A Phase I Study Priming With an Inactivated A/H7N9 Influenza Virus Vaccine With or Without MF59 Adjuvant Followed by Live Attenuated A/H7N9 Influenza Virus Vaccine

NCT02251288 | Completed Phase 1 FDA Drug

• 1 other identifier: 13-0087
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

A phase I prospective, randomized study in healthy adult subjects at a single center. Adult subjects age 18 to 47 years and meeting all enrollment criteria will choose to participate as subjects who receive inactivated vaccine followed by a live vaccine boost at 4 weeks (Group 1), 12 weeks (Group 2), or 24 weeks (Group 3), or to be in an observational group (Group 4) which will not be scheduled for a booster dose but may serve as a roll-over group for subjects who withdraw prior to the second vaccination but agree to remain in follow-up. A fifth group will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four weeks. The primary objectives of this study are to (1) assess the safety of H7N9 pLAIV administered to individuals who have previously received MF59-adjuvanted or unadjuvanted H7N9 pIIV, (2) evaluate the ability of a single dose of unadjuvanted H7N9 pIIV to prime for enhanced immunogenicity (booster response) to subsequent administration of antigenically-matched H7N9 pLAIV vaccine, and to (3) evaluate the ability of a single dose of MF59-adjuvanted H7N9 pIIV to prime for enhanced immunogenicity (booster response) to subsequent administration of antigenically-matched H7N9 pLAIV vaccine.

Conditions

Avian Influenza; Immunisation

Keywords

H7N9 pandemic; inactivated influenza vaccine (pIIV); live attenuated influenza vaccine (pLAIV); MF59 adjuvant

Outcome Measures

Primary Outcomes (35)

• Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA)

  Day 29

• Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Group 2

  Day 113

• Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Group 3

  Day 197

• Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) for Groups 1, 5

  Day 57

• Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 1

  Day 29 through Day 39

• Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 2

  Day 85 through Day 95

• Occurrence of respiratory reactogenicity following pLAIV vaccination for Group 3

  Day 169 through Day 179

• Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 1

  Day 29 through Day 39

• Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 2

  Day 85 through Day 95

• Occurrence of solicited systemic reactogenicity following pLAIV vaccination for Group 3

  Day 169 through Day 179

• Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 1

  Day 29 through Day 209

• Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 2

  Day 85 through Day 265

• Occurrence of study vaccine-related serious adverse events following pLAIV vaccination for Group 3

  Day 169 through Day 349

• Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 1

  Day 29 through Day 57

• Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 2

  Day 85 through 113

• Occurrence of study vaccine-related unsolicited non-serious adverse events following pLAIV vaccination for Group 3

  Day 169 through 197

• Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 2

  Day 113

• Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Group 3

  Day 197

• Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines for Groups 1, 5

  Day 57

• Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Group 2

  Day 113

• Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Group 3

  Day 197

• Percentage of subjects achieving seroconversion (a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer = / > 1:40 or a pre-vaccination HAI titer = / > 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) for Groups 1,5

  Day 57

• Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 1

  Day 29 through Day 36

• Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 2

  Day 85 through Day 92

• Percentage of subjects shedding vaccine virus as detected by rRT-PCR following pLAIV vaccination for Group 3

  Day 169 through Day 176

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells

  Day 29

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2

  Day 113

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2

  Day 141

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 2

  Day 265

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3

  Day 197

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3

  Day 225

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Group 3

  Day 349

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5

  Day 209

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5

  Day 57

• Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells for Groups 1, 5

  Day 85

Secondary Outcomes (72)

• Geometric mean titers of serum HAI antibody

  Day 1

• Geometric mean titers of serum HAI antibody

  Day 29

• Geometric mean titers of serum HAI antibody for Group 2

  Day 113

• Geometric mean titers of serum HAI antibody for Group 2

  Day 141

• Geometric mean titers of serum HAI antibody for Group 2

  Day 265

Study Arms (5)

Group 1

EXPERIMENTAL

12 patients receive Intramuscular (IM) A/H7N9 15 mcg on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of Intranasal (IN) sprayer 10\^7 FFU H7 N9 pLAIV on Day 29

Biological: Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca; Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59 adjuvant

Group 2

EXPERIMENTAL

12 patients receive A/H7N9 15 mcg IM on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of IN sprayer10\^7 FFU H7 N9 pLAIV on Day 85

Biological: Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca; Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59 adjuvant

Group 3

EXPERIMENTAL

12 patients receive S A/H7N9 15 mcg IM on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of IN sprayer 10\^7 FFU H7 N9 pLAIV on Day 169

Biological: Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca; Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59 adjuvant

Group 4

EXPERIMENTAL

8 patients receive A/H7N9 15 mcg IM on Day 1, 8 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59 adjuvant

Group 5

EXPERIMENTAL

12 patients receive A/H7N9 15 mcg plus MF59 adjuvant on Day 1 and Day 29

Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013; Drug: MF59 adjuvant

Interventions

Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca BIOLOGICAL

MedImmune supplies pLAIV vaccines as a colorless to pale yellow and clear to slightly cloudy suspension in single, unit-dose, Becton-Dickinson Accuspray™ Nasal Spray Systems sprayer devices. Each filled sprayer device contains a 0.5 mL dose of 10\^7FFU of H7N9 Anhui 2013/AA ca vaccine. Group I receives the IN dose on Day 29, Group 2 on Day 85, and Group 3 on Day 169.

Group 1; Group 2; Group 3

Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013 BIOLOGICAL

Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1

Group 1; Group 2; Group 3; Group 4; Group 5

MF59 adjuvant DRUG

Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.

Group 1; Group 2; Group 3; Group 4; Group 5

Eligibility Criteria

• Age: 18 Years - 47 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to initiation of any study procedures, including future use of specimens.
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Are males or non-pregnant, non-breastfeeding females, 18 to 47 years old, inclusive.

You may not qualify if:

• Oral temperature is less than 100.4 degrees Fahrenheit.
• Pulse is 55 to 100 bpm, inclusive.
• Systolic blood pressure is 90 to 140 mmHg, inclusive.
• Diastolic blood pressure is 55 to 90 mmHg, inclusive.
• Women of childbearing potential\* in sexual relationships with men must use an acceptable method of contraception\*\* from 30 days prior to pIIV administration until 90 days after last study vaccination.
• \*Not sterilized via tubal ligation, bilateral oophorectomy or hysterectomy and still menstruating or \< 1 year of the last menses if menopausal).
• \*\*Includes, but is not limited to, abstinence from intercourse with a male partner, monogamous relationship with a vasectomized partner, male condoms with the use of applied spermicide, intrauterine devices, and licensed hormonal methods, with use of a highly effective method of contraception for a minimum of 30 days prior to study product exposure and agree to practice highly effective contraception for the duration of study product exposure, including 3 months (defined as 90 days) after the last study vaccination. A highly effective method of contraception is defined as one which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.
• Have an acute illness within 72 hours prior to study vaccination.
• Any medical disease or condition that, in the opinion of the investigator, is a contraindication to study participation\*.
• \*Includes medical disease or condition that would place the subject at an unacceptable risk of injury, render them unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or their successful completion of the study.
• Have history of any significant acute or chronic medical conditions\* or need for chronic medications that, in the opinion of the investigator, will interfere with immunogenicity or affect safety.
• \*Chronic medical condition - a medical condition persisting 3 months (defined as 90 days) or longer
• Have immunosuppression or are taking systemic immunosuppressants as a result of an underlying illness or treatment.
• Diagnosis of asthma or reactive airway disease within the past 2 years.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Rochester Medical Center - Vaccine Research Unit

Rochester, New York, 14642-0001, United States

Location

MeSH Terms

Conditions

Influenza in Birds

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Bird Diseases; Animal Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2014
• First Posted: September 29, 2014
• Study Start: May 18, 2015
• Primary Completion: August 17, 2018
• Study Completion: August 17, 2018
• Last Updated: January 27, 2020

Record last verified: 2018-07-01

Locations

US (1)