A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine

A Phase 1, Open-Label, Safety, Reactogenicity, and Immunogenicity Trial of RVX-sCPD9, a Live-Attenuated SARS-CoV-2, as a Booster Vaccine, Via the Intranasal Route in Previously Vaccinated Adults

This phase 1 clinical trial will evaluate the safety, reactogenicity, and immunogenicity of RVX-sCPD9, given Intranasally (IN), as a booster dose to previously vaccinated healthy adults. The study is designed as a non-randomized, open-label, dose-escalation clinical trial evaluating four dose levels of RVX-sCPD9 administered IN (10^2, 10^3, 10^4, 5 x 10^4 FFU). A sample size of 80 participants (20 participants in each cohort).

The primary objective is to evaluate the safety and reactogenicity of a single IN administration of 4 ascending dosages of RVX-sCPD9 in previously vaccinated healthy adults.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID -19
• Intervention / Treatment: Biological: RVX-sCPD9

Detailed Description

This Phase 1 clinical trial will evaluate the safety, reactogenicity, and immunogenicity of RVX-sCPD9 administered as an intranasal (IN) booster in previously vaccinated healthy adults. The study is designed as a non-randomized, open-label, dose-escalation trial assessing four dose levels of RVX-sCPD9 (10^2, 10^3, 10^4, and 5 × 10^4 FFU) delivered intranasally. A total of 80 participants will be enrolled, with 20 participants in each cohort.

Eligibility will be determined at screening and confirmed again on Day 1 prior to study product administration. Participants will be healthy adults aged 18 to 64 years, regardless of prior SARS-CoV-2 infection status, who have completed a primary COVID-19 vaccination series and received at least one booster dose, with the most recent vaccination administered at least 16 weeks prior to study vaccination.

Each participant will receive a single dose of RVX-sCPD9 administered intranasally using a nasal atomization device, delivering 0.25 mL per nostril. Three sentinel participants under 50 years of age will be enrolled initially, followed by enrollment of the remaining participants.

The total study duration is approximately 1.5 years, with each participant involved for up to 7 months. The primary objective is to evaluate the safety and reactogenicity of a single intranasal administration of 4 ascending dose levels of RVX-sCPD9 in previously vaccinated healthy adults. Secondary objectives include include evaluating systemic anti-Spike humoral immune responses and evaluating nasal mucosal Immunoglobulin A (IgA) and Immunoglobulin G (IgG) responses after intranasal administration of RVX-sCPD9.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hana M El Sahly; Phone Number: 17137982058; Email: Hana.ElSahly@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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* with the last vaccination at least 16 weeks before study product administration.

   *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 (see MOP for further details).

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. See exclusion 19 for intranasal steroids.

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 vaccines 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 study 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.

24. Living with a person who has a condition that predisposes to high risk of severe COVID-19 or >/=2 conditions that predisposes to increased risk of COVID-19 per IDSA guidelines.
25. Healthcare workers with patient-facing responsibilities.
26. Resides in or works in a nursing home or other skilled nursing facility.
27. Allergy or contraindications to nirmatrelvir, ritonavir, or remdesivir.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Healthy adults will receive a single dose of 1x10^2 FFU RVX-sCPD9 vaccine. It will be administered intranasally through a nasal atomization device with a spray divider to provide 0.25mL in each nostril. 3 sentinel participants, under 50 years of age, will be enrolled first and then the reminder. N= 20	Biological: RVX-sCPD9; RVX-sCPD9 is a live-attenuated SARS-CoV-2 vaccine candidate engineered from the ancestral B.1 strain for intranasal administration to prevent coronavirus disease 2019 (COVID-19) and reduce viral transmission. The vaccine was generated through two complementary attenuation strategies: a codon-pair-deoptimization of the viral genome that reduced viral fitness while preserving protein amino acid sequence, and a deletion of the spike furin cleavage site (FCS), a modification known to prevent horizontal transmission and further attenuate pathogenicity.
Experimental: Arm 2; Healthy adults will receive a single dose of 1x10^3 FFU RVX-sCPD9 vaccine. It will be administered intranasally through a nasal atomization device with a spray divider to provide 0.25mL in each nostril. 3 sentinel participants, under 50 years of age, will be enrolled first and then the reminder. N= 20	Biological: RVX-sCPD9; RVX-sCPD9 is a live-attenuated SARS-CoV-2 vaccine candidate engineered from the ancestral B.1 strain for intranasal administration to prevent coronavirus disease 2019 (COVID-19) and reduce viral transmission. The vaccine was generated through two complementary attenuation strategies: a codon-pair-deoptimization of the viral genome that reduced viral fitness while preserving protein amino acid sequence, and a deletion of the spike furin cleavage site (FCS), a modification known to prevent horizontal transmission and further attenuate pathogenicity.
Experimental: Arm 3; Healthy adults will receive a single dose of 1x10^4 FFU RVX-sCPD9 vaccine. It will be administered intranasally through a nasal atomization device with a spray divider to provide 0.25mL in each nostril. 3 sentinel participants, under 50 years of age, will be enrolled first and then the reminder. N= 20	Biological: RVX-sCPD9; RVX-sCPD9 is a live-attenuated SARS-CoV-2 vaccine candidate engineered from the ancestral B.1 strain for intranasal administration to prevent coronavirus disease 2019 (COVID-19) and reduce viral transmission. The vaccine was generated through two complementary attenuation strategies: a codon-pair-deoptimization of the viral genome that reduced viral fitness while preserving protein amino acid sequence, and a deletion of the spike furin cleavage site (FCS), a modification known to prevent horizontal transmission and further attenuate pathogenicity.
Experimental: Arm 4; Healthy adults will receive a single dose of 5x10^4 FFU RVX-sCPD9 vaccine. It will be administered intranasally through a nasal atomization device with a spray divider to provide 0.25mL in each nostril. 3 sentinel participants, under 50 years of age, will be enrolled first and then the reminder. N= 20	Biological: RVX-sCPD9; RVX-sCPD9 is a live-attenuated SARS-CoV-2 vaccine candidate engineered from the ancestral B.1 strain for intranasal administration to prevent coronavirus disease 2019 (COVID-19) and reduce viral transmission. The vaccine was generated through two complementary attenuation strategies: a codon-pair-deoptimization of the viral genome that reduced viral fitness while preserving protein amino acid sequence, and a deletion of the spike furin cleavage site (FCS), a modification known to prevent horizontal transmission and further attenuate pathogenicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of abnormal clinical safety laboratory adverse events (AEs)	Through Day 15
Occurrence of Adverse Events of Special Interest (AESIs)	Through Day 181
Occurrence of Medically-Attended Adverse Events (MAAEs)	Through Day 181
Occurrence of solicited local adverse events (AEs)	Through Day 15
Occurrence of solicited systemic adverse events (AEs)	Through Day 15
Occurrence of unsolicited adverse events (AEs)	Through Day 29
Occurrence of New-Onset Chronic Medical Conditions (NOCMCs)	Through Day 181
Occurrence of Serious Adverse Events (SAEs)	Through Day 181

Secondary Outcome Measures

Outcome Measure	Time Frame
Nasal mucosal Immunoglobulin A (IgA) anti-S binding antibodies	Through Day 181
Nasal mucosal Immunoglobulin G (IgG) anti-S binding antibodies	Through Day 181
Serum anti-S binding Immunoglobulin A (IgA) antibodies	Through Day 181
Serum anti-S binding Immunoglobulin G (IgG) antibodies	Through Day 181
Serum anti-S neutralizing antibodies	Through Day 181

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): November 15, 2027
• Study Completion (Estimated): November 15, 2027

Study Registration Dates

• First Submitted: July 9, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 9, 2026

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Vaccine; Coronavirus; Phase 1; COVID; Intranasal; Boost; Next Generation; Boster; RVX-sCPD9
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coronavirus Infections
• Other Study ID Numbers: 25-1107

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No