BPL-1357 influenza vaccine by nasal spray or injection for H1N1 exposure

Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study of the Safety and Efficacy of BPL-1357 Against H1N1 Influenza Virus Challenge

Test whether two doses of the BPL-1357 flu vaccine, given by nasal spray or by injection, protect healthy adults 18–55 from H1N1 after controlled exposure.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 129 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 2 sites (Bethesda, Maryland and 1 other locations)
• Trial ID: NCT07215858 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled phase 2 trial testing a beta-propiolactone (BPL)-inactivated quadruple influenza vaccine given intramuscularly or intranasally in two doses 28 days apart. Participants are randomized to receive IM vaccine with IN placebo, IN vaccine with IM placebo, or double placebo during the vaccination phase, then undergo a controlled H1N1 influenza challenge as inpatients in the challenge phase. Primary outcomes include safety and prevention of mild-to-moderate influenza disease after challenge, with secondary endpoints such as symptom scores and viral shedding by qRT-PCR. The overall study duration for participants is about 5 to 8 months and is conducted at multiple U.S. clinical sites.

Who should consider this trial

Good fit: Healthy, non-smoking adults aged 18–55 who have not had recent influenza vaccination and who are willing to comply with inpatient challenge procedures are ideal candidates.

Not a fit: People over 55, those with significant chronic illnesses, immunocompromised individuals, pregnant people, current smokers, or those recently vaccinated for influenza would likely not benefit or be ineligible.

Why it matters

Potential benefit: If successful, the vaccine could reduce symptomatic H1N1 illness and help guide broader pandemic influenza vaccine strategies.

How similar studies have performed: Human influenza challenge trials have previously shown that some candidate vaccines can reduce symptoms and viral shedding, but using a BPL-inactivated quadruple cocktail in this exact format is relatively novel.

Eligibility criteria

* INCLUSION CRITERIA:

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

1. Adults \>=18 and \<= 55 years of age at the time of consent.
2. Able to provide written informed consent.
3. Non-smoker (i.e., tobacco and cannabis) and does not use vape or e-cigarette products currently. Also, must not have used any of these products extensively in the past (regular use more than 5 times per week, more than 6 months lifetime total).
4. Has not received influenza vaccination of any type within 6 months prior to enrollment and consents to not receive influenza vaccination of any type until after the end of study participation (PBD63).
5. Has not received any other vaccination of any type within 4 weeks prior to enrollment and consents to not receive any unlicensed vaccine until after the end of the study (PBD63).
6. Has not received any broadly protective influenza vaccine in the past.
7. Participants of childbearing potential must meet one of the following criteria through the end of study participation (PBD63):

   1. Is infertile, including postmenopausal status (as defined by age .45 years plus no menses for \>= 1 year without an alternative medical cause) or history of hysterectomy or bilateral oophorectomy.
   2. Agrees that, when engaging in intercourse that can result in pregnancy, they will use an acceptable or highly effective form of contraception, and their male partner will use a condom with spermicide. Acceptable methods of female contraception include

   the following:
   * Bilateral tubal ligation
   * Implant of levonorgestrel
   * Injectable progestogen
   * Oral contraceptive pills
   * Diaphragm with spermicide
   * Intrauterine device (IUD)
   * Sexual abstinence
   * Vasectomized partner
8. Able to speak and understand English (NIH).
9. Able to speak and understand English and/or Spanish (UTMB).
10. A negative HIV test within 6 months before enrollment.
11. Has not used IN medications (including but not limited to nasal sprays, sinus rinses), and has not routinely used 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 (about 2 weeks) prior to study enrollment and agrees not to use these medications until after the end of study participation (PBD63), unless approved by the investigator.
12. Agrees not to donate blood or blood products from enrollment through the final study visit (PBD63).
13. Not planning on cohabitating with any high-risk individuals (e.g., infants, elderly, those with high-risk conditions (e.g., pregnancy, medical conditions such as those outlined in exclusion criterion 1) for at least 2 weeks after discharge from the inpatient portion of this study.
14. Participant is willing and able to comply with all trial procedures.

EXCLUSION CRITERIA

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

1. Current medical conditions (self-reported or medically documented) including but not limited to:

   1. Chronic pulmonary disease (e.g., asthma, emphysema).
   2. Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
   3. Chronic medical conditions requiring close medical follow-up or hospitalization (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
   4. Immunosuppression, immune deficiency, or ongoing malignancy.
   5. Neurological and neurodevelopmental condition (e.g., Bell s palsy, cerebral palsy, epilepsy, seizures).
2. Body mass index (BMI) \<18 and \>35.
3. Pregnant or breastfeeding.
4. History of postinfectious or postvaccine neurological sequelae including GBS.
5. History of stroke within the past 5 years.
6. Acute illness within 7 days prior to enrollment (PAD0).
7. Known allergy to influenza vaccination or components contained in the influenza vaccine being used.
8. Known allergy to influenza treatments (including oseltamivir or nonsteroidal anti-inflammatory medications).
9. Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins, fluoroquinolones, or glycopeptides).
10. Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
11. Receipt of any unlicensed drug or investigational agent within 3 months or 5.5 half-life (whichever is greater) prior to enrollment.
12. Receipt of any unlicensed vaccine within 6 months prior to enrollment.
13. Self-reported or known history of alcoholism or drug abuse or use within 6 months prior to enrollment, or positive urine test for illicit drugs (i.e., amphetamines, cocaine metabolites, benzodiazepines, opiates, but not tetrahydrocannabinol) prior to vaccination on PAD0.
14. Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the PI to be a contraindication to protocol participation.
15. History of angioedema or anaphylaxis.
16. Study site staff who directly report to the study or site PI are excluded from participation.
17. Any condition, event or lab value that, in the judgment of the investigator, is a contraindication to protocol participation or would place the participant at increased risk for participation.
18. Any condition or event that, in the judgment of the investigator, impairs the participant's ability to give informed consent.

Individuals meeting any of the following criteria will be excluded from participation in Phase B:

1. Positive urine test for illicit drugs (i.e., amphetamines, cocaine metabolites, benzodiazepines, opiates, but not tetrahydrocannabinol) prior to inoculation (PBD0).
2. Acute illness within 7 days prior to inoculation with the human challenge virus (PBD0).
3. Grade 3 or greater sign, symptom, or lab abnormality that is clinically significant and (in the opinion of the site PI) puts the participant at higher risk of adverse effects with influenza challenge.
4. Pregnant or breastfeeding.
5. Positive test for influenza within 8 weeks prior to challenge.

Where this trial is running

Bethesda, Maryland and 1 other locations

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
• University of Texas Medical Branch, Galveston — Galveston, Texas, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: Luca T Giurgea, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Luca T Giurgea, M.D.

Conditions Influenza; Human; Vaccine; Human Challenge