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CompletedNCT02680002Updated Aug 31, 2020Results posted

Assess the Safety & Immunogenicity of Stored Inactivated Influenza H5N1 Virus Vaccine Given With & Without Stored MF59 Adjuvant

A Phase 2 interventional study of 7.5 mcg H5N1 (stored as monobulk) and 15 mcg H5N1 (stored as monobulk) in A/Vietnam/H5N1 Influenza Virus, sponsored by Biomedical Advanced Research and Development Authority. Completed at 6 sites in United States. Open to participants aged 18 Years to 49 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-08-31.

Sponsored by Biomedical Advanced Research and Development Authority · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
422
Allocation
Randomized
Ages
18 Years to 49 Years
Sex
All
01

Study summary

The main purpose of this study is to assess the usability of long-term stored H5N1 antigen and adjuvant. The study is designed to assist in stockpile management by assessing the safety, reactogenicity, and immunogenicity long-term stored influenza A/Vietnam/H5N1 vaccine when administered with or without MF59® adjuvant.

Read the detailed description

This study is a randomized, double-blinded, Phase 2 study to assess the safety and immunogenicity of 2 doses of long-term stored inactivated monovalent influenza A/Vietnam/H5N1 virus vaccine administered intramuscularly with or without MF59 adjuvant in healthy males and nonpregnant females, aged 18 to 49 years, inclusive. This study is designed to assist in stockpile management and will assess the usability of long-term stored H5N1 antigen (ie, stored >10 years) and adjuvant (ie, stored >5 years).

02

Conditions studied

  • A/Vietnam/H5N1 Influenza Virus
03

Who can participate

Ages eligible
18 Years to 49 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Male or nonpregnant female
  • Provide written informed consent prior to study-related procedures
  • Stable health status
  • Access to consistent and reliable means of telephone contact
  • Able to understand and comply with planned study procedures
  • Agree to stay in contact with site, and no plans to move from study area for study duration

Exclusion criteria

Exclusion Criteria:

  • Allergic to eggs, other vaccine components, or squalene-based adjuvants
  • Women with positive pregnancy test within 24 hours of vaccination, or are breastfeeding
  • Females of childbearing potential who refuse acceptable birth control, if sexually active, have not used birth control for 2 months prior to study entry
  • Have immunosuppression or use anticancer chemotherapy or radiation therapy within preceding 36 months
  • Have an active neoplastic disease or history of hematologic malignancy
  • Have long term use (≥14 consecutive days) of glucocorticoids (>20 mg/day) or high-dose inhaled steroids (>800 mcg/day) within preceding 6 months
  • Diagnosis of schizophrenia, bipolar disease, or major psychiatric diagnosis
  • Have been hospitalized for psychiatric illness, attempted suicide or deemed danger to self or others within past 10 years
04

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
422 participants (actual)

Study arms

  • Experimental
    7.5 mcg H5N1 (monobulk) Plus MF59 (monobulk)

    Two 0.5-mL doses, given at Day 0 and 21 consisting of 7.5 mcg hemagglutinin (HA) antigen stored long-term as monobulk inactivated

    Biological: 7.5 mcg H5N1 (stored as monobulk) · Other: MF59 (stored as monobulk)

  • Experimental
    15 mcg H5N1 (monobulk) Plus MF59 (monobulk)

    Two 0.5-mL doses, given at Day 0 and 21 consisting of 15 mcg HA antigen stored long-term as monobulk inactivated A/Vietnam/H5N1 vaccine and MF59 stored long-term as monobulk MF59 adjuvant

    Biological: 15 mcg H5N1 (stored as monobulk) · Other: MF59 (stored as monobulk)

  • Experimental
    7.5 mcg H5N1 (monobulk) Plus MF59 (vials)

    Two 0.5-mL doses, given at Day 0 and 21 consisting of 7.5 mcg HA antigen stored long-term as monobulk inactivated A/Vietnam/H5N1 vaccine and MF59 stored short-term in vials as MF59 adjuvant

    Biological: 7.5 mcg H5N1 (stored as monobulk) · Other: MF59

  • Experimental
    15 mcg H5N1 (monobulk) Plus MF59 (vials)

    Two 0.5-mL doses, given at Day 0 and 21 consisting of 15 mcg HA antigen stored long-term as monobulk inactivated A/Vietnam/H5N1 vaccine and MF59 stored short-term in vials as MF59 adjuvant

    Biological: 15 mcg H5N1 (stored as monobulk) · Other: MF59

  • Experimental
    90 mcg H5N1 (monobulk) without MF59

    Two 1.0-mL doses at Day 0 and 21 consisting of 90 mcg HA antigen stored long-term as monobulk inactivated A/Vietnam/H5N1 antigen formulated and filled in 2015, administered without MF59

    Biological: 90 mcg H5N1 (stored as monobulk)

  • Experimental
    90 mcg H5N1 (vials) without MF59

    Two 1.0-mL doses at Day 0 and 21 consisting of 90 mcg HA antigen stored long-term in vials as inactivated A/Vietnam/H5N1 vaccine, administered without MF59

    Biological: 90 mcg H5N1 (stored in vials)

Interventions

  • Biological7.5 mcg H5N1 (stored as monobulk)
  • Biological15 mcg H5N1 (stored as monobulk)
  • Biological90 mcg H5N1 (stored as monobulk)
  • Biological90 mcg H5N1 (stored in vials)
  • OtherMF59
  • OtherMF59 (stored as monobulk)
05

What researchers measure

Primary outcomes

  1. Number of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.

    Occurence of mild, moderate, or severe solicited local symptoms during the 7 days (Days 0 to 7) following Dose 1

    Time frame: Days 0 to 7

  2. Number of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.

    Occurence of mild, moderate, or severe solicited local symptoms during the 7 days (Days 21 to 28) following Dose 2

    Time frame: Days 21 to 28

  3. Number of Participants With >=1 (More Than or Equal to 1) Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.

    Number of participants with \>=1 mild, moderate, or severe solicited local symptoms during the 7 days (Days 0 to 7) following Dose 1

    Time frame: Days 0 to 7

  4. Number of Participants With >=1 (More Than or Equal to 1) Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.

    Number of participants with \>=1 mild, moderate, or severe solicited local symptoms during the 7 days (Days 21 to 29) following Dose 2

    Time frame: Days 21 to 28

  5. Number of Participants With Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination.

    Number of participants with mild, moderate, or severe solicited systemic reactogenicity adverse events during the 7 days (Days 0 to 7) following Dose 1

    Time frame: Days 0 to 7

  6. Number of Participants With of Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination.

    Number of participants with of mild, moderate, or severe solicited systemic reactogenicity adverse events during the 7 days (Days 21 to 28) following Dose 2

    Time frame: Days 21 to 28

  7. Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody

    Geometric Mean Titer (GMT) of hemagglutination inhibition (HAI) antibody against A/Vietnam/H5N1 antigen in each study group

    Time frame: 21 days after receipt of second dose of vaccine (Day 42) (plus or minus 3 days)

Secondary outcomes

  1. Number of Participants With Vaccine-associated Serious Adverse Events (SAE) or Adverse Event of Special Interests (AESI)

    Number of participants with vaccine-associated serious adverse events (SAE) or adverse event of special interests (AESI) and occurence of AESIs or AEs leading to study withdrawal

    Time frame: First vaccination through 13 months

  2. Number of Participants With Adverse Events of Special Interest (AESI) or Adverse Events (AE) Leading to Study Withdrawal.

    Number of participants with adverse events of special interest (AESI) or adverse events (AE) leading to study withdrawal.

    Time frame: First vaccination through approximately 13 months after first vaccination

  3. Number of Participants With Unsolicited Adverse Events (AE)

    Number of participants with unsolicited adverse events (AE) through Visit 8 (Day 201)

    Time frame: Day 0 (Visit 1) through Day 201 (Visit 8)

  4. Frequency of Unsolicited Adverse Events (AE)

    Frequency of unsolicited adverse events (AE) for 21 days following Dose 1 (Days 0-21) and after Dose 2 (\>21 Days)

    Time frame: 21 days following each vaccination (Days 0-21, >21 Days)

  5. Occurrence of Clinical Safety Laboratory AEs

    Occurrence of clinical safety laboratory AEs at 7 and 21 days after each vaccination

    Time frame: 7 and 21 days after each vaccination (Days 0, 7, 21, 28, and 42)

  6. GMT (Geometric Mean Titers) of Serum HAI (Hemagglutination Inhibition) Antibodies

    Overall GMTs of HAI antibodies at baseline (Day 0) and Days 21, 28 and 201

    Time frame: Day 0 (Visit 1), Day 21 (Visit 4), Day 28 (Visit 6), Day 201 (Visit 8)

  7. GMT (Geometric Mean Titers) of Serum Microneutralization (MN) Antibodies

    GMT of serum MN antibodies at baseline (Day 0) and Days 21, 28, 42 and 201

    Time frame: Day 0 (Visit 1), Day 21 (Visit 4), Day 28 (Visit 6), Day 42 (Visit 7), Day 201 (Visit 8)

  8. Serum HAI (Hemagglutination Inhibition) Titer of at Least 1:40

    Proportion of participants achieving a serum HAI titer of at least 1:40 against the A/Vietnam/H5N1 antigen

    Time frame: Days 0 (Visit 1), 21 (Visit 4, +1day), 28 (Visit 6, +1 day), 42 (Visit 7, plus or minus 3 days), and 201 (Visit 8, plus or minus 7 days)

  9. Seroconversion Rate (SCR) for Hemagglutination Inhibition (HAI) Antibodies

    Defined as proportion of subjects achieving either a prevaccination HAI titer of \<1:10 and postvaccination titer of at least 1:40 or a prevaccination HAI titer of at least 1:10 and a 4-fold or greater increase of HAI postvaccination antibody titers against the A/Vietnam/H5N1 antigen; if baseline HAI titer is undetectable, it will be assigned a vaue of half the lower limit of detection.

    Time frame: Days 21, 28, 42, and 201

  10. Seroconversion Rate (SCR) for Microneutralization (MN) Antibodies

    Defined as proportion of subjects achieving either a prevaccination MN titer of \<1:10 and postvaccination titer of at least 1:40 or a prevaccination MN titer of at least 1:10 and a 4-fold or greater increase of MN postvaccination antibody titers against the A/Vietnam/H5N1 antigen; if baseline MN titer is undetectable, it will be assigned a vaue of half the lower limit of detection.

    Time frame: Days 21, 28, 42, and 201

06

Results

Posted Aug 31, 2020
Limitations and caveats
Protocol implied Clinical Study Report (CSR) would include Day 386 (end-of-study) data. Following start of study it was decided CSR would include data up to and including Day 201. CSR addendum will include data from Day 201-Day 386.

Participant flow

Participants were screened and enrolled at 6 sites in the US.

Participant flow — Overall Study
Milestone7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Started717070717070
Day 0 (dose 1)707070717068
Day 21 (dose 2)636865696563
Day 201586660675961
Completed586660675961
Not completed134104119
Withdrew: Lost to follow-up514202
Withdrew: Physician decision511111
Withdrew: Protocol violation101012
Withdrew: Withdrawal by subject001022
Withdrew: Missed visit 8 (day 201)213150
Withdrew: Other010010
Withdrew: Adverse event000012

Outcome measures

PrimaryNumber of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.

Occurence of mild, moderate, or severe solicited local symptoms during the 7 days (Days 0 to 7) following Dose 1

Time frame:
Days 0 to 7
Reported as:
Number · occurrences
Number of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.
occurrences7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Total number solicited local AEs (Adverse Events)344134342833
Total no. Mild solicited AEs313730292329
Total no. Moderate solicited AEs344354
Total no. Severe solicited AEs000200
PrimaryNumber of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.

Occurence of mild, moderate, or severe solicited local symptoms during the 7 days (Days 21 to 28) following Dose 2

Time frame:
Days 21 to 28
Reported as:
Number · occurrences
Number of Occurences of Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.
occurrences7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Total number solicited local AEs (Adverse Events)262423241823
Total no. Mild solicited AEs262223231721
Total no. Moderate solicited AEs020112
Total no. Severe solicited AEs000000
PrimaryNumber of Participants With >=1 (More Than or Equal to 1) Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.

Number of participants with \>=1 mild, moderate, or severe solicited local symptoms during the 7 days (Days 0 to 7) following Dose 1

Time frame:
Days 0 to 7
Reported as:
Count of participants · Participants
Number of Participants With >=1 (More Than or Equal to 1) Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.
Participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Total number solicited local AEs (Adverse Events)253127272225
Total no. Mild solicited local AEs232824241821
Total no. Moderate solicited local AEs233244
Total no. Severe solicited local AEs000100
PrimaryNumber of Participants With >=1 (More Than or Equal to 1) Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.

Number of participants with \>=1 mild, moderate, or severe solicited local symptoms during the 7 days (Days 21 to 29) following Dose 2

Time frame:
Days 21 to 28
Reported as:
Count of participants · Participants
Number of Participants With >=1 (More Than or Equal to 1) Mild, Moderate, or Severe Solicited Local Symptoms During the 7 Days After Each Vaccination.
Participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Total number solicited local AEs (Adverse Events)202017211721
Total no. Mild solicited local AEs201917201619
Total no. Moderate solicited local AEs010112
Total no. Severe solicited local AEs000000
PrimaryNumber of Participants With Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination.

Number of participants with mild, moderate, or severe solicited systemic reactogenicity adverse events during the 7 days (Days 0 to 7) following Dose 1

Time frame:
Days 0 to 7
Reported as:
Number · participants
Number of Participants With Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination.
participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Total no. solicited systemic AEs (Adverse Events)20 (18.4 to 40.6)17 (14.8 to 36.0)23 (22.1 to 45.1)24 (23.0 to 46.0)17 (14.8 to 36.0)18 (16.5 to 38.6)
Total no. Mild solicited systemic AEs13 (10.3 to 29.7)14 (11.4 to 31.3)17 (14.8 to 36.0)19 (16.9 to 38.6)13 (10.3 to 29.7)13 (10.6 to 30.5)
Total no. Moderate solicited systemic AEs7 (4.1 to 19.5)3 (0.9 to 12.0)6 (3.2 to 17.7)4 (1.6 to 13.8)4 (1.6 to 14.0)3 (0.9 to 12.4)
Total no. Severe solicited systemic AEs0 (0.0 to 5.1)0 (0.0 to 5.1)0 (0.0 to 5.1)1 (0.0 to 7.6)0 (0.0 to 5.1)2 (0.4 to 10.2)
PrimaryNumber of Participants With of Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination.

Number of participants with of mild, moderate, or severe solicited systemic reactogenicity adverse events during the 7 days (Days 21 to 28) following Dose 2

Time frame:
Days 21 to 28
Reported as:
Number · participants
Number of Participants With of Mild, Moderate, or Severe Solicited Systemic Reactogenicity Symptoms During the 7 Days After Each Vaccination.
participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Total no. solicited systemic AEs (Adverse Events)11 (9.1 to 29.1)10 (7.3 to 25.4)11 (8.8 to 28.3)17 (15.1 to 36.5)9 (6.5 to 24.7)9 (6.7 to 25.4)
Total no. Mild solicited systemic AEs8 (5.6 to 23.5)10 (7.3 to 25.4)10 (7.6 to 26.5)11 (8.2 to 26.7)5 (2.5 to 17.0)9 (6.7 to 25.4)
Total no. Moderate solicited systemic AEs3 (1.0 to 13.3)0 (0.0 to 5.3)1 (0.0 to 8.3)6 (3.3 to 18.0)4 (1.7 to 15.0)0 (0.0 to 5.7)
Total no. Severe solicited systemic AEs0 (0.0 to 5.7)0 (0.0 to 5.7)0 (0.0 to 5.5)0 (0.0 to 5.2)0 (0.0 to 5.5)0 (0.0 to 5.7)
PrimaryGeometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody

Geometric Mean Titer (GMT) of hemagglutination inhibition (HAI) antibody against A/Vietnam/H5N1 antigen in each study group

Time frame:
21 days after receipt of second dose of vaccine (Day 42) (plus or minus 3 days)
Reported as:
Geometric mean · antibody titers
Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody
antibody titers7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody38 (28.7 to 50.4)29.6 (22.6 to 38.9)37.4 (28.3 to 49.4)49.4 (37.7 to 64.8)19.4 (14.6 to 25.7)19.9 (13.9 to 28.4)
PrimaryGeometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody

Geometric Mean Titer (GMT) of hemagglutination inhibition (HAI) antibody against A/Vietnam/H5N1 antigen in each study group

Time frame:
21 days after receipt of second dose of vaccine (Day 42) (plus or minus 3 days)
Reported as:
Median · antibody titers
Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody
antibody titers7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibody40.0 (5 to 320)40.0 (5 to 226)40.0 (5 to 453)56.6 (5 to 640)20 (5 to 640)14.1 (5 to 905)
SecondaryNumber of Participants With Vaccine-associated Serious Adverse Events (SAE) or Adverse Event of Special Interests (AESI)

Number of participants with vaccine-associated serious adverse events (SAE) or adverse event of special interests (AESI) and occurence of AESIs or AEs leading to study withdrawal

Time frame:
First vaccination through 13 months
Reported as:
Count of participants · Participants
Number of Participants With Vaccine-associated Serious Adverse Events (SAE) or Adverse Event of Special Interests (AESI)
Participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Vaccine-associated Serious Adverse Event (SAE)000000
Adverse Event of Special Interest (AESI)000000
SecondaryNumber of Participants With Adverse Events of Special Interest (AESI) or Adverse Events (AE) Leading to Study Withdrawal.

Number of participants with adverse events of special interest (AESI) or adverse events (AE) leading to study withdrawal.

Time frame:
First vaccination through approximately 13 months after first vaccination
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events of Special Interest (AESI) or Adverse Events (AE) Leading to Study Withdrawal.
Participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Adverse Event of Special Interest (AESI)000000
Adverse Events (AE) leading to study withdrawal000012
SecondaryNumber of Participants With Unsolicited Adverse Events (AE)

Number of participants with unsolicited adverse events (AE) through Visit 8 (Day 201)

Time frame:
Day 0 (Visit 1) through Day 201 (Visit 8)
Reported as:
Count of participants · Participants
Number of Participants With Unsolicited Adverse Events (AE)
Participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Any unsolicited Adverse Event (AE)283736423127
Any severe unsolicited Adverse Event (AE)123233
SecondaryFrequency of Unsolicited Adverse Events (AE)

Frequency of unsolicited adverse events (AE) for 21 days following Dose 1 (Days 0-21) and after Dose 2 (\>21 Days)

Time frame:
21 days following each vaccination (Days 0-21, >21 Days)
Reported as:
Number · Unsolicited Adverse Events (AE)
Frequency of Unsolicited Adverse Events (AE)
Unsolicited Adverse Events (AE)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Days 0-21184179186202156174
>21 Days014214
SecondaryOccurrence of Clinical Safety Laboratory AEs

Occurrence of clinical safety laboratory AEs at 7 and 21 days after each vaccination

Time frame:
7 and 21 days after each vaccination (Days 0, 7, 21, 28, and 42)
Reported as:
Number · Clinical safety lab results reported
Occurrence of Clinical Safety Laboratory AEs
Clinical safety lab results reported7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Visit 1: Day 0010000
Visit 3: Day 7010001
Visit 4: Day 21010000
Visit 6: Day 28010000
Visit 7: Day 42010000
SecondaryGMT (Geometric Mean Titers) of Serum HAI (Hemagglutination Inhibition) Antibodies

Overall GMTs of HAI antibodies at baseline (Day 0) and Days 21, 28 and 201

Time frame:
Day 0 (Visit 1), Day 21 (Visit 4), Day 28 (Visit 6), Day 201 (Visit 8)
Reported as:
Geometric mean · antibody titers
GMT (Geometric Mean Titers) of Serum HAI (Hemagglutination Inhibition) Antibodies
antibody titers7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Visit 1: Day 05.0 (5.0 to 5.1)5.0 (5.0 to 5.1)5.4 (5.0 to 5.8)5.2 (4.9 to 5.6)5.1 (5.0 to 5.2)5.3 (4.9 to 5.8)
Visit 4: Day 21 (+1 day)11.8 (9.0 to 15.4)8.6 (7.0 to 10.4)8.7 (6.7 to 11.4)14.8 (11.1 to 19.7)10.8 (8.0 to 14.6)14.1 (9.6 to 20.9)
Visit 6: Day 28 (+1 day)18.4 (13.8 to 24.5)18.7 (14.0 to 25.0)17.5 (13.2 to 23.2)27.9 (20.5 to 37.9)14.0 (10.3 to 19.1)20.7 (14.3 to 30.0)
Visit 8: Day 201 (plus or minus 7 days)6.2 (5.3 to 7.2)5.4 (5.1 to 5.7)5.5 (5.0 to 5.9)5.4 (5.1 to 5.8)5.9 (5.1 to 6.8)6.9 (5.6 to 8.6)
SecondaryGMT (Geometric Mean Titers) of Serum Microneutralization (MN) Antibodies

GMT of serum MN antibodies at baseline (Day 0) and Days 21, 28, 42 and 201

Time frame:
Day 0 (Visit 1), Day 21 (Visit 4), Day 28 (Visit 6), Day 42 (Visit 7), Day 201 (Visit 8)
Reported as:
Geometric mean · antibody titers
GMT (Geometric Mean Titers) of Serum Microneutralization (MN) Antibodies
antibody titers7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Visit 1: Day 06.1 (5.6 to 6.6)5.5 (5.2 to 5.8)5.5 (5.2 to 5.7)6.0 (5.6 to 6.5)5.4 (5.1 to 5.7)5.7 (5.4 to 6.1)
Visit 4: Day 21 (+1 day)12.2 (9.3 to 16.1)8.0 (6.9 to 9.3)10.9 (8.4 to 14.1)14.2 (11.0 to 18.4)10.7 (8.2 to 13.8)15.4 (10.5 to 22.6)
Visit 6: Day 28 (+1 day)24.0 (18.6 to 31.0)23.8 (19.1 to 29.7)24.9 (19.6 to 31.6)31.1 (24.1 to 40.2)16.8 (13.2 to 21.3)24.0 (16.9 to 34.1)
Visit 7: Day 42 (plus or minus 3 days)52.2 (39.2 to 69.7)43.0 (33.8 to 54.7)58.8 (45.4 to 76.1)66.4 (52.3 to 84.3)25.0 (20.2 to 31.0)30.1 (22.0 to 41.3)
Visit 8: Day 201 (plus or minus 7 days)11.3 (9.1 to 14.0)8.8 (7.5 to 10.1)10.9 (8.7 to 13.5)9.9 (8.3 to 11.7)8.9 (7.3 to 10.8)11.0 (8.0 to 15.0)
SecondarySerum HAI (Hemagglutination Inhibition) Titer of at Least 1:40

Proportion of participants achieving a serum HAI titer of at least 1:40 against the A/Vietnam/H5N1 antigen

Time frame:
Days 0 (Visit 1), 21 (Visit 4, +1day), 28 (Visit 6, +1 day), 42 (Visit 7, plus or minus 3 days), and 201 (Visit 8, plus or minus 7 days)
Reported as:
Count of participants · Participants
Serum HAI (Hemagglutination Inhibition) Titer of at Least 1:40
Participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Day 0 (Visit 1)001101
Day 21 (Visit 4, +1 day)1369181216
Day 28 (Visit 6, +1 day)222518331922
Day 42 (Visit 7, plus or minus 3 days)393842492122
Day 201 (Visit 8, plus or minus 7 days)101113
SecondarySeroconversion Rate (SCR) for Hemagglutination Inhibition (HAI) Antibodies

Defined as proportion of subjects achieving either a prevaccination HAI titer of \<1:10 and postvaccination titer of at least 1:40 or a prevaccination HAI titer of at least 1:10 and a 4-fold or greater increase of HAI postvaccination antibody titers against the A/Vietnam/H5N1 antigen; if baseline HAI titer is undetectable, it will be assigned a vaue of half the lower limit of detection.

Time frame:
Days 21, 28, 42, and 201
Reported as:
Count of participants · Participants
Seroconversion Rate (SCR) for Hemagglutination Inhibition (HAI) Antibodies
Participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Visit 4: Day 21 (+1 day)1368181216
Visit 6: Day 28 (+1day)222517331921
Visit 7: Day 42 (plus or minus 3 days)393841492121
Visit 8: Day 201 (plus or minus 7 days)101113
SecondarySeroconversion Rate (SCR) for Microneutralization (MN) Antibodies

Defined as proportion of subjects achieving either a prevaccination MN titer of \<1:10 and postvaccination titer of at least 1:40 or a prevaccination MN titer of at least 1:10 and a 4-fold or greater increase of MN postvaccination antibody titers against the A/Vietnam/H5N1 antigen; if baseline MN titer is undetectable, it will be assigned a vaue of half the lower limit of detection.

Time frame:
Days 21, 28, 42, and 201
Reported as:
Count of participants · Participants
Seroconversion Rate (SCR) for Microneutralization (MN) Antibodies
Participants7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Visit 4: Day 21 (+1 day)1031113912
Visit 6: Day 28 (+1day)182123311520
Visit 7: Day 42 (plus or minus 3 days)424344522323
Visit 8: Day 201 (plus or minus 7 days)518347

Adverse events

Collected over Adverse Event (AE) data were collected from Visit 1 (Day 0) through Visit 7 (Day 42); Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) were assessed from Visit 1 (Day 0), until exit from the study, Visit 9 (Day 386). Data currently available to Visit 8 (Day 201).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)0/70 (0%)0/70 (0%)44/70 (62.9%)
15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)0/71 (0%)1/71 (1.4%)49/71 (69%)
7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)0/70 (0%)3/70 (4.3%)47/70 (67.1%)
15 mcg H5N1 (Monobulk) Plus MF59 (Vials)0/71 (0%)0/71 (0%)57/71 (80.3%)
90 mcg H5N1 (Monobulk) Without MF590/70 (0%)1/70 (1.4%)48/70 (68.6%)
90 mcg H5N1 (Vials) Without MF590/69 (0%)2/69 (2.9%)47/69 (68.1%)
Most frequent serious events
Showing 10 of 15
Most frequent serious events
Event7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Abdominal painInjury, poisoning and procedural complications0/700/710/700/710/701/69
Gastrointestinal organ contusionInjury, poisoning and procedural complications0/700/710/700/710/701/69
Rib fractureInjury, poisoning and procedural complications0/700/710/700/710/701/69
Flank painInjury, poisoning and procedural complications0/700/710/700/710/701/69
Acute myocardial infarctionVascular disorders0/700/710/700/710/701/69
Organ failureGeneral disorders0/700/710/700/710/701/69
Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders0/700/710/700/710/701/69
Joint dislocationMusculoskeletal and connective tissue disorders0/700/711/700/710/700/69
Infected skin ulcerSkin and subcutaneous tissue disorders0/700/711/700/710/700/69
CellulitisInfections and infestations0/700/711/700/710/700/69
Most frequent other events
Most frequent other events
Event7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59
Injection site painGeneral disorders30/7033/7129/7033/7125/7029/69
HeadacheNervous system disorders17/7015/7115/7022/7113/7017/69
FatigueGeneral disorders14/7014/7112/7014/7111/7012/69
MyalgiaMusculoskeletal and connective tissue disorders7/7012/7111/7013/717/707/69
DiarrheaGastrointestinal disorders7/705/719/707/716/7011/69
Injection site indurationGeneral disorders8/709/717/704/714/708/69
NauseaGastrointestinal disorders6/704/715/709/712/703/69
Injection site erythemaGeneral disorders6/705/715/703/716/707/69
ArthralgiaMusculoskeletal and connective tissue disorders4/704/717/705/717/703/69

Baseline characteristics

Safety Population: Number of participants receiving at least one dose (Dose 1/Day 0) of the investigational product.

Age, Customized
Age, Customized(participants)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59Total
18 to <3016181117211598
30 to <40222126282231150
40 to 49323133262722171
Age, Customized
Age, Customized(years)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59Total
Mean36.7 ± 8.0236.8 ± 8.4738.1 ± 8.3735.7 ± 8.2534.9 ± 8.6236.0 ± 7.6036.4 ± 8.24
Age, Customized
Age, Customized(years)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59Total
Median38.0 (21 to 49)37.5 (20 to 48)38.5 (18 to 49)37.0 (18 to 48)37.0 (18 to 49)35.0 (18 to 49)37 (18 to 49)
Sex: Female, Male
Sex: Female, Male(Participants)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59Total
Female435033434139249
Male272037282929170
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59Total
White435250475146289
Black or African American271418221718116
Asian0110013
American Indian or Alaska Native0001203
Multiracial0210014
Other0101024
Region of Enrollment
Region of Enrollment(participants)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59Total
United States707070717068419
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m2)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59Total
Mean32.79 ± 9.2930.76 ± 8.5931.75 ± 8.3530.50 ± 8.1531.76 ± 8.1331.57 ± 9.2731.52 ± 8.62
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m2)7.5 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)15 mcg H5N1 (Monobulk) Plus MF59 (Monobulk)7.5 mcg H5N1 (Monobulk) Plus MF59 (Vials)15 mcg H5N1 (Monobulk) Plus MF59 (Vials)90 mcg H5N1 (Monobulk) Without MF5990 mcg H5N1 (Vials) Without MF59Total
Median30.93 (20.23 to 63.66)28.95 (17.76 to 61.42)29.79 (17.50 to 56.96)28.08 (13.89 to 53.45)30.21 (20.33 to 54.13)30.84 (17.89 to 71.43)29.70 (17.50 to 71.43)
07

Study locations

6 sites
  • Radiant Research, Inc.
    Atlanta, Georgia 30328, United States
  • Clinical Research Advantage, Inc./Ridge Family Practice
    Council Bluffs, Iowa 51503, United States
  • Johnson County Clin-Trials, Inc.
    Lenexa, Kansas 66219, United States
  • Central Kentucky Researcch Associates, Inc.
    Lexington, Kentucky 40509, United States
  • Radiant Research, Inc.
    Edina, Minnesota 55435, United States
  • Rochester Clinical Research, Inc.
    Rochester, New York 14609, United States
08

References and documents

Publications

  • Oshansky CM, Zhou J, Gao Y, Schweinle JE, Biscardi K, DeBeauchamp J, Pavetto C, Wollish A; BRITE Study Coordination Team; Webby RJ, Cioce V, Donis RO, Bright RA. Safety and immunogenicity of influenza A(H5N1) vaccine stored up to twelve years in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS). Vaccine. 2019 Jan 14;37(3):435-443. doi: 10.1016/j.vaccine.2018.11.069. Epub 2018 Dec 12. PubMed 30553570 ↗

Individual participant data

Plan to share: Yes — The study results will be posted on publicly available clinical trial registers.

09

Registry details

Key details

Study ID
NCT02680002
Lead sponsor
Biomedical Advanced Research and Development Authority
Collaborators
PPD DEVELOPMENT, LP
Responsible party
Sponsor
First posted
Feb 11, 2016
Start date
Mar 2016
Primary completion
May 13, 2016
Completion
Mar 31, 2017
Results posted
Aug 31, 2020
Last update
Aug 31, 2020

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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