Boost-2867 COVID-19 booster given as a shot or nasal spray

A Phase 1, Open-Label, Safety and Immunogenicity Trial of Boost-2867, an IgG-Fc-RBD Fusion Protein Next Generation SARS-CoV-2 Booster Vaccine, Via Intranasal and Intramuscular Routes in Previously Vaccinated Adults

This study will test whether Boost-2867 given as a booster by injection or as a nasal spray is safe and boosts immune responses in healthy adults who were previously vaccinated for COVID-19.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years to 64 Years
• Sex: All
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Drugs / interventions: radiation
• Locations: 8 sites (San Francisco, California and 7 other locations)
• Trial ID: NCT07221162 on ClinicalTrials.gov

What this trial studies

This Phase 1, non-randomized, open-label, dose-escalation trial enrolls previously vaccinated healthy adults aged 18–64 to receive a Boost-2867 booster either intramuscularly (with or without an adjuvant) or intranasally (without adjuvant). Up to 140 participants are expected across cohorts, with each site assigned to administer only intramuscular or only intranasal dosing and cohorts enrolled sequentially. The IM arm includes one dose level without adjuvant and three dose levels with adjuvant, while the IN arm includes three dose levels without adjuvant; sentinel participants and staged dosing are used to monitor early safety. Safety, reactogenicity, and immunogenicity will be measured by clinical observation and laboratory immune assays after dosing.

Who should consider this trial

Good fit: Healthy adults aged 18–64 who were previously vaccinated against COVID-19, can comply with study visits and contraception requirements, and can attend one of the study sites are the intended participants.

Not a fit: People who are pregnant, older than 64, immunocompromised, or not previously vaccinated are excluded or less likely to receive benefit from this early-phase booster trial.

Why it matters

Potential benefit: If successful, Boost-2867 could offer a safe booster that strengthens COVID-19 immunity and, if delivered nasally, might improve mucosal protection against infection.

How similar studies have performed: Intramuscular COVID-19 booster approaches have shown effectiveness in other studies, while intranasal vaccine delivery is newer and has shown promising but limited early-stage results.

Eligibility criteria

Inclusion Criteria:

1. Provides written informed consent before initiation of any study procedures.
2. Able to understand and agree to comply with planned study procedures and be available for all study visits.
3. Non-pregnant adults, 18 through 64 years of age at the time of study product administration.
4. Participants of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception\*\*\*.

   * These criteria apply to females who are in a heterosexual relationship who are of childbearing potential. Not of childbearing potential include post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation/salpingectomy).

     * True abstinence is 100% of the time, no sexual intercourse (penis enters the vagina). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods.

       * Acceptable forms of primary contraception include a monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more before the participant's study product administration, intrauterine devices, birth control pills, and injectable/implantable/insertable/transdermal hormonal birth control products. Must have used at least one acceptable primary form of contraception for at least 30 days before study product administration and agree to continue at least one acceptable primary form of contraception through 60 days after study product administration.
5. Participants of childbearing potential must have a negative urine pregnancy test at screening and within 24 hours before study product administration.
6. In general good health\*.

   \*As determined by medical history and physical examination, including vital signs, to evaluate acute or ongoing chronic medical diagnoses/conditions that have been present for at least 90 days, which would affect the assessment of the safety of participants. Chronic medical diagnoses/ conditions should be stable for the last 30 days (i.e., no hospitalizations, ER, or urgent care for the condition). This includes no change in chronic prescription medication, dose, or frequency due to deterioration of the chronic medical diagnosis/condition 30 days before the study product administration. Any prescription change due to a change of health care provider, insurance company, etc., or done for financial reasons and in the same class of medication will not be considered a deviation of this inclusion criterion. Participants may be on chronic or as-needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity.
7. Receipt of a complete primary authorized or approved COVID-19 vaccine series and at least one booster\*.

   \* Booster may be either homologous or heterologous to the primary vaccine series. It must be an FDA-authorized/licensed vaccine, though doses may have been received during a clinical trial.
8. Clinical screening laboratory evaluations are within normal reference ranges or grade 1 with no clinical significance (NCS) per the investigator's discretion\*.

   Laboratory evaluations include White Blood Cells \[WBCs\] with differential, hemoglobin \[Hgb\], platelets \[PLTs\], Alanine Transaminase \[ALT\], Aspartate Transaminase \[AST\], Creatinine \[Cr\], Alkaline Phosphatase \[ALP\], and Total Bilirubin \[T. Bili\]). Clinical laboratory evaluations that are below the site reference range, but not graded by the toxicology table, are not exclusionary unless deemed clinically significant by an investigator.
9. Must agree to have samples stored for secondary research.

Exclusion Criteria:

1. Positive SARS-CoV-2 PCR at screening.
2. Abnormal vital signs (Grade 1 or higher):

   \*Grade 1 or higher is equivalent to: Systolic blood pressure (SBP) \>/= 141 mmHg or \</= 89 mmHg Diastolic blood pressure (DBP) \>/= 91 mmHg Heart rate (HR) is \>/= 101 beats per minute or \</= 54 beats per minute Oral temperature \>/= 38.0 degrees Celsius (100.4 degrees Fahrenheit)
3. Self-reported or medically documented SARS-CoV-2 infection (regardless of whether symptomatic or asymptomatic) within 16 weeks prior to study product administration.
4. Participant who is pregnant or breastfeeding.
5. Blood or plasma donation within 4 weeks before study product administration.
6. Receipt of antibody or blood-derived products within 90 days before study product administration.
7. Any self-reported or documented significant medical or psychiatric diseases\* or any other condition that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation.

   \*Significant medical or psychiatric conditions include but are not limited to drug or alcohol abuse within 6 months of enrollment, significant kidney disease, liver disease, ongoing malignancy, or recent diagnosis of malignancy in the last five years, excluding treated basal and squamous cell carcinoma of the skin and cervical carcinoma in situ, which are allowed.
8. Neurological conditions\*. \*Including history of Bell's palsy, history of four or more migraine headaches in the past 12 months that interfered with normal daily activity or any migraine headache in the past 5 years that required emergency or inpatient medical care, epilepsy, seizures in the last 5 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis, transverse myelitis, stroke or transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease.
9. History of significant respiratory disease currently requiring daily medications, history of asthma in the past 5 years, or any treatment of respiratory disease exacerbations in the last 5 years.
10. History of cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease), including any history of myocarditis, pericarditis, or uncontrolled cardiac arrhythmia.
11. Any autoimmune disease, including hypothyroidism, without a defined non-autoimmune cause.
12. Has an acute illness determined by the site PI or appropriate sub-investigator within 72 hours before study product administration\*.

    \*An acute illness that is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
13. Has a positive test result for hepatitis B surface antigen, hepatitis C virus RNA (by reflex testing), or human immunodeficiency virus (HIV) antigen/antibody test at screening.
14. Has any confirmed or suspected immunosuppressive or immunodeficient state such as asplenia, recurrent severe infections, and chronic\* immunosuppressant medication within the past 6 months\*\*.

    \*Chronic means more than 14 continuous days.

    \*\*Ophthalmic and topical steroids are allowed.
15. Has received any investigational study product within 60 days, or 5 half-lives, whichever is longer, before study product administration or is planning to receive one during the study.
16. Has a history of hypersensitivity or severe allergic reaction\* to any previous licensed or unlicensed study products or the candidate study product components\*\*.

    \*(e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction)

    \*\*See IB for study product formulation.
17. Received or plans to receive licensed inactivated/subunit vaccine within 14 days of study product administration or live vaccine within 28 days of study product administration.
18. Plan to receive a COVID-19 booster vaccine within the 180 days following study product administration.
19. Regular use of intranasal medications, including steroids, and sinus rinsing treatments\*.

    \*Participants must have had no intranasal medication use for 30 days before study product administration and do not plan to use intranasal medications for 30 days after study product administration for medications other than steroids and for 6 months after study product administration for intranasal steroids (including over-the-counter (OTC) fluticasone).Participants should not use nasal irrigation or sinus rinsing treatments (e.g., Neti pots or saline washes) for 28 days after the study product administration and 7 days before study visits for the duration of the trial.
20. Use of illicit intranasal drugs in the 5 years before study product administration or plans to use during the study.
21. Current smoker (including cigarettes, marijuana, and vaping) or smoking within the prior 3 months.
22. Planned international travel between product administration and Day 29 visit.
23. Any significant nasal or upper airway disease\*. \*Including, but not limited to, being prone to epistaxis, has a history of inflammatory rhinitis (including allergic rhinitis) that requires daily medications, cochlear implants, head/neck radiation history, anosmia/dysosmia, and certain ear, nose and throat (ENT) conditions, including major anatomic nasopharyngeal abnormality or sinus polyp disease due to chronic sinusitis.

Where this trial is running

San Francisco, California and 7 other locations

• University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine — San Francisco, California, United States (Recruiting)
• Center for Immunization Research, Johns Hopkins Bloomberg School Public Health — Baltimore, Maryland, United States (Recruiting)
• Saint Louis University Center for Vaccine Development — St Louis, Missouri, United States (Recruiting)
• University of Rochester Medical Center - Vaccine Research Unit — Rochester, New York, United States (Recruiting)
• Duke Vaccine and Trials Unit — Durham, North Carolina, United States (Recruiting)
• University of Pittsburgh - Medicine - Infectious Diseases — Pittsburgh, Pennsylvania, United States (Recruiting)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (Recruiting)
• Kaiser Permanente Washington Health Research Institute — Seattle, Washington, United States (Recruiting)

Conditions COVID-19; Boost-2867; coronavirus; COVID; Intramuscular; Intranasal; Next Generation Booster; Phase 1