NDV-HXP-S Vaccine for COVID-19

Overseen By Geneva Ortiz

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Sean Liu

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: COVID-19, Immunocompromised, Pregnancy, others

Compensation: Varies

Number of Visits: 1

Duration: 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new COVID-19 vaccine, NDV-HXP-S, to assess its safety and the body's response. Researchers administer the vaccine using different methods: a nasal spray (IN), a shot in the arm (IM), or both, to healthy adults already vaccinated against COVID-19. The trial seeks participants who have been COVID-free, received their last COVID-19 shot over six months ago, and have no history of severe allergies or immune issues. Participants will be closely monitored after receiving the vaccine and must follow specific guidelines, such as home isolation, during the study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the unique opportunity to be among the first to receive this new vaccine.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it excludes those using immunosuppressive medications. It's best to discuss your specific medications with the trial investigator.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the NDV-HXP-S vaccine, designed to protect against COVID-19, is generally safe. Early safety results indicate that the vaccine is well-tolerated when administered intranasally or intramuscularly. Studies found no serious side effects from higher doses.

For those considering the high dose given both intranasally and intramuscularly (IN+IM), earlier studies found it safe and capable of triggering a strong immune response. The high dose given only intranasally (IN) was also safe and effective in protecting animals against various COVID-19 variants. As for the high dose given only intramuscularly (IM), studies reported it to be safe with strong immune responses.

Similarly, low doses, whether given intranasally, intramuscularly, or both, have been found to be safe. They showed no serious side effects and effectively boosted the body's defenses.

These findings suggest that the NDV-HXP-S vaccine, in its various forms, is safe and generally well-tolerated, offering reassurance to those considering joining a trial for this vaccine. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the NDV-HXP-S vaccine for COVID-19 because it uses a new method of delivery and a novel vaccine platform. This vaccine is derived from a Newcastle disease virus, which is engineered to produce the spike protein of the coronavirus, potentially triggering a strong immune response. Unlike current vaccines that are primarily injected, NDV-HXP-S can be administered both intranasally (IN) and intramuscularly (IM), which might enhance its effectiveness by mimicking natural infection routes and providing broader protection. Additionally, its unique approach could lead to easier manufacturing and distribution, potentially making it more accessible globally.

What evidence suggests that this trial's treatments could be effective for COVID-19?

Research has shown that the NDV-HXP-S vaccine could effectively protect against COVID-19. Animal studies with hamsters and mice demonstrated that the vaccine, particularly when administered nasally, can protect against various virus variants, such as Delta and Omicron. This method also appears to reduce the virus's spread from the upper airways. Early human trials indicated that the vaccine is safe and generally well-tolerated. In this trial, participants will receive the NDV-HXP-S vaccine in different cohorts: some nasally (IN), others by intramuscular injection (IM), and some with a combination of both methods. Higher doses have triggered immune responses, supporting the vaccine's potential to prevent COVID-19. ^{1 3 4 6 7}

Who Is on the Research Team?

Sean Liu, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults aged 18-59 who've completed an FDA-approved COVID-19 vaccine series at least 6 months ago, not pregnant/breastfeeding, agree to contraception and no other clinical trials for a year. Excludes those with certain diseases (HIV, hepatitis), severe vaccine reactions, or immunocompromising conditions.

Inclusion Criteria

I am not pregnant or breastfeeding and follow the required contraceptive guidelines.

Willing and able to provide written informed consent prior to performing study procedures

I have not had COVID-19, tested negative, and have no symptoms.

Exclusion Criteria

You have a high level of COVID-19 antibodies or tested negative for COVID-19 antibodies.

I am currently taking or have recently taken drugs that weaken my immune system.

You have been exposed to Newcastle Disease Virus (NDV) through handling birds, working on a poultry farm, or doing research with the virus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NDV-HXP-S vaccine or placebo in an ambulatory setting, followed by home isolation with daily at-home sample collection and online symptom reporting

14 days

1 visit (in-person), daily monitoring (remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of adverse events

365 days

What Are the Treatments Tested in This Trial?

Interventions

• NDV-HXP-S

Trial Overview The trial is testing two dosages of NDV-HXP-S, a live recombinant Newcastle disease virus-based COVID-19 vaccine given by intramuscular (IM) injection or nasal spray (IN). Participants will be compared to those receiving saline placebo.

How Is the Trial Designed?

Group I: Cohort 7: NDV-HXP-S high dose IN+IM in combination Active Control 2 Interventions

Participants in Cohort 7 (high, IN+IM) will receive high doses of NDV-HXP-S at 1x109 EID50. Participants will only enroll into Cohort 7 if Cohort 4 did not have an SAE that required additional participants. Participants will be given NDV-HXP-S in an ambulatory setting and be monitored by the research staff for 4 hours post-administration. Participants will then return home under home isolation. Home isolation will require daily at-home sample collection and online symptom reporting. Discontinuation of home isolation will require laboratory confirmation of negative NDV-HXP-S virus detection.

Group II: Cohort 5: NDV-HXP-S high dose IN Active Control 1 Intervention

Participants in Cohort 5 (high, IN) will receive high doses of NDV-HXP-S at 1x109 EID50. Participants will ONLY enroll into Cohort 5 if Cohort 2 (low dose IN) did not have any SAEs that required additional participants. Participants will be given NDV-HXP-S in an ambulatory setting and be monitored by the research staff for 4 hours post-administration. Participants will then return home under home isolation. Home isolation will require daily at-home sample collections and online symptom reporting. Discontinuation of home isolation will require laboratory confirmation of negative NDV-HXP-S virus detection.

Group III: Cohort 6: NDV-HXP-S high dose IM Active Control 1 Intervention

Participants in Cohort 6 (high, IM) will receive high doses of NDV-HXP-S at 1x109 EID50. Participants will ONLY enroll into Cohort 6 if Cohort 3 (low dose IM) did not have any SAEs that required additional participants. Participants will be given NDV-HXP-S in an ambulatory setting and be monitored by the research staff for 4 hours post-administration. Participants will then return home under home isolation. Home isolation will require daily at-home sample collections and online symptom reporting. Discontinuation of home isolation will require laboratory confirmation of negative NDV-HXP-S virus detection.

Group IV: Cohort 4: NDV-HXP-S low dose IN+IM in combination Active Control 2 Interventions

Participants in Cohort 4 (low, IN+IM) will receive low doses of NDV-HXP-S at 3.3x108 EID50. Participants will be given NDV-HXP-S in an ambulatory setting where IN and IM doses will be given in succession. Participants will be monitored by the research staff for 4 hours post-administration. Participants will then return home under home isolation. Home isolation will require daily at-home sample collections and online symptom reporting. Discontinuation of home isolation will require laboratory confirmation of negative NDV-HXP-S virus detection.

Group V: Cohort 2: NDV-HXP-S low dose IN Active Control 1 Intervention

Participants in Cohort 2 (low, IN) will receive a single administration of a low dose of NDV-HXP-S at 3.3x108 Egg-Infectious Dose50 (EID50). Participants will be given NDV-HXP-S in an ambulatory setting and be monitored by the research staff for 4 hours post-administration. Participants will then return home under home isolation. Home isolation will require daily at-home sample collections and online symptom reporting. Discontinuation of home isolation will require laboratory confirmation of negative NDV-HXP-S virus detection.

Group VI: Cohort 3: NDV-HXP-S low dose IM Active Control 1 Intervention

Participants in Cohort 3 (low, IM) will receive a single administration of a low dose of NDV-HXP-S at 3.3x108 Egg-Infectious Dose50 (EID50). Participants will be given NDV-HXP-S in an ambulatory setting and be monitored by the research staff for 4 hours post-administration. Participants will then return home under home isolation. Home isolation will require daily at-home sample collections and online symptom reporting. Discontinuation of home isolation will require laboratory confirmation of negative NDV-HXP-S virus detection.

Group VII: Cohort 1: Placebo / Sodium Chloride Placebo Group 1 Intervention

Participants in Cohort 1 will receive placebo given IN+IM in combination. Placebo administration will be given in an ambulatory setting. IN administration will be immediately followed by IM administration. Participants will be monitored by the research staff for 1-hour after administration. Participants will be permitted to receive any additional federally authorized or approved vaccines 56 days after receiving placebo.

Who Is Running the Clinical Trial?

Sean Liu

Lead Sponsor

Trials

1

Recruited

40+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05181709

A Live Recombinant Newcastle Disease Virus-vectored ... Primary Study Objective: To evaluate the safety and tolerability profile of two dose levels of the NDV-HXP-S vaccine as an IN, IM, or a combined administration ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9241906/

Trivalent NDV-HXP-S Vaccine Protects against ... Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05940194

NDV-HXP-S Vaccine Clinical Trial (COVIVAC) In Part 2 of this combined Phase 1/2 study, 374 adults aged 18-75 years will be randomized (1:1:1) to placebo, or COVIVAC 3 µg being evaluated in Phase 1 or the ...

4. nature.com nature.com/articles/s41541-024-00870-8

Intranasal vaccination with an NDV-vectored SARS-CoV-2 ... Overall, our data indicate that one or two intranasal doses of NDV-PFS can provide robust protection against disease and viral replication ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11955676/

Mucosal multivalent NDV-based vaccine provides cross- ... Overall, a mucosal multivalent live NDV-HXP-S vaccine shows great promise as a safe, next-generation vaccine conferring broad mucosal and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10170424/

Interim safety and immunogenicity results from an NDV- ... Here, we tested a live version of the vaccine, AVX/COVID-12-HEXAPRO (Patria, also known as NDV-HXP-S), in an open-label, non-randomized non- ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2589537022000530

Safety and immunogenicity of an inactivated recombinant ... NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 μg and 3 μg+CpG1018 formulations advanced to phase 2.