (4.26%)	4 / 50 (8.00%)	1 / 18 (5.56%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	8	4	2	6	2	1	0	0
Injection site pain
subjects affected / exposed	24 / 51 (47.06%)	30 / 47 (63.83%)	21 / 47 (44.68%)	39 / 50 (78.00%)	8 / 18 (44.44%)	7 / 16 (43.75%)	6 / 18 (33.33%)	5 / 16 (31.25%)
occurrences all number	51	71	37	119	29	18	12	7
Injection site pruritus
subjects affected / exposed	0 / 51 (0.00%)	2 / 47 (4.26%)	1 / 47 (2.13%)	3 / 50 (6.00%)	0 / 18 (0.00%)	2 / 16 (12.50%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	4	1	4	0	2	0	0
Pyrexia
subjects affected / exposed	3 / 51 (5.88%)	0 / 47 (0.00%)	1 / 47 (2.13%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	3	0	1	0	0	1	1	0
Immune system disorders
Seasonal allergy
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	1 / 47 (2.13%)	1 / 50 (2.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	1	2	1	0	0	0
Reproductive system and breast disorders
Dysmenorrhoea
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	1 / 47 (2.13%)	1 / 47 (2.13%)	2 / 50 (4.00%)	2 / 18 (11.11%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	2	2	3	8	4	1	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	4 / 47 (8.51%)	1 / 47 (2.13%)	1 / 50 (2.00%)	2 / 18 (11.11%)	1 / 16 (6.25%)	1 / 18 (5.56%)	1 / 16 (6.25%)
occurrences all number	1	5	1	1	3	1	1	1
Cough
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	1 / 47 (2.13%)	2 / 47 (4.26%)	0 / 50 (0.00%)	1 / 18 (5.56%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	1	1	2	0	1	1	1	0
Dysphonia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	1 / 47 (2.13%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0
Sneezing
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Injury, poisoning and procedural complications
Injury
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	1 / 47 (2.13%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	1	0	0	0	0	0	1
Skin abrasion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	1 / 50 (2.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0
Contusion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	20 / 51 (39.22%)	14 / 47 (29.79%)	16 / 47 (34.04%)	17 / 50 (34.00%)	9 / 18 (50.00%)	8 / 16 (50.00%)	10 / 18 (55.56%)	6 / 16 (37.50%)
occurrences all number	36	30	32	47	18	19	19	13
Blood and lymphatic system disorders
Lymphadenopathy
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 51 (3.92%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	2	0	0	0	0	0	1	0
Ear and labyrinth disorders
Ear pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	1 / 47 (2.13%)	0 / 47 (0.00%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	0	0	3	0	0	0
Vertigo
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	2 / 16 (12.50%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Eye disorders
Dry eye
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Eye pruritus
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Gastrointestinal disorders
Abdominal pain upper
alternative assessment type: Non-systematic
subjects affected / exposed	3 / 51 (5.88%)	2 / 47 (4.26%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)
occurrences all number	3	2	0	0	0	0	0	1
Diarrhoea
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	0 / 47 (0.00%)	1 / 47 (2.13%)	1 / 50 (2.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	1	0	1	1	1	0	1	0
Abdominal pain
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	0 / 47 (0.00%)	1 / 47 (2.13%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	1	0	1	0	0	2	1	0
Toothache
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	0 / 47 (0.00%)	0 / 47 (0.00%)	1 / 50 (2.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	1	0	0	1	0	1	1	0
Nausea
subjects affected / exposed	8 / 51 (15.69%)	2 / 47 (4.26%)	2 / 47 (4.26%)	6 / 50 (12.00%)	2 / 18 (11.11%)	1 / 16 (6.25%)	4 / 18 (22.22%)	2 / 16 (12.50%)
occurrences all number	10	2	3	7	2	3	7	2
Vomiting
subjects affected / exposed	0 / 51 (0.00%)	1 / 47 (2.13%)	0 / 47 (0.00%)	1 / 50 (2.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	0	1	0	1	0	0	1	0
Skin and subcutaneous tissue disorders
Dermatitis contact
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	0 / 47 (0.00%)	0 / 47 (0.00%)	1 / 50 (2.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	1	0	0	1	0	0	2	0
Rash
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	3 / 47 (6.38%)	1 / 50 (2.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	2 / 18 (11.11%)	0 / 16 (0.00%)
occurrences all number	0	0	3	8	1	0	2	0
Erythema multiforme
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Renal and urinary disorders
Hypertonic bladder
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Back pain
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 51 (3.92%)	2 / 47 (4.26%)	2 / 47 (4.26%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	1 / 16 (6.25%)
occurrences all number	2	3	2	0	0	1	0	1
Myalgia
subjects affected / exposed	9 / 51 (17.65%)	5 / 47 (10.64%)	6 / 47 (12.77%)	13 / 50 (26.00%)	4 / 18 (22.22%)	1 / 16 (6.25%)	5 / 18 (27.78%)	2 / 16 (12.50%)
occurrences all number	12	7	9	22	8	2	8	2
Musculoskeletal pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	1 / 47 (2.13%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0
Bursitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Muscle spasms
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Arthralgia
subjects affected / exposed	8 / 51 (15.69%)	2 / 47 (4.26%)	5 / 47 (10.64%)	7 / 50 (14.00%)	2 / 18 (11.11%)	3 / 16 (18.75%)	3 / 18 (16.67%)	2 / 16 (12.50%)
occurrences all number	9	2	7	11	3	3	3	2
Arthritis reactive
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	1
Intervertabral disc protrustion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	1 / 47 (2.13%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	0	2	0	0	0	0	1	0
Limb discomfort
subjects affected / exposed	7 / 51 (13.73%)	4 / 47 (8.51%)	5 / 47 (10.64%)	11 / 50 (22.00%)	1 / 18 (5.56%)	1 / 16 (6.25%)	3 / 18 (16.67%)	2 / 16 (12.50%)
occurrences all number	7	4	7	19	1	1	3	2
Infections and infestations
Nasopharyngitis
alternative assessment type: Non-systematic
subjects affected / exposed	7 / 51 (13.73%)	4 / 47 (8.51%)	4 / 47 (8.51%)	4 / 50 (8.00%)	2 / 18 (11.11%)	1 / 16 (6.25%)	2 / 18 (11.11%)	2 / 16 (12.50%)
occurrences all number	7	5	4	5	5	1	2	3
Rhinitis
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 51 (3.92%)	3 / 47 (6.38%)	0 / 47 (0.00%)	2 / 50 (4.00%)	2 / 18 (11.11%)	2 / 16 (12.50%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	2	3	0	2	3	2	1	0
Upper respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	3 / 51 (5.88%)	1 / 47 (2.13%)	3 / 47 (6.38%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	3	2	4	0	0	0	1	0
Urinary tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	1 / 47 (2.13%)	1 / 47 (2.13%)	0 / 50 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)
occurrences all number	1	1	1	0	0	0	1	0
Gingivitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Hordeolum
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Vaginal infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Vulvovaginal candidiasis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Cystitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	1 / 50 (2.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0
Gastroenteritis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	2 / 47 (4.26%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	2	0	0	1	0	0
Otitis externa
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 51 (1.96%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0
Tonsillitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	1 / 47 (2.13%)	1 / 47 (2.13%)	0 / 50 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	1	1	0	0	1	0	0
Metabolism and nutrition disorders
Appetite disorder
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 51 (0.00%)	0 / 47 (0.00%)	0 / 47 (0.00%)	0 / 50 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0

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Were there any global substantial amendments to the protocol? Yes

02 Aug 2016

Protocol Amendment 1 (substantial, dated 26-Apr-2016) incorporated in Protocol version 1.3 (26-Apr-2016) before the first study submission. The protocol was amended:  To precisely define the primary endpoint as immunogenicity on Day 56 for all treatment groups  To adapt the study design (by shifting study visits) to enable immunogenicity measurements on Day 56 for all treatment groups  To change the definition from three cohorts consisting of two different treatment regimens each, to a more reasonable definition of six treatment groups  To define the dates of study visits based on an interval of 28 days and to rename the study days as follows: Screening Visit on Study Day -35; Visit 0 on Study Day -28; Visit 1 on Study Day 0; Visit 2 on Study Day 28; Visit 3 on Study Day 56; Visit 4 on Study Day 168; Visit 5 on Study Day 196; Visit 6 on Study Day 224  To state the study objectives more precisely  To include a preliminary data analysis  To describe the role of the DSMB  To remove the safety assessment by telephone call, 12 months after the first vaccination  To clarify that the control-vaccine Priorix® can be exchanged by MMR-Vax-Pro® or equal measles vaccine In addition, to correct typos, include some formal changes and update the list of abbreviations

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:
Double blinded, randomized, Priorix®- and placebo-controlled, trial to evaluate the optimal dose of MV-CHIK vaccine (against Chikungunya virus) in regard to immunogenicity, safety and tolerability in healthy volunteers

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Functional Anti-chikungunya Antibody Titers on Day 56 (28 Days Post Immunisation) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

Primary: Functional Anti-chikungunya Antibody Titers on Day 56 (28 Days Post Immunisation) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

Secondary: Functional Anti-Chikungunya Antibody Titers on Days 0, 28, 196 and 224 (M1/M2 Groups Day 168) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

Secondary: Functional Anti-Chikungunya Antibody Titers on Days 0, 28, 196 and 224 (M1/M2 Groups Day 168) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

Secondary: Measurement of Anti-measles Antibody Titer by Enzyme Linked Immunosorbent Assay

Secondary: Measurement of Anti-measles Antibody Titer by Enzyme Linked Immunosorbent Assay

Secondary: Number of Participants With Solicited Local and Systemic Adverse Events

Secondary: Number of Participants With Solicited Local and Systemic Adverse Events

Secondary: Number of participants who experienced treatment emergent adverse events

Secondary: Number of participants who experienced treatment emergent adverse events

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Urine Until Day 196

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Urine Until Day 196

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Saliva Until Day 196

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Saliva Until Day 196

Secondary: Chikungunya Virus Specific T Cell Responses

Secondary: Chikungunya Virus Specific T Cell Responses

Secondary: Immunogenicity confirmed by the presence of humoral anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA)

Secondary: Immunogenicity confirmed by the presence of humoral anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA)

Secondary: Functional anti-chikungunya antibody titers on day 56 (28 days post immunization) by baseline measles titer

Secondary: Functional anti-chikungunya antibody titers on day 56 (28 days post immunization) by baseline measles titer

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: Double blinded, randomized, Priorix®- and placebo-controlled, trial to evaluate the optimal dose of MV-CHIK vaccine (against Chikungunya virus) in regard to immunogenicity, safety and tolerability in healthy volunteers

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Functional Anti-chikungunya Antibody Titers on Day 56 (28 Days Post Immunisation) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

Primary: Functional Anti-chikungunya Antibody Titers on Day 56 (28 Days Post Immunisation) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

Secondary: Functional Anti-Chikungunya Antibody Titers on Days 0, 28, 196 and 224 (M1/M2 Groups Day 168) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

Secondary: Functional Anti-Chikungunya Antibody Titers on Days 0, 28, 196 and 224 (M1/M2 Groups Day 168) Confirmed by Plaque Reduction Neutralization Test (PRNT50)

Secondary: Measurement of Anti-measles Antibody Titer by Enzyme Linked Immunosorbent Assay

Secondary: Measurement of Anti-measles Antibody Titer by Enzyme Linked Immunosorbent Assay

Secondary: Number of Participants With Solicited Local and Systemic Adverse Events

Secondary: Number of Participants With Solicited Local and Systemic Adverse Events

Secondary: Number of participants who experienced treatment emergent adverse events

Secondary: Number of participants who experienced treatment emergent adverse events

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Urine Until Day 196

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Urine Until Day 196

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Saliva Until Day 196

Secondary: Number of Participants With Shedding of Live Recombinant Virus in Saliva Until Day 196

Secondary: Chikungunya Virus Specific T Cell Responses

Secondary: Chikungunya Virus Specific T Cell Responses

Secondary: Immunogenicity confirmed by the presence of humoral anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA)

Secondary: Immunogenicity confirmed by the presence of humoral anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA)

Secondary: Functional anti-chikungunya antibody titers on day 56 (28 days post immunization) by baseline measles titer

Secondary: Functional anti-chikungunya antibody titers on day 56 (28 days post immunization) by baseline measles titer

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Double blinded, randomized, Priorix®- and placebo-controlled, trial to evaluate the optimal dose of MV-CHIK vaccine (against Chikungunya virus) in regard to immunogenicity, safety and tolerability in healthy volunteers