Clinical trial NCT03283319: Panblok H7 Vaccine Adjuvanted With AS03 or MF59
Official title: Randomized, Double-Blinded, Phase 2 Study to Assess Safety and Immunogenicity of Panblok H7 Vaccine at Three Antigen Dose Levels Adjuvanted With AS03® or MF59®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza, Human
Keywords: Influenza
human
Influenza in Birds
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
MF59
AS03
Adjuvants
Immunologic
Lead sponsor: Biomedical Advanced Research and Development Authority
Sponsor class: FED
Collaborators: name: Rho, Inc.
First posted: 2017-09-14
Enrollment: 366
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to one of the six treatment groups at Day 1 and will receive the assigned dose of antigen and adjuvant on Day 1 and Day 29.
Primary purpose: PREVENTION

Brief summary: The main purpose of this study is to assess the safety and ability of a Panblok H7 influenza vaccine adjuvanted with AS03 or MF59 to generate an immune response after 2 doses separated by 28 days. Three different antigen dose levels of Panblok H7 will be tested.

Detailed description: This is a randomized, double-blinded, phase 2 study to assess safety and immunogenicity of Panblok H7 vaccine at three antigen dose levels (3.75, 7.5, and 15 μg) adjuvanted with AS03 or MF59. The main purpose of this study is to assess the safety and ability of the recombinant Panblok H7 influenza vaccine adjuvanted with AS03 or MF59 to generate an immune response after 2 doses separated by 28 days in healthy males and nonpregnant females, aged 18 to 49 years, inclusive. The expected study duration is approximately 13.5 months per participant.

Eligibility criteria: Inclusion Criteria:

1. Male or nonpregnant female 18 to 49 years of age, inclusive, at the time of the first study vaccination.
2. Provide written informed consent prior to the initiation of any study-related procedures.
3. Are able to understand and comply with planned study procedures.
4. Have a stable health status based on site investigator's clinical judgment, as established by physical examination, vital signs, and medical history.
5. Have access to a consistent and reliable means of telephone contact, which may be in the home, workplace, or by personal mobile electronic device.
6. Agree to stay in contact with the study site for the duration of the study, have no current plans to move from the study area, and agree to provide updated contact information as necessary.

Exclusion Criteria:

1. Have had a prior severe reaction to any influenza vaccine or have a known allergy to squalene-based adjuvants.
2. Women who are pregnant or breast feeding. Women of childbearing potential must have a negative urine pregnancy test at screening and within 24 hours prior to each vaccination.

   Women of childbearing potential are defined as postmenarcheal and premenopausal females capable of becoming pregnant. This does not include females who meet any of the following conditions: menopausal \>12 months, tubal ligation \>12 months, bilateral salpingo-oophorectomy, or hysterectomy.
3. Women of childbearing potential who refuse to use an acceptable method of birth control from screening to Day 50 (Visit 7) or, if sexually active with a male partner, who have not used a reliable birth control method during the 2 months prior to screening.

   Adequate contraception is defined as a contraceptive method with a failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label, for example: abstinence from penile-vaginal intercourse; oral contraceptives, either combined or progestogen alone; injectable progestogen; implants of etonogestrel or levonorgestrel; estrogenic vaginal ring; percutaneous contraceptive patches; intrauterine device or intrauterine system; male partner sterilization at least 6 months prior to the female participant's Screening Visit, and this male is the sole partner for that participant (the information on the male partner's sterility can come from the site personnel's review of the participant medical records or interview with the participant on her medical history); male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).
4. Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months, or plans to receive immunosuppressive therapy/cytotoxic treatment during study participation.
5. Have an active neoplastic disease or a history of any hematologic malignancy. However, participants with superficial skin cancer who do not require intervention other than local excision are not excluded.
6. Have long-term use (≥14 consecutive days) of glucocorticoids including oral or parenteral prednisone or prednisone equivalent (\>20 mg total dose per day) or high-dose inhaled steroids (\>800 µg/day of beclomethasone dipropionate or equivalent) within 1 month prior to screening in this study. However, participants on low-dose inhaled steroids (≤800 µg/day of beclomethasone dipropionate or equivalent) or topical steroids are not excluded.
7. History of schizophrenia, bipolar disease, psychosis, or severe personality disorder.
8. History of hospitalization for psychiatric illness, attempted suicide, or having been deemed a danger to self or others within the past 10 years.
9. Have received immunoglobulin or other blood product (with the exception of Rho\[D\] immune globulin) within the 3 months prior to screening in this study.
10. Have received any live vaccines within 4 weeks or inactivated or recombinant protein vaccines within 2 weeks prior to screening in this study or plan to receive such vaccines (including seasonal influenza vaccines) from screening through 21 days following the second dose of the study vaccine (Screening Visit through Day 50).
11. Have an acute or chronic medical condition that, in the opinion of the site investigator, would render vaccination unsafe or would interfere with the evaluation of responses. This includes all PIMMCs such as Guillain Barré syndrome, narcolepsy, and current or history of autoimmune or chronic inflammatory disease.
12. Have an acute illness, including body temperature greater than 100.4°F, at screening, immediately prior to each vaccination or, per participant report, within 3 days prior to each vaccination in this study.
13. Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to screening in this study or expect to receive an experimental agent during the study period.
14. Are participating or plan to participate in another interventional clinical trial (either active or follow up phase) during the study period.
15. Participated in an A(H7) influenza vaccine study in the past or have a history of A(H7) influenza infection prior to vaccination in this study.
16. Have known human immunodeficiency virus, hepatitis B, or hepatitis C infection (based on medical history).
17. Have a history of alcohol or drug abuse in the last 5 years.
18. Have a body mass index \>35 kg/m2.
19. Have a first degree relative with narcolepsy.
20. Have any laboratory test result or clinical findings (including vital signs) that singly or in combination are likely to unfavorably alter the risk-benefit of participation or to confound study safety or immunogenicity results. participants cannot be rescreened based on abnormal laboratory test results.
21. Alanine aminotransferase (AST) \>2 times the upper limit of normal (ULN), or bilirubin \>1.5 times the ULN unless isolated Gilbert's syndrome. participants cannot be rescreened based on abnormal laboratory test results.

Primary outcomes:
measure: Solicited Local Reactogenicity Symptoms for Participants Given Adjuvant AS03
timeFrame: Day 1-8, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
measure: Solicited Systemic Reactogenicity Symptoms for Participants Given Adjuvant AS03
timeFrame: Day 1-8, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
measure: Solicited Local Reactogenicity Symptoms for Participants Given Adjuvant MF59
timeFrame: Day 1-8, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
measure: Solicited Systemic Reactogenicity Symptoms for Participants Given Adjuvant MF59
timeFrame: Day 1-8, Day 29-36 (within 8 days of each vaccination, inclusive of the vaccination day)
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant AS03
timeFrame: Day 50
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant MF59
timeFrame: Day 50
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant AS03
timeFrame: Day 50
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant MF59
timeFrame: Day 50
Secondary outcomes:
measure: Treatment-emergent Serious Adverse Events (SAEs) for Participants Given Adjuvant AS03
timeFrame: Day 1 through Day 394
measure: Treatment-emergent Serious Adverse Events (SAEs) for Participants Given Adjuvant MF59
timeFrame: Day 1 through Day 394
measure: Treatment-emergent Medically Attended Adverse Events (MAAEs) for Participants Given Adjuvant AS03
timeFrame: Day 1 through Day 394
measure: Treatment-emergent Medically Attended Adverse Events (MAAEs) for Participants Given Adjuvant MF59
timeFrame: Day 1 through Day 394
measure: Treatment-emergent Potentially Immune Mediated Medical Conditions (PIMMCs) for Participants Given Adjuvant AS03
timeFrame: Day 1 through Day 394
measure: Treatment-emergent Potentially Immune Mediated Medical Conditions (PIMMCs) for Participants Given Adjuvant MF59
timeFrame: Day 1 through Day 394
measure: Treatment-emergent Unsolicited Adverse Events for Participants Given Adjuvant AS03
timeFrame: Day 1 through Day 53, which is the upper window of the Day 50 visit
measure: Treatment-emergent Unsolicited Adverse Events for Participants Given Adjuvant MF59
timeFrame: Day 1 through Day 50
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant AS03
timeFrame: Day 50
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant MF59
timeFrame: Day 50
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant AS03
timeFrame: Day 50
measure: Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Guangdong Strain for Participants Given Adjuvant AS03
timeFrame: Screening and Days 29, 50, 121 and 212
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant MF59
timeFrame: Day 50
measure: Seroconversion Based on Serum Microneutralization (MN) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant AS03
timeFrame: Days 29, 50, 121, and 212
measure: Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Guangdong Strain for Participants Given Adjuvant MF59
timeFrame: Screening and Days 29, 50, 121 and 212
measure: Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Guangdong Strain for Participants Given Adjuvant MF59
timeFrame: Day 50
measure: Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant AS03
timeFrame: Screening and Days 29, 50, 121 and 212
measure: Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant AS03
timeFrame: Day 50
measure: Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant MF59
timeFrame: Screening and Days 29, 50, 121 and 212
measure: Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant MF59
timeFrame: Day 50
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant AS03
timeFrame: Screening, Day 29, Day 121, Day 212
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant MF59
timeFrame: Screening, Day 29, Day 121, Day 212
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Hong Kong Strain for Participants Given Adjuvant AS03
timeFrame: Screening, Day 29, Day 121, Day 212
measure: Seroprotection Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Hong Kong Strain for Participants Given Adjuvant MF59
timeFrame: Screening, Day 29, Day 121, Day 212
measure: Seroconversion Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant AS03
timeFrame: Day 29, Day 50, Day 121, Day 212
measure: Seroconversion Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant MF59
timeFrame: Day 29, Day 50, Day 121, Day 212
measure: Seroconversion Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Hong Kong Strain for Participants Given Adjuvant AS03
timeFrame: Day 29, Day 50, Day 121, Day 212
measure: Seroconversion Based on Serum Hemagglutination-inhibition (HAI) Antibody Titers Against Hong Kong Strain for Participants Given Adjuvant MF59
timeFrame: Day 29, Day 50, Day 121, Day 212
measure: Seroconversion Based on Serum Microneutralization (MN) Antibody Titers Against Guangdong Strain for Participants Given Adjuvant MF59
timeFrame: Day 29, Day 50, Day 121, Day 212
measure: Seroconversion Based on Serum Microneutralization (MN) Antibody Titers Against Hong Kong Strain for Participants Given Adjuvant AS03
timeFrame: Day 29, Day 50, Day 121, Day 212
measure: Seroconversion Based on Serum Microneutralization (MN) Antibody Titers Against Hong Kong Strain for Participants Given Adjuvant MF59
timeFrame: Day 29, Day 50, Day 121, Day 212
measure: Serum Hemagglutination-inhibition (HAI) Antibody Titers Against the Guangdong Strain for Participants Given Adjuvant AS03
timeFrame: Day 50
measure: Serum Microneutralization (MN) Antibody Titers Against the Guangdong Strain for Participants Given Adjuvant AS03
timeFrame: Screening and Days 29, 50, 121 and 212
measure: Serum Microneutralization (MN) Antibody Titers Against the Guangdong Strain for Participants Given Adjuvant MF59
timeFrame: Screening and Days 29, 50, 121 and 212
measure: Serum Microneutralization (MN) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant AS03
timeFrame: Screening and Days 29, 50, 121 and 212
measure: Serum Microneutralization (MN) Antibody Titers Against the Hong Kong Strain for Participants Given Adjuvant MF59
timeFrame: Screening and Days 29, 50, 121 and 212
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Lexington
country: United States
facility: Central Kentucky Research Associates, Inc.
state: Kentucky
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc
state: New York
Study officials:
affiliation: Central Kentucky Research
name: Mark Adams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rochester Clinical Research
name: Matthew Davis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johnson County Clin-Trials
name: Carlos Fierro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heartland Research Associates
name: Terry Poling, MD
role: PRINCIPAL_INVESTIGATOR
References: