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Trial record 5 of 94820 for:    5

Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Healthy Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01776541
Recruitment Status : Completed
First Posted : January 28, 2013
Results First Posted : February 3, 2015
Last Update Posted : February 3, 2015
Sponsor:
Collaborator:
Department of Health and Human Services
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Pandemic H5N1 Influenza
Intervention Biological: Adjuvanted H5N1 pandemic influenza vaccine
Enrollment 979
Recruitment Details Subjects were enrolled at 4 centers in the US, 3 centers in Australia and 1 center in Thailand.
Pre-assignment Details All enrolled subjects were included in the trial.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.
Period Title: Overall Study
Started 488 491
Completed 432 416
Not Completed 56 75
Reason Not Completed
Administrative Reason             6             2
Death             4             0
Lost to Follow-up             27             48
Unclassified             5             4
Protocol Violation             2             1
Withdrawal by Subject             12             20
Arm/Group Title High Dose Low Dose Total
Hide Arm/Group Description Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart. Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart. Total of all reporting groups
Overall Number of Baseline Participants 488 491 979
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 488 participants 491 participants 979 participants
39.0  (13.7) 38.4  (14.2) 38.7  (14.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 488 participants 491 participants 979 participants
Female
285
  58.4%
259
  52.7%
544
  55.6%
Male
203
  41.6%
232
  47.3%
435
  44.4%
1.Primary Outcome
Title Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain.
Hide Description

The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion.

CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

Time Frame Three weeks after 2nd vaccination (day 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Full Analysis Set (FAS) i.e., the subjects who actually receive at least one dose of study vaccination and provide at least one evaluable serum sample both before (baseline) and after vaccination.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 478 483
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1
4
(3 to 6)
4
(2 to 6)
Day 43 (N=451,440)
85
(81 to 88)
63
(58 to 68)
2.Primary Outcome
Title Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.
Hide Description

Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion.

Seroconversion is defined as either a) in subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer.

CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.

Time Frame Three weeks after 2nd vaccination (day 43)
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was done on the FAS population.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 451 440
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
83
(79 to 86)
61
(56 to 66)
3.Primary Outcome
Title Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination.
Hide Description Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine.
Time Frame From day 1 through day 7 after any vaccination.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 473 471
Measure Type: Number
Unit of Measure: Number of subjects
Any Local 322 236
Injection site Erythema(N=471,471) 4 0
Injection site Induration(N=471,471) 54 35
Injection site Ecchymosis(N=472,471) 9 6
Injection site Pain(N=471,470) 318 235
Any Systemic 223 209
Nausea(N=472,471) 54 48
Myalgia(N=472,469) 108 78
Arthralgia(N=471,467) 70 52
Headache(N=471,469) 126 114
Fatigue(N=471,469) 125 108
Loss of Appetite(N=472,469) 53 38
Malaise(N=472,467) 117 97
Fever (≥38°C)(N=472,469) 11 9
Treatment of pain and (or) fever(N=471,470) 40 31
Prevention of pain and (or) fever(N=471,470) 7 14
Fever (≥40°C)(N=472,469) 1 0
4.Primary Outcome
Title Number of Subjects Reporting Unsolicited AEs After Any Vaccination.
Hide Description Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.
Time Frame Any unsolicited AEs - day 1 through day 22 after any vaccination. SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 476 475
Measure Type: Number
Unit of Measure: Number of subjects
Any AEs 94 92
At least possibly related AEs 39 31
Any SAEs 20 8
Deaths 4 0
Medically attended AEs 171 153
AEs resulting in premature withdrawal from study 4 0
AEs of Special Interest 1 0
AEs leading to New Onset of Chronic Disease 11 14
5.Secondary Outcome
Title Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine.
Hide Description

Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c is reported.

The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5 for subjects 18-60 years of age.

Time Frame Day 1; day 22; day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS set.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 464 461
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
Day22/Day1
5.37
(4.6 to 6.27)
2.43
(2.07 to 2.84)
Day43/Day1 (N=451,440)
41
(34 to 49)
11
(8.68 to 13)
Day387/Day1 (N=411,395)
1.95
(1.73 to 2.19)
1.24
(1.1 to 1.4)
6.Secondary Outcome
Title Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain.
Hide Description

Immunogenicity was assessed in terms of percentage of subjects achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion.

European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

Time Frame Day 1, day 22, day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS set.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 478 483
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1
4
(3 to 6)
4
(2 to 6)
Day 22 (N=464,461)
52
(47 to 56)
30
(26 to 35)
Day 43 (N=451,440)
85
(81 to 88)
63
(58 to 68)
Day 387 (N=411,395)
27
(22 to 31)
11
(8 to 15)
7.Secondary Outcome
Title Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.
Hide Description

Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion.

Seroconversion is defined as: a) for subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) for subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer.

The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.

Time Frame Day 22, day 43 and day 387
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the FAS set.
Arm/Group Title High Dose Low Dose
Hide Arm/Group Description:
Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart.
Overall Number of Participants Analyzed 464 461
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 22
48
(44 to 53)
27
(23 to 31)
Day 43 (N=451,440)
83
(71 to 91)
61
(45 to 75)
Day 387 (N=411,395)
22
(18 to 26)
9
(6 to 12)
Time Frame Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387.
Adverse Event Reporting Description

All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment.

Subjects who did not provide unsolicited safety data were excluded from safety evaluation.

 
Arm/Group Title High Dose Low Dose Total
Hide Arm/Group Description Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Total of high dose and low dose groups.
All-Cause Mortality
High Dose Low Dose Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
High Dose Low Dose Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   20/485 (4.12%)   8/490 (1.63%)   28/975 (2.87%) 
Cardiac disorders       
MYOCARDIAL INFARCTION * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
Gastrointestinal disorders       
PANCREATITIS * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
General disorders       
NON-CARDIAC CHEST PAIN * 1  0/485 (0.00%)  1/490 (0.20%)  1/975 (0.10%) 
Hepatobiliary disorders       
CHOLECYSTITIS * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
CHOLELITHIASIS * 1  1/485 (0.21%)  1/490 (0.20%)  2/975 (0.21%) 
JAUNDICE * 1  0/485 (0.00%)  1/490 (0.20%)  1/975 (0.10%) 
Infections and infestations       
APPENDICITIS * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
GASTROENTERITIS VIRAL * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
INFLUENZA * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
PNEUMONIA * 1  2/485 (0.41%)  0/490 (0.00%)  2/975 (0.21%) 
PYELONEPHRITIS * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
SEPSIS * 1  2/485 (0.41%)  0/490 (0.00%)  2/975 (0.21%) 
Injury, poisoning and procedural complications       
BRAIN CONTUSION * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
CONTUSION * 1  0/485 (0.00%)  1/490 (0.20%)  1/975 (0.10%) 
LIMB CRUSHING INJURY * 1  0/485 (0.00%)  1/490 (0.20%)  1/975 (0.10%) 
POST LAMINECTOMY SYNDROME * 1  0/485 (0.00%)  1/490 (0.20%)  1/975 (0.10%) 
POSTOPERATIVE ADHESION * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
ROAD TRAFFIC ACCIDENT * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
LARYNGEAL SQUAMOUS CELL CARCINOMA * 1  0/485 (0.00%)  1/490 (0.20%)  1/975 (0.10%) 
Nervous system disorders       
CEREBRAL HAEMORRHAGE * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
NERVE COMPRESSION * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
SUBARACHNOID HAEMORRHAGE * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
Pregnancy, puerperium and perinatal conditions       
ABORTION MISSED * 1  0/485 (0.00%)  1/490 (0.20%)  1/975 (0.10%) 
ABORTION SPONTANEOUS * 1  1/485 (0.21%)  1/490 (0.20%)  2/975 (0.21%) 
Renal and urinary disorders       
NEPHROLITHIASIS * 1  2/485 (0.41%)  0/490 (0.00%)  2/975 (0.21%) 
Respiratory, thoracic and mediastinal disorders       
ACUTE RESPIRATORY FAILURE * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
Vascular disorders       
RAYNAUD'S PHENOMENON * 1  1/485 (0.21%)  0/490 (0.00%)  1/975 (0.10%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
High Dose Low Dose Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   371/485 (76.49%)   324/490 (66.12%)   695/975 (71.28%) 
Gastrointestinal disorders       
NAUSEA  1  58/485 (11.96%)  51/490 (10.41%)  109/975 (11.18%) 
General disorders       
FATIGUE  1  125/485 (25.77%)  111/490 (22.65%)  236/975 (24.21%) 
INJECTION SITE ERYTHEMA  1  76/485 (15.67%)  61/490 (12.45%)  137/975 (14.05%) 
INJECTION SITE HAEMORRHAGE  1  42/485 (8.66%)  28/490 (5.71%)  70/975 (7.18%) 
INJECTION SITE INDURATION  1  59/485 (12.16%)  41/490 (8.37%)  100/975 (10.26%) 
INJECTION SITE PAIN  1  319/485 (65.77%)  244/490 (49.80%)  563/975 (57.74%) 
MALAISE  1  117/485 (24.12%)  97/490 (19.80%)  214/975 (21.95%) 
Infections and infestations       
UPPER RESPIRATORY TRACT INFECTION  1  53/485 (10.93%)  44/490 (8.98%)  97/975 (9.95%) 
Metabolism and nutrition disorders       
DECREASED APPETITE  1  56/485 (11.55%)  38/490 (7.76%)  94/975 (9.64%) 
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  75/485 (15.46%)  60/490 (12.24%)  135/975 (13.85%) 
MYALGIA  1  112/485 (23.09%)  82/490 (16.73%)  194/975 (19.90%) 
Nervous system disorders       
HEADACHE  1  134/485 (27.63%)  120/490 (24.49%)  255/975 (26.15%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Posting Director
Organization: Novartis Vaccines and Diagnostics
EMail: RegistryContactVaccinesUS@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT01776541     History of Changes
Other Study ID Numbers: V89_04
First Submitted: January 20, 2013
First Posted: January 28, 2013
Results First Submitted: January 20, 2015
Results First Posted: February 3, 2015
Last Update Posted: February 3, 2015