Safety and Immunogenicity of BPL-1357, A BPL-Inactivated, Whole-Virus, Universal Influenza Vaccine

• ClinicalTrials.gov Identifier: NCT05027932
• Recruitment Status: Active, not recruiting
• First Posted: August 31, 2021
• Last Update Posted: June 1, 2023
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Description

Brief Summary:

Background:

Influenza (flu) is a virus that infects people of all ages. Some people may have mild flu symptoms. Others may get very sick and even die from the flu. Flu vaccines help protect people against the flu, but if the flu strains in the vaccine are not a good match with the strains circulating in the community, the vaccine is not as effective. Researchers want to make flu vaccines that protect against changing flu strains.

Objective:

To test if a new flu vaccine is safe and if it creates an immune response.

Eligibility:

Healthy adults ages 18-55 who do not smoke and have not received a flu vaccine in the 8 weeks prior or a COVID-19 vaccine in the 4 weeks prior to enrollment.

Design:

Participants will be screened on a separate protocol.

Participants will have 9 visits over 7 months. They will get a combination of study vaccine and/or placebo, both as a shot in the arm and as a spray into the nose, at 2 visits. For 7 days after getting the vaccines, they will take their temperature and complete online surveys at home to record any symptoms.

At each visit, participants will have a physical exam and medical history. They will give blood and urine samples. They will have nasal testing. For this, a thin absorptive strip will be inserted into their nostril for 1 minute to collect mucus. At some visits, the inside of their nose will be wiped with a small brush to collect cells. For this, their nostril will be numbed to make it more comfortable. Some blood and nasal samples will be used for genetic testing. Participants who get flu-like symptoms during the study will be asked to collect nasal samples at home and send these samples back to NIH to test if they actually have the flu.

Condition or disease	Intervention/treatment	Phase
Influenza	Other: IN Placebo; Other: IM Placebo; Drug: BPL-1357	Phase 1

Detailed Description:

Study Description: This is a randomized, double-blinded, placebo-controlled, single-center, phase 1 clinical trial of beta-propiolactone (BPL)- inactivated quadruple influenza virus cocktail vaccine (BPL-1357) administered intramuscularly (IM) or intranasally (IN) in 2 doses 28 days apart. Participants will be randomized to one of three groups for treatment assignment. The primary hypothesis is that IN and IM BPL-1357 will be well tolerated.

Objectives:

Primary Objective:

1. To assess the safety of BPL-1357 given IM or IN, compared to placebo.

Secondary Objective:

1. To further assess the safety of BPL-1357 given IM or IN, compared to placebo.
2. To assess the immunogenicity of BPL-1357 given IM or IN, compared to placebo.

Tertiary Objective:

1. To characterize the systemic and mucosal humoral immune responses induced by BPL-1357 given IM or IN, compared to placebo.
2. To further characterize the immune response induced by BPL-1357 given IM or IN through variable, diversity, and joining (VDJ) gene repertoire analysis, cytokine analysis, cytometry, transcriptomics, and assessment of T-cell responses.
3. To assess the rates of influenza disease among groups given IM or IN BPL-1357 compared to placebo.

Endpoints:

Primary Endpoints:

1. Type and severity (by grading) of adverse events (AEs) through V2D28 [28 days after vaccine dose 2].
2. Type of serious adverse events (SAEs) through V2D28 [28 days after vaccine dose 2].

Secondary Endpoints:

1. Safety

   1. Type and severity (by grading) of AEs through V2D182 [182 days after vaccine dose 2].
   2. Type of SAEs through V2D182 [182 days after vaccine dose 2].

2. Immunogenicity

   1. Antibodies against H1, H3, H5, and H7 head and stalk as measured by hemagglutination inhibition (HAI) or enzyme-linked immunosorbent assay (ELISA) from blood and mucosal samples at V2D28.
   2. Antibodies against N1, N3, N8, and N9 as measured by neuraminidase inhibition (NAI) or ELISA from blood and mucosal samples at V2D28.

Tertiary Endpoints:

1. Additional antibody titer characterization via:

   1. Antibodies against H1, H3, H5, and H7 head and stalk as measured by HAI or ELISA from blood and mucosal samples at V1D7, V1D14, V1D28, V2D7, V2D14, V2D56, and V2D182.
   2. Antibodies against N1, N3, N8, and N9 as measured by NAI or ELISA from blood and mucosal samples at V1D7, V1D14, V1D28, V2D7, V2D14, V2D56, and V2D182.

2. Additional immune response characterization via:

   1. VDJ gene repertoire analysis.
   2. Cytokine analysis.
   3. Flow cytometric phenotyping of lymphocytes.
   4. Transcriptomic gene expression.
   5. T-cell responses.
3. Influenza disease

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of the Safety and Immunogenicity of BPL-1357, A BPL-Inactivated, Whole-Virus, Universal Influenza Vaccine
• Actual Study Start Date: June 27, 2022
• Estimated Primary Completion Date: March 1, 2024
• Estimated Study Completion Date: March 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A; 15 participants receiving IM BPL1357 & IN Placebo	Other: IN Placebo; The placebo will be normal saline in two syringes administered IN.; Drug: BPL-1357; BPL-1357 contains 4 whole inactivated avian influenza viruses: A /Environment /Maryland/261/2006 H7N3, A/Mallard /Maryland/802/2007 H5N1, A/Pintail/Ohio /339/1987 H3N8, and A/Mallard/Ohio /265/1987 H1N9. It will be administered either IM or IN depending on the assigned treatment group.
Experimental: Group B; 15 participants receiving IN BPL1357 & IM Placebo	Other: IM Placebo; The placebo will be normal saline in a syringe administered IM.; Drug: BPL-1357; BPL-1357 contains 4 whole inactivated avian influenza viruses: A /Environment /Maryland/261/2006 H7N3, A/Mallard /Maryland/802/2007 H5N1, A/Pintail/Ohio /339/1987 H3N8, and A/Mallard/Ohio /265/1987 H1N9. It will be administered either IM or IN depending on the assigned treatment group.
Sham Comparator: Group C; 15 participants receiving IM and IN placebo	Other: IN Placebo; The placebo will be normal saline in two syringes administered IN.; Other: IM Placebo; The placebo will be normal saline in a syringe administered IM.

Outcome Measures

Primary Outcome Measures :

1. Safety - Serious Adverse Event [ Time Frame: V2D28 (Day 56) ]
   Type of SAEs through day V2D28.
2. Safety - Adverse Events [ Time Frame: V2D28 (Day 56) ]
   Type and severity (by grading) of AEs through day V2D28.

Secondary Outcome Measures :

1. Safety - Serious Adverse Event [ Time Frame: V2D182 (Day 210) ]
   Type of SAEs through day V2D182
2. Safety - Adverse Events [ Time Frame: V2D182 (Day 210) ]
   Type and severity (by grading) of AEs through day V2D182
3. Immunogenicity - Systemic and Mucosal Immune Responses against Neuraminidase [ Time Frame: V2D28 (Day 56) ]
   Antibodies against N1, N3, N8, and N9 as measured by NAI or ELISA from blood and mucosal samples at V2D28
4. Immunogenicity - Systemic and Mucosal Immune Responses against Hemagglutinin [ Time Frame: V2D28 (Day 56) ]
   Antibodies against H1, H3, H5, and H7 head and stalk as measured by HAI or ELISA from blood and mucosal samples at V2D28

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:

Individuals must meet all of the following criteria to be eligible for study participation:

• 18 and <= 55 years of age.

  • Non-smoker (tobacco and cannabis) and does not use vape or e-cigarette products.
  • Has not received influenza vaccination of any type in the 8 weeks prior to enrollment and willing to not receive influenza vaccination of any type until after the V2D56 visit. Participants who enroll in our study will be informed of the Centers for Disease Control and Prevention (CDC) recommendation to receive seasonal influenza vaccination annually.
  • Has not received Coronavirus Disease 19 (COVID-19) vaccination of any type in the 4 weeks prior to enrollment and willing to not receive COVID-19 vaccination of any type after the V2D28 visit. Participants who enroll in our study who are interested in getting a COVID-19 vaccination will be counselled to receive it prior to enrolling into our study.

  • A female participant is eligible for this study if she is not pregnant or breastfeeding and meets one of the following criteria, beginning at least 4 weeks prior to enrollment through the end of the study period (V2D182):

    • Is infertile, including postmenopausal status (as defined by no menses for >= 1 year) or history of hysterectomy or bilateral oophorectomy.
    • Agrees to practice abstinence.
    • Agrees that, with heterosexual intercourse with a fertile male partner, she will use an acceptable form of contraception and her male partner will use a condom with spermicide. Acceptable effective methods of female contraception include the following: bilateral tubal ligation, implant of levonorgestrel, injectable progestogen, intrauterine device, oral contraceptive pills, and diaphragm with spermicide.
  • Able to provide informed consent.
  • Able to speak English.
  • Human immunodeficiency virus (HIV) uninfected with a negative test within 60 days of enrollment.
  • Does not use IN medications (including but not limited to nasal sprays, sinus rinses), over-the-counter medications (including but not limited to aspirin, decongestants, antihistamines, and other nonsteroidal anti-inflammatory drugs), and herbal medications (including but not limited to herbal tea or St. John s Wort) within 14 days prior to study enrollment, and agrees not to use these mediations through the final study visit, unless approved by the investigator.
  • Agrees not to donate blood or blood products from 3 months prior to enrollment through the final study visit.

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

• Presence of self-reported or medically documented significant medical condition including but not limited to:

  • Chronic pulmonary disease (e.g., asthma, emphysema).
  • Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
  • Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
  • Immunosuppression, immune deficiency, or ongoing malignancy.
  • Neurological and neurodevelopmental conditions (e.g., Bell s palsy, cerebral palsy, epilepsy, stroke, seizures).
  • Postinfectious or postvaccine neurological sequelae including GBS.
  • Body mass index (BMI) <= 18 and >= 35.
• Acute illness within 7 days prior to enrollment.
• Individuals who have grade 2 or above clinically significant laboratory values outside the limits thus specified by normal laboratory parameters.
• Known allergy to influenza vaccination or excipients contained in the influenza vaccine used.
• Known allergy to lidocaine or phenylephrine.
• Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
• Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) prior to enrollment.
• Receipt of any unlicensed vaccine within 6 months prior to enrollment, not including COVID-19 vaccines under Emergency Use Authorization.
• Self-reported or known history of alcoholism or drug abuse within 6 months prior to enrollment, or positive urine test for drugs of abuse (i.e., amphetamines, cocaine metabolites, benzodiazepines, opiates, or tetrahydrocannabinol) prior to vaccination on V1D0.
• Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the principal investigator (PI) to be a contraindication to protocol participation.
• History of angioedema or anaphylaxis.
• History of SARS-COV-2 infection with residual or ongoing symptoms.
• Any condition or event that, in the judgment of the PI, is a contraindication to protocol participation or impairs the participant s ability to give informed consent.

Contacts and Locations

Locations

United States, Maryland

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Matthew J Memoli, M.D.; National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT05027932
• Other Study ID Numbers: 10000320; 000320-I
• First Posted: August 31, 2021
• Last Update Posted: June 1, 2023
• Last Verified: May 30, 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: .We are not working with any outside collaborators that require this information.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

Flu; Immunity; Virology; Investigational; Healthy Volunteer

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases