RSV Vaccination + Immunization for Respiratory Syncytial Virus

Recruiting at 7 trial locations

Overseen By Christina Rostad

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

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

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Psychiatric disease, Immune impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 12 months

400 Participants Needed

Trial Summary

What is the purpose of this trial?

Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) in infants and young children. It is also a leading cause of mortality in children \<5 years of age worldwide. Until recently, no Food and Drug Administration (FDA)-approved vaccines were available to prevent RSV infection. The only prophylactic product for RSV prevention recommended for infants was the monoclonal antibody palivizumab, but administration was limited to those with extreme prematurity, chronic lung disease, or hemodynamically significant congenital heart disease. However, in 2023, the FDA approved two products designed to prevent RSV lower respiratory tract disease (LRTD) in all infants: an active RSV vaccine based on the prefusion F protein (RSVpreF, ABRYSVO, Pfizer) administered during pregnancy, and a passive, long-acting monoclonal antibody (nirsevimab-alip \[henceforth referred to as nirsevimab\], BEYFORTUS, AstraZeneca) administered to infants at birth or at the start of their first RSV season. Both products were evaluated in Phase 3 pivotal clinical trials and have high efficacy in preventing LRTD caused by RSV in infants. Although there is no established correlate of protection against RSV, antibodies have been associated with protection across multiple studies. The clinical development plan for the products did not include comprehensive evaluations of the magnitude and durability of the immune response, nor were the two products tested in a single trial. This study is a prospective, randomized, open-label Phase 4 study with the primary objective of evaluating the magnitude and durability of RSV-specific neutralizing antibodies in infants through 12 months of life following either maternal RSV vaccination, infant nirsevimab administration, or both products combined.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have taken immunosuppressive drugs or certain biologic agents within 30 days before enrolling. Inhaled, topical, or certain other forms of steroids are allowed.

What data supports the effectiveness of the drug Nirsevimab for preventing respiratory syncytial virus (RSV) infection?

Nirsevimab has been shown to be effective in preventing RSV infection in newborns and infants during their first RSV season, as demonstrated by positive results in Phase 2b and 3 clinical trials. It is a long-acting antibody that targets a specific part of the RSV virus, allowing for a single dose to provide protection throughout the RSV season. ^{1 2 3 4 5}

Is the RSV treatment Nirsevimab safe for humans?

Nirsevimab has been approved for preventing RSV infection in newborns and infants based on positive results from clinical trials, indicating it is generally safe for this use. ^{1 4 6 7 8}

How is the drug Abrysvo, Beyfortus different from other RSV treatments?

Abrysvo and Beyfortus are unique because they offer a long-acting protection against RSV with a single dose, unlike the existing option palivizumab, which requires monthly injections. Beyfortus (Nirsevimab) specifically targets a stable part of the RSV virus, providing effective prevention for infants during their first RSV season. ^{1 3 4 5 9}

Eligibility Criteria

This trial is for healthy infants at risk of Respiratory Syncytial Virus (RSV) infection. It includes those whose mothers are vaccinated during pregnancy with ABRYSVO and infants receiving BEYFORTUS at birth or the start of RSV season. Specific eligibility criteria were not provided.

Inclusion Criteria

I am between 18-45 years old, pregnant with one baby, and not at high risk for pregnancy complications.

Understands and agrees to comply with all study procedures

I plan to give birth in a hospital or facility that can perform study procedures.

Exclusion Criteria

Maternal conditions known to impair transplacental transfer of maternal antibodies (e.g., placental pathology, hypergammaglobulinemia, HIV)

Maternal history of preterm birth (<34 weeks GA)

I have a condition that makes bleeding more likely or can't have shots in my muscles.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Mothers receive RSVpreF vaccine during pregnancy and infants receive nirsevimab at birth or at 3 months

12 months

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at Day 1, 43, 91, 181, and 366

Treatment Details

Interventions

• Abrysvo
• Beyfortus

Trial Overview The study tests the immune response in infants to either maternal vaccination with ABRYSVO, infant immunization with BEYFORTUS, or both. It's a Phase 4 trial aiming to understand how well these interventions protect against RSV over the first year of life.

Participant Groups

Group I: Group 2 Experimental Treatment 1 Intervention

Mother does NOT receive maternal RSVpreF and infant receives one dose of nirsevimab (BEYFORTUS) 50mg/0.5mL if body weight \<5kg or 100mg/mL if body weight is \>= 5kg at birth . N= 50.

Group II: Group 1C Experimental Treatment 2 Interventions

Mother receives 120 mcg/0.5ml of maternal RSVpreF (ABRYSVO) administered intramuscularly once during 32 0/7 to 36 6/7 weeks GA and infant receives one dose of nirsevimab (BEYFORTUS) 50mg/0.5mL if body weight \<5kg or 100mg/mL if body weight is \>= 5kg at 3-month . N= 50.

Group III: Group 1B Experimental Treatment 2 Interventions

Mother receives 120 mcg/0.5ml of maternal RSVpreF (ABRYSVO) administered intramuscularly once during 32 0/7 to 36 6/7 weeks GA and infant receives one dose of nirsevimab (BEYFORTUS) 50mg/0.5mL if body weight \<5kg or 100mg/mL if body weight is \>= 5kg at birth. N= 50.

Group IV: Group 1A Experimental Treatment 1 Intervention

Mother receives 120 mcg/0.5ml of maternal RSVpreF (ABRYSVO) administered intramuscularly once during 32 0/7 to 36 6/7 weeks GA and infant does NOT receive nirsevimab. N= 50.

Abrysvo is already approved in United States for the following indications:

Approved in United States as ABRYSVO for:

• Prevention of RSV lower respiratory tract disease in infants

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

Nirsevimab is a newly approved long-acting monoclonal antibody for preventing respiratory syncytial virus (RSV) infection in newborns and infants, allowing for a single dose to protect throughout the RSV season, which is a significant improvement over the monthly injections required for the existing treatment, palivizumab.

The drug works by targeting a specific site on the RSV fusion protein and has shown positive results in Phase 2b and 3 clinical trials, indicating its efficacy and potential to reduce hospitalizations and mortality associated with RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirsevimab: review of pharmacology, antiviral activity and emerging clinical experience for respiratory syncytial virus infection in infants. Jorgensen, SCJ.[2023]

The BVAC-B immunotherapy, tested in eight patients with HER2-positive advanced gastric cancer, showed a safe toxicity profile with no dose-limiting toxicities, although treatment-related adverse events like fever were noted at medium and high doses.

While BVAC-B demonstrated limited clinical activity, it successfully activated immune responses in patients, suggesting that earlier intervention or combination therapies may enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase 1 Study of a B Cell- and Monocyte-Based Immunotherapeutic Vaccine Against HER2-Positive Advanced Gastric Cancer. Jung, M., Lee, JB., Kim, HS., et al.[2023]

The novel PD-1 B-cell peptide vaccine (PD1-Vaxx) demonstrated superior efficacy compared to standard anti-PD-1 monoclonal antibodies in preclinical mouse models of colon carcinoma, suggesting it may be a promising alternative for cancer treatment.

Combining PD1-Vaxx with a HER-2 peptide vaccine resulted in enhanced tumor growth inhibition, and both vaccines showed a favorable safety profile with no observed toxicity or autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. Kaumaya, PTP., Guo, L., Overholser, J., et al.[2021]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

The abstract lists a wide range of medical interventions and drugs, indicating a comprehensive review of various treatments, but does not provide specific efficacy or safety data for any individual treatment.

The mention of numerous drugs and therapies suggests a focus on exploring diverse therapeutic options, but without detailed results or conclusions, the effectiveness or mechanisms of action remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. Tomillero, A., Moral, MA.[2008]

In a study of 75 non-small cell lung cancer patients treated with nivolumab, 43% experienced immune-related adverse events (irAEs), primarily affecting the skin, lungs, and gastrointestinal system, with most being of moderate severity.

Patients who developed irAEs had significantly better treatment outcomes, with a median progression-free survival of 9.49 months compared to 1.99 months for those without irAEs, indicating that these adverse events may serve as strong predictors of treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of immune-mediated reactions in patients with non-small cell lung cancer treated with nivolumab and its association with effectiveness. Cortijo-Cascajares, S., Cercós-Lletí, AC., Ortiz-Pérez, S., et al.[2023]

Tocilizumab demonstrated a clinical benefit in 85% of cancer patients treated for immune-related adverse events (irAEs) associated with immune checkpoint inhibitors, with no cases of disease progression reported during treatment.

The study suggests that tocilizumab can be safely continued alongside immune checkpoint inhibitors in managing irAEs, allowing for effective treatment without compromising cancer therapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for the treatment of immune-related adverse events: a systematic literature review and a multicentre case series. Campochiaro, C., Farina, N., Tomelleri, A., et al.[2021]

In a postmarketing surveillance study of 3601 Japanese patients with advanced non-small-cell lung cancer treated with nivolumab, the treatment-related adverse events occurred in 47.1% of patients, with 15.9% experiencing grade 3 or higher events, indicating a manageable safety profile similar to clinical trials.

The most common adverse events included interstitial lung disease (6.4%), hypothyroidism (5.7%), and diarrhea (4.4%), with specific risk factors identified for these events, suggesting that careful monitoring is needed for patients with certain pre-existing conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety of nivolumab in patients with non-small-cell lung cancer in Japan: Postmarketing surveillance. Yamamoto, N., Nakanishi, Y., Gemma, A., et al.[2021]

Rituximab-treated patients with B cell non-Hodgkin lymphoma (NHL) showed significant humoral immunodeficiency, with only 20% responding to diphtheria and pneumococcal vaccinations, despite having relatively normal IgG levels.

Subcutaneous immunoglobulin (subq Ig) therapy was well-tolerated and significantly increased serum IgG levels, leading to a reduction in nonneutropenic infections, indicating its efficacy as a supportive treatment for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of 20% Subcutaneous Immunoglobulin Replacement Therapy in Patients With B Cell Non-Hodgkin Lymphoma With Humoral Immune Dysfunction After Treatment With Rituximab. Mustafa, SS., Jamshed, S., Vadamalai, K., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Nirsevimab: review of pharmacology, antiviral activity and emerging clinical experience for respiratory syncytial virus infection in infants. [2023]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

First-in-Human Phase 1 Study of a B Cell- and Monocyte-Based Immunotherapeutic Vaccine Against HER2-Positive Advanced Gastric Cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. [2008]

6. England pubmed.ncbi.nlm.nih.gov

Analysis of immune-mediated reactions in patients with non-small cell lung cancer treated with nivolumab and its association with effectiveness. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Tocilizumab for the treatment of immune-related adverse events: a systematic literature review and a multicentre case series. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Real-world safety of nivolumab in patients with non-small-cell lung cancer in Japan: Postmarketing surveillance. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

The Use of 20% Subcutaneous Immunoglobulin Replacement Therapy in Patients With B Cell Non-Hodgkin Lymphoma With Humoral Immune Dysfunction After Treatment With Rituximab. [2021]