Efficacy of MVA-NP+M1 in the Influenza H3N2 Human Challenge Model

• Sponsor: Vaccitech (UK) Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03883113
• Collaborator: (none)
• Enrollment: 145
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.5
• Patients Per Site Per Month: 13.8

Study Details

Study Description

Brief Summary

A Phase 2, single center, randomized, double blind study evaluating the safety, efficacy, and immunogenicity of MVA NP+M1 in the H3N2 human influenza challenge model; on healthy adult volunteers.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: MVA-NP+M1; Biological: Saline; Biological: H3N2 (A/Belgium/2417/2015)	Phase 2

Detailed Description

The study consists of an outpatient vaccination phase (155 participants), and at least 2 months later an inpatient challenge phase (134 participants). Participants are randomized 93:62 to receive either MVA-NP+M1 or Placebo. Up to 20 participants will be challenged over several 3-week blocks, and the remainder at the final 3-week block for a total of 80 MVA-NP+M1 and 54 Placebo recipients challenged.

Study Design

• Study Type: Interventional
• Actual Enrollment: 145 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Efficacy of MVA-NP+M1 in the Influenza H3N2 Human Challenge Model
• Actual Study Start Date: Jun 3, 2019
• Actual Primary Completion Date: Dec 16, 2019
• Actual Study Completion Date: Apr 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MVA-NP+M1 & H3N2 Challenge Virus Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml)	Biological: MVA-NP+M1; Trial Vaccine; Biological: H3N2 (A/Belgium/2417/2015); Challenge Agent
Placebo Comparator: Saline Placebo & H3N2 Challenge Virus Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml)	Biological: Saline; Sodium Chloride Placebo; Biological: H3N2 (A/Belgium/2417/2015); Challenge Agent

Outcome Measures

Primary Outcome Measures

1. Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR [Throughout 9 days (Day2, Day3, Day4, Day5, Day6, Day7, Day8, Day9, Day10) after viral Inoculation (Day1) of the challenge phase. Nasal swabs taken twice a day (b.i.d) at least 8 hours apart.]

   Measure of nasopharyngeal viral shedding during challenge; recorded as viral area under curve (vAUC) as determined by quantitative real time polymerase chain reaction (qRT-PCR). vAUC is calculated by plotting the log viral particles number/ml for each time point against time and is using the trapezoidal rule.

Secondary Outcome Measures

1. Number and Percentage of Virologically Confirmed Influenza-Like Illness [9 days from day 2 to day 10]

   Incidence (frequency tabulation) of laboratory-confirmed influenza-like illness compared between vaccine and placebo arms Virologically confirmed influenza-like illness (ILI) is defined as having respiratory or flu-like symptom occurring on two consecutive days, along with a positive qPCR or qCulture result.

2. Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR) [9 days from day 2 to day 10]

   The attack rate is defined as the percentage of inoculated participants with at least two consecutive positive swabs as determined by qRT-PCR within the timespan of two consecutive days

3. Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture) [9 days from day 2 to day 10]

   The attack rate is defined as the percentage of inoculated participants with at least two consecutive positive swabs as determined by qCulture within the timespan of two consecutive days

4. Time to Start of Viral Shedding (qPCR) From Virus Inoculation [9 days from day 2 to day 10]

   The Time to Start of Viral Shedding (qPCR) is calculated as (datetime of first of two positive swabs (qPCR) within 2 consecutive days - challenge datetime)/(60*60)

5. Time to Start of Viral Shedding (qCulture) From Virus Inoculation [9 days from day 2 to day 10]

   Time to Start of Viral Shedding (qCulture) is calculated as (datetime of first of two positive swabs (qCulture) within 2 consecutive days - challenge datetime)/(60*60)

6. Peak Viral Shedding (qPCR) After the Virus Inoculation [9 days from Day 2 to Day 10]

   This is measured by the highest viral load concentration by qPCR

7. Peak Viral Shedding (qCulture) After Virus Inoculation [9 days from day 2 to day 10]

   This is measured by the highest viral load concentration by qCulture.

8. Time to Peak of Viral Shedding (qPCR) From the Viral Inoculation [9 days from day 2 to day 10]

   This is calculated as (datetime of highest viral load concentration (qPCR) - challenge datetime)/(60*60)

9. Time to Peak of Viral Shedding (qCulture) From the Viral Inoculation [9 days from day 2 to day 10]

   This is calculated as (datetime of highest viral load concentration (qCulture) - challenge datetime)/(60*60)

10. Duration of Viral Shedding (qPCR) After the Virus Inoculation [9 days from day2 to day10]

    It is calculated as (datetime of first negative swab (qPCR) following the last positive swab (qPCR) - datetime of first positive of two positive swabs (qPCR) within 2 consecutive days)/(60*60)

11. Duration of Viral Shedding (qCulture) After the Virus Inoculation [9 days from day 2 to day 10]

    It is calculated as (datetime of first negative swab (qCulture) following the last positive swab (qCulture) - datetime of first positive of two positive swabs (qCulture) within 2 consecutive days)/(60*60)

12. Total Area Under the Curve (AUC) of Self-reported Influenza Total Symptom Score (SSC AUC) [11 days from Day 1 to Day 11]

    Total symptom scores were compared for MVA-NP+M1 vs. Placebo from Day1 to Day11 post-challenge as AUC of composite score. Symptoms were collected twice a day (lymphadenopathy once a day) on a Symptom Score Card(SSC). SSC recorded scores for each 16 general (gastrointestinal/body systemic) and 12 local (upper/lower respiratory tract) symptoms, on the scale per timepoint (for example Day2,AM). Participants rated the severity of symptoms, higher scores indicating a more severe symptom. The scores ranged from 0 to 3 (0:symptom free, 1:mild, 2:moderate, 3:severe).The SSC also contained the question whether the subject felt well to go to work "today" (yes/no). The Overall SSC score was calculated, as the Arithmetic Mean of the Scores collected across all 28 items on the card per Timepoint and ranged from 0 to maximum 3. The SSC AUC [0-11 days] was derived based on the Overall SSC score against time (*hour), using the linear trapezoidal rule and it ranged from 0 to 110 Score*hour.

13. Total Days of Fever [11 days from Day 1 to Day 11]

    Total days of fever for MVA-NP+M1 vs. Placebo

14. Average Total Mucus Production [11 days from Day 1 to Day 11]

    Total mucus weight of used tissue (regardless of take rate) for MVA-NP+M1 vs. Placebo. Total mucus production was only be calculated in case all tissues were returned (sum of clean and used tissues returned should be 20 tissues for each bag).

15. T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence [3 months (day 0, day 8 and day 28 of the vaccination period and day -1 and day 28 of the challenge period)]

    T Cell Response was assessed for IFN gamma and granzyme B, on the peripheral blood mononuclear cell using a double-colour enzymatic ELISpot assay. For each of them, three stimulation antigens were assessed: nucleoprotein NP, matrix1 M1 and a negative control, dimethyl sulfoxide (DMSO). The number of spot-forming T cell colonies per well (i.e. 200,000 cells) +/- standard deviation for the total response to NP+M1 is reported. The endpoint was recorded as the mean spot-forming units per million peripheral blood mononuclear cells in the peptide-stimulated wells minus the mean DMSO control wells for the sample. T cell responses over time (sampling timepoints) were then assessed in relation to the primary endpoint, symptom scores, and influenza incidence.

16. Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms [7 days following vaccination]

    Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination; self-reported symptoms recorded using paper diaries

17. Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms [17 days following vaccination]

    Occurrence of solicited local and systemic reactogenicity signs and symptoms; self-reported symptoms recorded using questionnaires and adverse event monitoring

Other Outcome Measures

1. Severity of Individual Symptoms for MVA-NP+M1 vs. Placebo [11 days]

   Severity of individual self-reported symptoms for MVA-NP+M1 vs. Placebo

2. Total Symptom Score Time to Start, Time to Peak and Duration [11 days]

   Time to start; time to peak and duration of total self-reported symptom score, regardless of take rate Influenza Symptom Score Card of FLU010 - Solicited symptoms for generalized, and upper and lower respiratory tract symptoms scored by severity (0: absent, 1: mild, 2: moderate, or 3: severe).

3. Correlation of T Cell Phenotypes With Illness Outcomes [3 months]

   Correlation of antigen specific T Cell phenotypes with illness outcomes

4. Vaccination Effect on Antibody Responses by ELISpot and ICS Assays [3 months]

   Antibody responses of MVA-NP+M1 vs Placebo following influenza challenge measured by ELISpot and Intracellular Cytokine Staining (ICS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy males and females aged ≥18 and ≤55 years of age at the point of enrolment.

• Non-smokers or those who stopped smoking ≥ 3 months prior to screening 1 visit.

• Willingness to remain in isolation for the duration of the study.

• A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the following:

1. Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).

2. Of childbearing potential but has been and agrees to continue practicing highly effective contraception or abstinence (if this is the preferred and usual lifestyle of the participant) from 6 months prior to vaccination to 6 months after administration of the influenza challenge virus. Highly effective methods of contraception include 1 or more of the following:

1. male partner who is sterile (vasectomised) prior to the female participants entry into the study and is the sole sexual partner for the female participant; ii. hormonal (oral, intravaginal, transdermal, implantable or injectable); iii. an intrauterine hormone-releasing system (IUS); iv. an intrauterine device (IUD) with a documented failure rate of < 1%; v. bilateral tubal occlusion.

• Pre-challenge serum microneutralization test (MNT) against A/Belgium/4217/2015 (H3N2) challenge strain < 20.

Exclusion Criteria:

• BMI < 19 and > 32.

• Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness including a history of chronic respiratory illness.

• History of seasonal hay fever or a clinically significant seasonal allergic rhinitis (SAR), including the use of symptomatic prescription only medication and non-prescription medication.

• History or evidence of autoimmune disease or known immunodeficiency of any cause - with the exception of atopic dermatitis/eczema and atopic rhinitis.

• Any history of anaphylaxis in reaction to vaccination or history of allergic reactions likely to be exacerbated by any component of the vaccine.

• History of lung disease (Asthma, COPD).

• Current smokers or those who stopped smoking < 3months prior to screening 1 visit.

• Positive diagnostic tests for HIV, Hepatitis B or Hepatitis C indicating active infection.

• Evidence of drug abuse or a positive urine drug screen or alcohol breath test.

• Chronic use of any medication or other product (prescription or over-the-counter), for symptoms of rhinitis or nasal congestion or for any chronic nasopharyngeal complaint, or chronic use of any intranasal medication for any indication that has not ceased within 30 days prior to screening 1.

• Receipt of any investigational drug within 3 months prior to vaccination, or prior participation in a clinical trial of any influenza vaccine, or any investigational vaccine or experimental influenza viral challenge delivered directly to the respiratory tract within 1 year prior to challenge.

• Receipt of the 2018/2019 seasonal flu vaccine.

• Receipt of any live vaccines within the 4 weeks prior to vaccination.

• Any laboratory test which is abnormal and which is deemed by the Investigator(s) to be clinically significant.

• Receipt of any systemic chemotherapy agent at any time.

• Physician reported influenza or a syndrome consistent with influenza (as judged by the investigator) in the previous 6 months.

• Known allergy to treatments for influenza (including but not limited to oseltamivir).

• History of frequent epistaxis (nose bleeds).

• Any nasal or sinus surgery within 6 months of Viral Challenge or any significant abnormality, either of which results in alteration of the anatomy of the nose or nasopharynx (including significant nasal polyps).

• Volunteers with household contacts who are at risk for serious or severe complications of influenza disease including, but not limited to: persons ≥ 65 years; presence of significant chronic cardiopulmonary, metabolic, renal, or neurological conditions; immunosuppression due to any condition or therapies; BMI >40.

• Participants that are an employee or family member of the Investigator or study site personnel may not be enrolled.

• Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.

EXCLUSION (CHALLENGE PERIOD ONLY)

• Abnormal spirometry assessed to be clinically significant.

• Known close contact with anyone known to have influenza in the past 7 days at the time of quarantine.

• Influenza-like illness (ILI) symptoms as assessed at the admission to clinic on Day -2 prior to challenge.

• Presence of fever, defined as participant presenting with a temperature reading of > 38.0°C on admission to quarantine.

• Qualitative Polymerase chain reaction (PCR) results positive for viral infection. However, participants may be included into later challenge cohort.

• Acute use of any medication or other product, prescription or over-the-counter, for symptoms of rhinitis or nasal congestion within 7 days prior to challenge. This includes any oral corticosteroid or beta agonist containing nasal spray.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SGS Life Sciences, Clinical Pharmacology Unit (CPU)	Antwerp		Belgium	2060

Sponsors and Collaborators

• Vaccitech (UK) Limited

Investigators

• Principal Investigator: Robin Rogiers, MD, SGS S.A.

Study Documents (Full-Text)

• Study Protocol - Jul 10, 2019
• Statistical Analysis Plan - Jun 15, 2020

More Information

Publications

None provided.

• Responsible Party: Vaccitech (UK) Limited
• ClinicalTrials.gov Identifier: NCT03883113
• Other Study ID Numbers: FLU010
• First Posted: Mar 20, 2019
• Last Update Posted: Mar 18, 2021
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	The study was conducted at the SGS Clinical Pharmacology Unit in Antwerp, Belgium.
Pre-assignment Detail	Eight-hundred and nineteen (819) subjects were screened. One hundred and forty-five (145) subjects were actually enrolled and vaccinated. The study consisted of an outpatient vaccination phase and at least 6 weeks later an inpatient challenge phase.

Arm/Group Title	MVA-NP+M1 & H3N2 Challenge Virus	Saline Placebo & H3N2 Challenge Virus
Arm/Group Description	Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml) MVA-NP+M1: Trial Vaccine H3N2 (A/Belgium/2417/2015): Challenge Agent	Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml) Saline: Sodium Chloride Placebo H3N2 (A/Belgium/2417/2015): Challenge Agent
Period Title: Overall Study
STARTED	87	58
COMPLETED	71	46
NOT COMPLETED	16	12

Baseline Characteristics

Arm/Group Title	MVA-NP+M1 & H3N2 Challenge Virus	Saline Placebo & H3N2 Challenge Virus	Total
Arm/Group Description	Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml) MVA-NP+M1: Trial Vaccine H3N2 (A/Belgium/2417/2015): Challenge Agent	Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml) Saline: Sodium Chloride Placebo H3N2 (A/Belgium/2417/2015): Challenge Agent	Total of all reporting groups
Overall Participants	87	58	145
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	87 100%	58 100%	145 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	43.00	41.25	42.50
Sex: Female, Male (Count of Participants)
Female	47 54%	31 53.4%	78 53.8%
Male	40 46%	27 46.6%	67 46.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	2 2.3%	0 0%	2 1.4%
Black or African American	4 4.6%	0 0%	4 2.8%
Middle Eastern	0 0%	1 1.7%	1 0.7%
White	81 93.1%	57 98.3%	138 95.2%
Region of Enrollment (participants) [Number]
Belgium	87 100%	58 100%	145 100%
Smoking Status (Count of Participants)
Ex-smoker	27 31%	18 31%	45 31%
Non-smoker	60 69%	40 69%	100 69%
Height (cm) [Median (Full Range) ]
Median (Full Range) [cm]	172.40	172.30	172.40
Weight (kg) [Median (Full Range) ]
Median (Full Range) [kg]	72.9	75.15	73.60
BMI (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	24.7	25.5	24.90

Outcome Measures

1. Primary Outcome

Title	Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR
Description	Measure of nasopharyngeal viral shedding during challenge; recorded as viral area under curve (vAUC) as determined by quantitative real time polymerase chain reaction (qRT-PCR). vAUC is calculated by plotting the log viral particles number/ml for each time point against time and is using the trapezoidal rule.
Time Frame	Throughout 9 days (Day2, Day3, Day4, Day5, Day6, Day7, Day8, Day9, Day10) after viral Inoculation (Day1) of the challenge phase. Nasal swabs taken twice a day (b.i.d) at least 8 hours apart.

Outcome Measure Data

Analysis Population Description

End point values

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)	MVA-NP+M1 (PP)	Placebo (PP)	MVA-NP+M1 (Challenge)	Placebo (Challenge)
Arm/Group Description	Intention-to-treat (the actually challenged with the virus)	Intention-to-treat (the actually challenged with the virus)	Per protocol analysis set	Per protocol analysis set	Safety Analysis Set (challenged participants)	Safety Analysis Set (challenged participants)
Measure Participants	71	47	70	47	71	47
Least Squares Mean (95% Confidence Interval) [hour*Log10 Viral Particles/ ml]	649.7	726.1	646.5	726.1	649.7	726.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1711
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (PP), Placebo (PP)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1654
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (Challenge), Placebo (Challenge)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1711
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Number and Percentage of Virologically Confirmed Influenza-Like Illness
Description	Incidence (frequency tabulation) of laboratory-confirmed influenza-like illness compared between vaccine and placebo arms Virologically confirmed influenza-like illness (ILI) is defined as having respiratory or flu-like symptom occurring on two consecutive days, along with a positive qPCR or qCulture result.
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
Virologically confirmed Influenza-like Illness	43 49.4%	29 50%
No Virologically Confirmed Influenza-like Illness	28 32.2%	18 31%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments	The statistical analysis applies to participants with Virologically confirmed Influenza-like Illness versus participants without Virologically confirmed Influenza-like Illness
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR)
Description	The attack rate is defined as the percentage of inoculated participants with at least two consecutive positive swabs as determined by qRT-PCR within the timespan of two consecutive days
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
qPCR-confirmed influenza	90.1 103.6%	97.9 168.8%
No qPCR influenza	9.9 11.4%	2.1 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments	This statistical analysis applies to participants with qPCR confirmed Influenza versus participants with no qPCR confirmed Influenza
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.143
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture)
Description	The attack rate is defined as the percentage of inoculated participants with at least two consecutive positive swabs as determined by qCulture within the timespan of two consecutive days
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
qCulture confirmed influenza	77.5	85.1
No qCulture-confirmed influenza	22.5	14.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments	This statistical analysis applies to participants with qCulture confirmed Influenza versus participants without qCulture confirmed Influenza
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3504
	Comments
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Time to Start of Viral Shedding (qPCR) From Virus Inoculation
Description	The Time to Start of Viral Shedding (qPCR) is calculated as (datetime of first of two positive swabs (qPCR) within 2 consecutive days - challenge datetime)/(60*60)
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

[MVA-NP+M1 (ITT)] - subjects assessed = 71 subjects with event = 64 subjects censored = 7 [Placebo (ITT)] - subjects assessed = 47 subjects with event = 46 subjects censored = 1

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
Median (95% Confidence Interval) [hours]	24.40	24.30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5558
	Comments
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Time to Start of Viral Shedding (qCulture) From Virus Inoculation
Description	Time to Start of Viral Shedding (qCulture) is calculated as (datetime of first of two positive swabs (qCulture) within 2 consecutive days - challenge datetime)/(60*60)
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

[MVA-NP+M1(ITT)] - Subjects assessed = 71 Subjects with event = 55 Subjects censored = 16; [Placebo (ITT)] - Subjects assessed = 47 Subjects with event = 40 Subjects censored = 7

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
Median (95% Confidence Interval) [hours]	35.9	47.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6534
	Comments
	Method	Log Rank
	Comments

7. Secondary Outcome

Title	Peak Viral Shedding (qPCR) After the Virus Inoculation
Description	This is measured by the highest viral load concentration by qPCR
Time Frame	9 days from Day 2 to Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (ITT) Successful Attack	Placebo (ITT) Successful Attack
Arm/Group Description	Subset of participants who received MVA-NP+M1 and with a successful attack	Subset of participants who received Placebo and with a successful attack
Measure Participants	64	46
Mean (95% Confidence Interval) [Log10 Viral Particles/ ml]	5.876	6.054

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5485
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Peak Viral Shedding (qCulture) After Virus Inoculation
Description	This is measured by the highest viral load concentration by qCulture.
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (ITT) Successful Attack	Placebo (ITT) Successful Attack
Arm/Group Description	Subset of participants who received MVA-NP+M1 and with a successful attack	Subset of participants who received Placebo and with a successful attack
Measure Participants	55	40
Mean (95% Confidence Interval) [Log10 Viral Particles/ ml]	4.073	4.069

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6753
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Time to Peak of Viral Shedding (qPCR) From the Viral Inoculation
Description	This is calculated as (datetime of highest viral load concentration (qPCR) - challenge datetime)/(60*60)
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

[MVA-NP+M1 (ITT)] - Subjects assessed = 71 Subjects with event = 64 Subjects censored = 7; [Placebo (ITT)] - Subjects assessed = 47 Subjects with event = 46 Subjects censored = 1

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
Median (95% Confidence Interval) [hours]	72.20	107.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.711
	Comments
	Method	Log Rank
	Comments

10. Secondary Outcome

Title	Time to Peak of Viral Shedding (qCulture) From the Viral Inoculation
Description	This is calculated as (datetime of highest viral load concentration (qCulture) - challenge datetime)/(60*60)
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

[MVA-NP+M1 (ITT)] - Subjects assessed = 71 Subjects with event = 55 Subjects censored = 16; [Placebo (ITT)] - Subjects assessed = 47 Subjects with event = 40 Subjects censored = 7

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
Median (95% Confidence Interval) [hours]	83.40	83.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4689
	Comments
	Method	Log Rank
	Comments

11. Secondary Outcome

Title	Duration of Viral Shedding (qPCR) After the Virus Inoculation
Description	It is calculated as (datetime of first negative swab (qPCR) following the last positive swab (qPCR) - datetime of first positive of two positive swabs (qPCR) within 2 consecutive days)/(60*60)
Time Frame	9 days from day2 to day10

Outcome Measure Data

Analysis Population Description

This endpoint is only calculated for the subset of participants with a successful attack.

Arm/Group Title	MVA-NP+M1 (ITT) Successful Attack	Placebo (ITT) Successful Attack
Arm/Group Description	Subset of participants who received MVA-NP+M1 and with a successful attack	Subset of participants who received Placebo and with a successful attack
Measure Participants	64	46
Mean (95% Confidence Interval) [hours]	170.80	172.47

12. Secondary Outcome

Title	Duration of Viral Shedding (qCulture) After the Virus Inoculation
Description	It is calculated as (datetime of first negative swab (qCulture) following the last positive swab (qCulture) - datetime of first positive of two positive swabs (qCulture) within 2 consecutive days)/(60*60)
Time Frame	9 days from day 2 to day 10

Outcome Measure Data

Analysis Population Description

This endpoint is only calculated for the subset of participants with a successful attack

Arm/Group Title	MVA-NP+M1 (ITT) Successful Attack	Placebo (ITT) Successful Attack
Arm/Group Description	Subset of participants who received MVA-NP+M1 and with a successful attack	Subset of participants who received Placebo and with a successful attack
Measure Participants	55	40
Mean (95% Confidence Interval) [hours]	118.19	121.78

13. Secondary Outcome

Title	Total Area Under the Curve (AUC) of Self-reported Influenza Total Symptom Score (SSC AUC)
Description	Total symptom scores were compared for MVA-NP+M1 vs. Placebo from Day1 to Day11 post-challenge as AUC of composite score. Symptoms were collected twice a day (lymphadenopathy once a day) on a Symptom Score Card(SSC). SSC recorded scores for each 16 general (gastrointestinal/body systemic) and 12 local (upper/lower respiratory tract) symptoms, on the scale per timepoint (for example Day2,AM). Participants rated the severity of symptoms, higher scores indicating a more severe symptom. The scores ranged from 0 to 3 (0:symptom free, 1:mild, 2:moderate, 3:severe).The SSC also contained the question whether the subject felt well to go to work "today" (yes/no). The Overall SSC score was calculated, as the Arithmetic Mean of the Scores collected across all 28 items on the card per Timepoint and ranged from 0 to maximum 3. The SSC AUC [0-11 days] was derived based on the Overall SSC score against time (*hour), using the linear trapezoidal rule and it ranged from 0 to 110 Score*hour.
Time Frame	11 days from Day 1 to Day 11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
Geometric Mean (95% Confidence Interval) [Composite symptom score on scale*hour]	16.709	20.432

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	Total Days of Fever
Description	Total days of fever for MVA-NP+M1 vs. Placebo
Time Frame	11 days from Day 1 to Day 11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
Mean (95% Confidence Interval) [days]	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6799
	Comments
	Method	zero-inflated poisson model
	Comments

15. Secondary Outcome

Title	Average Total Mucus Production
Description	Total mucus weight of used tissue (regardless of take rate) for MVA-NP+M1 vs. Placebo. Total mucus production was only be calculated in case all tissues were returned (sum of clean and used tissues returned should be 20 tissues for each bag).
Time Frame	11 days from Day 1 to Day 11

Outcome Measure Data

Analysis Population Description

Total mucus production was only calculated for challenge cohorts 5 to 8 and only if all tissues (cleaned or used) were returned.

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	26	18
Mean (95% Confidence Interval) [grams]	31.09	38.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVA-NP+M1 (ITT), Placebo (ITT)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5911
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

16. Secondary Outcome

Title	T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence
Description	T Cell Response was assessed for IFN gamma and granzyme B, on the peripheral blood mononuclear cell using a double-colour enzymatic ELISpot assay. For each of them, three stimulation antigens were assessed: nucleoprotein NP, matrix1 M1 and a negative control, dimethyl sulfoxide (DMSO). The number of spot-forming T cell colonies per well (i.e. 200,000 cells) +/- standard deviation for the total response to NP+M1 is reported. The endpoint was recorded as the mean spot-forming units per million peripheral blood mononuclear cells in the peptide-stimulated wells minus the mean DMSO control wells for the sample. T cell responses over time (sampling timepoints) were then assessed in relation to the primary endpoint, symptom scores, and influenza incidence.
Time Frame	3 months (day 0, day 8 and day 28 of the vaccination period and day -1 and day 28 of the challenge period)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (ITT)	Placebo (ITT)
Arm/Group Description	Intention-to-treat	Intention-to-treat
Measure Participants	71	47
Baseline (Vaccination)	230 (265)	167 (157)
Day 8 (from Vaccination)	645 (634)	170 (144)
Day 28 (from Vaccination)	566 (551)	163 (160)
Day 0 Challenge Period	460 (471)	159 (132)
Day 28 Challenge Period	561 (483)	329 (220)

17. Secondary Outcome

Title	Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms
Description	Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination; self-reported symptoms recorded using paper diaries
Time Frame	7 days following vaccination

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	MVA-NP+M1	Saline Placebo
Arm/Group Description	Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml) MVA-NP+M1: Trial Vaccine	Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml) Saline: Sodium Chloride Placebo
Measure Participants	87	58
TEAE	36 41.4%	18 31%
Solicited symptom	84 96.6%	24 41.4%
TEAE or solicited symptom	85 97.7%	34 58.6%
Local solicited symptom	80 92%	8 13.8%
Local Grade 3 solicited symptom	2 2.3%	0 0%
Systemic solicited symptom	72 82.8%	20 34.5%
Systemic Grade 3 solicited symptom	2 2.3%	0 0%
TEAE of special interest	0 0%	0 0%
Serious TEAE	1 1.1%	0 0%
Non-serious TEAE	36 41.4%	18 31%
Grade ≥3 TEAE	1 1.1%	0 0%
Grade ≥3 TE laboratory toxicity	2 2.3%	0 0%
Fatal TEAE	0 0%	0 0%
TEAE related to treatment	10 11.5%	4 6.9%
Serious TEAE related to treatment	1 1.1%	0 0%
Grade ≥3 TEAE related to treatment	1 1.1%	0 0%
TEAE for which the study was discontinued	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms
Description	Occurrence of solicited local and systemic reactogenicity signs and symptoms; self-reported symptoms recorded using questionnaires and adverse event monitoring
Time Frame	17 days following vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVA-NP+M1 (Challenge)	Placebo (Challenge)
Arm/Group Description	Safety Analysis Set (challenged participants)	Safety Analysis Set (challenged participants)
Measure Participants	71	47
TEAE	30 34.5%	21 36.2%
Solicited symptom	62 71.3%	40 69%
TEAE or solicited symptom	65 74.7%	42 72.4%
Local solicited symptom	59 67.8%	39 67.2%
Local Grade 3 solicited symptom	0 0%	0 0%
Systemic solicited symptom	45 51.7%	32 55.2%
Systemic Grade 3 solicited symptom	0 0%	0 0%
TEAE of special interest	0 0%	0 0%
Serious TEAE	0 0%	1 1.7%
Non-serious TEAE	30 34.5%	20 34.5%
Grade ≥3 TEAE	0 0%	2 3.4%
Grade ≥3 TE laboratory toxicity	7 8%	2 3.4%
Fatal TEAE	0 0%	0 0%
TEAE related to challenge	7 8%	5 8.6%
Serious TEAE related to challenge	0 0%	0 0%
Grade ≥3 TEAE related to challenge	0 0%	0 0%
TEAE for which the study was discontinued	0 0%	1 1.7%

19. Other Pre-specified Outcome

Title	Severity of Individual Symptoms for MVA-NP+M1 vs. Placebo
Description	Severity of individual self-reported symptoms for MVA-NP+M1 vs. Placebo
Time Frame	11 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Other Pre-specified Outcome

Title	Total Symptom Score Time to Start, Time to Peak and Duration
Description	Time to start; time to peak and duration of total self-reported symptom score, regardless of take rate Influenza Symptom Score Card of FLU010 - Solicited symptoms for generalized, and upper and lower respiratory tract symptoms scored by severity (0: absent, 1: mild, 2: moderate, or 3: severe).
Time Frame	11 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

21. Other Pre-specified Outcome

Title	Correlation of T Cell Phenotypes With Illness Outcomes
Description	Correlation of antigen specific T Cell phenotypes with illness outcomes
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Other Pre-specified Outcome

Title	Vaccination Effect on Antibody Responses by ELISpot and ICS Assays
Description	Antibody responses of MVA-NP+M1 vs Placebo following influenza challenge measured by ELISpot and Intracellular Cytokine Staining (ICS)
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Any time during the study from the first administration of any study drug until the last study-related activity (the outpatient visit at 27 days ±3 days following the challenge or 6 months following vaccination ±14 days, whichever is longer)
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAE) are defined as the Adverse Events starting during or after first administration of any study drug to the end of the study independently of their intensity and if they are related or not to the study drug.
Arm/Group Title	MVA-NP+M1 (Vaccination Phase)		Saline Placebo (Vaccination Phase)		MVA-NP+M1 (Challenge Phase)		Saline Placebo (Challenge Phase)
Arm/Group Description	Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.); MVA-NP+M1: Trial Vaccine		Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Saline: Sodium Chloride Placebo		Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.); MVA-NP+M1: Trial Vaccine Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml)		Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Saline: Sodium Chloride Placebo Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml)
All Cause Mortality
	MVA-NP+M1 (Vaccination Phase)		Saline Placebo (Vaccination Phase)		MVA-NP+M1 (Challenge Phase)		Saline Placebo (Challenge Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/87 (0%)		0/58 (0%)		0/71 (0%)		0/47 (0%)
Serious Adverse Events
	MVA-NP+M1 (Vaccination Phase)		Saline Placebo (Vaccination Phase)		MVA-NP+M1 (Challenge Phase)		Saline Placebo (Challenge Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/87 (1.1%)		0/58 (0%)		0/71 (0%)		1/47 (2.1%)
Pregnancy, puerperium and perinatal conditions
Foetal death	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Psychiatric disorders
Acute Psychosis	0/87 (0%)	0	0/58 (0%)	0	0/71 (0%)	0	1/47 (2.1%)	1
Other (Not Including Serious) Adverse Events
	MVA-NP+M1 (Vaccination Phase)		Saline Placebo (Vaccination Phase)		MVA-NP+M1 (Challenge Phase)		Saline Placebo (Challenge Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/87 (41.4%)		18/58 (31%)		30/71 (42.3%)		21/47 (44.7%)
Cardiac disorders
Atrial Flutter	0/87 (0%)	0	0/58 (0%)	0	0/71 (0%)	0	1/47 (2.1%)	1
Ear and labyrinth disorders
Ear Discomfort	0/87 (0%)	0	1/58 (1.7%)	1	2/71 (2.8%)	2	0/47 (0%)	0
Eye disorders
Lacrimation Increased	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Swelling of Eyelid	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Eye Irritation	0/87 (0%)	0	0/58 (0%)	0	2/71 (2.8%)	2	0/47 (0%)	0
Conjunctival Hyperaemia	0/87 (0%)	0	0/58 (0%)	0	0/71 (0%)	0	1/47 (2.1%)	1
Gastrointestinal disorders
Diarrhoea	5/87 (5.7%)	5	3/58 (5.2%)	3	3/71 (4.2%)	3	0/47 (0%)	0
Abdominal Discomfort	0/87 (0%)	0	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Abdominal Pain	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	2/47 (4.3%)	2
Abdominal Pain Upper	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Constipation	1/87 (1.1%)	1	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
Dry Mouth	0/87 (0%)	0	1/58 (1.7%)	1	0/71 (0%)	0	1/47 (2.1%)	1
Nausea	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	1/47 (2.1%)	1
Regurgitation	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
Toothache	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
Vomiting	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
General disorders
Inflammation	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Asthenia	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
Infections and infestations
Nasopharyngitis	6/87 (6.9%)	7	4/58 (6.9%)	4	0/71 (0%)	0	0/47 (0%)	0
Gastroenteritis	0/87 (0%)	0	2/58 (3.4%)	2	0/71 (0%)	0	0/47 (0%)	0
Oral Herpes	2/87 (2.3%)	2	0/58 (0%)	0	1/71 (1.4%)	1	1/47 (2.1%)	1
Conjunctivitis	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Rhinitis	0/87 (0%)	0	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Upper Respiratory Tract Infection	0/87 (0%)	0	0/58 (0%)	0	0/71 (0%)	0	1/47 (2.1%)	1
Injury, poisoning and procedural complications
Subcutaneous Haematoma	1/87 (1.1%)	1	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Arthropod Bite	0/87 (0%)	0	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Joint Injury	0/87 (0%)	0	1/58 (1.7%)	1	1/71 (1.4%)	1	0/47 (0%)	0
Ligament Sprain	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Limb injury	0/87 (0%)	0	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Skin Wound	0/87 (0%)	0	0/58 (0%)	0	0/71 (0%)	0	1/47 (2.1%)	1
Metabolism and nutrition disorders
Decreased Appetite	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	3/87 (3.4%)	4	0/58 (0%)	0	4/71 (5.6%)	4	6/47 (12.8%)	6
Neck Pain	2/87 (2.3%)	2	1/58 (1.7%)	1	0/71 (0%)	0	1/47 (2.1%)	1
Bursitis	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
Flank Pain	0/87 (0%)	0	0/58 (0%)	0	0/71 (0%)	0	1/47 (2.1%)	1
Musculoskeletal Pain	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
Musculoskeletal Stiffness	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
Nervous system disorders
Headache	5/87 (5.7%)	5	2/58 (3.4%)	2	2/71 (2.8%)	2	1/47 (2.1%)	1
Dizziness Postural	0/87 (0%)	0	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Presyncope	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	0/47 (0%)	0
Reproductive system and breast disorders
Dysmenorrhoea	1/87 (1.1%)	1	0/58 (0%)	0	2/71 (2.8%)	2	1/47 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Throat Irritation	3/87 (3.4%)	3	2/58 (3.4%)	2	0/71 (0%)	0	0/47 (0%)	0
Epistaxis	3/87 (3.4%)	3	0/58 (0%)	0	2/71 (2.8%)	2	0/47 (0%)	0
Rhinorrhoea	2/87 (2.3%)	2	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Sneezing	1/87 (1.1%)	1	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Cough	0/87 (0%)	0	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Dry Throat	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Nasal Congestion	0/87 (0%)	0	1/58 (1.7%)	1	0/71 (0%)	0	0/47 (0%)	0
Dysphonia	0/87 (0%)	0	0/58 (0%)	0	0/71 (0%)	0	1/47 (2.1%)	1
Skin and subcutaneous tissue disorders
Urticaria	3/87 (3.4%)	3	1/58 (1.7%)	1	2/71 (2.8%)	2	0/47 (0%)	0
Skin Irritation	2/87 (2.3%)	2	1/58 (1.7%)	1	3/71 (4.2%)	3	1/47 (2.1%)	1
Eczema	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0
Dry Skin	0/87 (0%)	0	0/58 (0%)	0	1/71 (1.4%)	1	1/47 (2.1%)	1
Surgical and medical procedures
Scar Excision	1/87 (1.1%)	1	0/58 (0%)	0	0/71 (0%)	0	0/47 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.