RECRUITING

A Phase 1/2A, Randomized Study of a T Follicular Helper (TFH)-Targeting Genetic Vaccine Strategy Designed to Induce Broad, Durable Immune Responses

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The goal of this clinical trial is to test two investigational COVID-19 booster vaccines, called CoTend-s3BXBB and CoTend-BXBB, in healthy volunteers ages 40-64. The CoTend-s3BXBB vaccine includes a component called "s3", which was designed to improve the body's response to the vaccine. CoTend-BXBB is the same vaccine without s3. The main questions the study aims to answer are: 1) Is the investigational vaccine safe? 2) Does "s3" lead to bigger, broader, and longer-lasting responses to the vaccine? 5 different doses of the vaccines will be studied. Participants will receive a single dose of either CoTend-s3BXBB, CoTend-BXBB, or placebo. Participants will be monitored for side effects. Saliva, nasal, and blood samples will be collected and immune responses to the vaccine will be measured.

Official Title

A Phase 1/2A, Randomized Study of a T Follicular Helper (TFH)-Targeting Genetic Vaccine Strategy Designed to Induce Broad, Durable Immune Responses

Quick Facts

Study Start:2025-09-01

Study Completion:2029-08-14

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06810934

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:40 Years to 64 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
1. Individuals 40 - 64 years of age 2. Received at least two doses of a COVID-19 mRNA vaccine (Moderna or Pfizer) \> 120 days before study entry 3. Nasal SARS-CoV-2 negative by molecular (polymerase chain reaction, PCR) testing at screening 4. The following laboratory criteria must be met at screening: 1. Total white blood cell (WBC) count \> 3500 cells/mm3 2. Absolute neutrophil count (ANC) \> 1500 cells/mm3 3. Hemoglobin \> 13.5 g/dL if male sex and \> 12.0 g/dL if female sex 4. Platelet count \> 140,000/uL 5. Estimated creatinine clearance (CrCl) \> 50 mL/min by Cockroft-Gault equation 6. Total bilirubin ≤ 1.1x upper limit of normal (ULN) 7. Aspartate aminotransferase (AST) ≤ 1.3x ULN 8. Alanine aminotransferase (ALT) ≤ 1.3x ULN 5. Individuals of reproductive potential must have a negative serum or urine beta-human chorionic gonadotropin (ß-HCG) test at screening and within 48 hours prior to entry. * Participants who have reached menarche * Participants who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available * Participants who have not undergone surgical contraception (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or bilateral salpingectomy) NOTE: Participants who have undergone bilateral tubal ligation within the 24 weeks prior to screening are considered to be of reproductive potential and, if participating in sexual activity that could lead to pregnancy, contraception is required as per 5.2.2 exclusion criterion 2. 6. Able and willing to provide informed consent	1. Pregnant or breastfeeding 2. For participants capable of becoming pregnant and engaging in sexual activity that can lead to pregnancy, unwillingness to use contraception during participation in the study. For participants capable of becoming pregnant, two of the following forms of contraception are required through 30 days following administration of study intervention, one of which must be a barrier method: 1. Condoms (male or female) with or without a spermicidal agent 2. Diaphragm or cervical cap with spermicide 3. Intrauterine device (IUD) 4. Hormone-based contraceptive such as oral birth control pills 3. Known close contact with anyone with confirmed SARS-CoV-2 infection (defined as positive SARS-CoV-2 nucleic acid or antigen testing by laboratory-based or home self-test) within 2 weeks prior to expected study entry 4. Plan to receive a non-study SARS-CoV-2 vaccine within 8 weeks after study entry 5. HIV infection 6. Hepatitis B core antibody or hepatitis B surface antigen positive at screening 7. Current active hepatitis C. Participants must be hepatitis C virus (HCV) antibody negative or have evidence of cleared HCV infection. If the participant is HCV antibody positive or indeterminate, an unquantifiable HCV RNA result (below lower limit of quantification, either target detected or target not detected) within 42 days prior to study entry is required. Those who are currently receiving HCV antiviral therapy or those who have received HCV treatment in the last 3 months prior to study entry will be excluded. 8. History of cirrhotic liver disease 9. History of thrombosis with thrombocytopenia syndrome (TTS), immune thrombocytopenia, thromboembolic events, capillary leak syndrome, other thrombotic disease or known increased risk of thrombosis due to genetic disorders or malignancy 10. History of or active autoimmune disease that has required systemic immunosuppressive or immunomodulatory therapy 11. History of myocarditis, pericarditis, or myopericarditis 12. Potential myocarditis or pericarditis identified at screening, defined as high-sensitivity troponin I (hsTnI) \> ULN or 12-lead ECG compatible with pericarditis WITH compatible symptoms (regardless of troponin I level) at screening 13. History of Guillain-Barré syndrome 14. History of coagulopathy or bleeding disorder considered a contraindication to intramuscular injection or phlebotomy 15. Symptomatic acute or chronic illness requiring ongoing medical or surgical care, including requirement for new medications, in the past 3 months. Transient illnesses or injuries that are resolved prior to screening are not exclusionary. Minor adjustments in stable therapy for chronic conditions such as hypertension are not exclusionary. Use of over-the-counter medications for any acute or chronic illness is also not exclusionary. 16. Serious medical or psychiatric illness that, in the opinion of the site investigator, would interfere with the ability to adhere to study requirements or to give informed consent 17. Treatment with systemic immunosuppressive or immunomodulatory drugs, and/or exposure to any immunosuppressive/immunomodulatory drug in the 30 days prior to study entry (e.g. corticosteroid therapy equal to or exceeding a dose of 20 mg/day of prednisone for more than 10 days, interleukins, interferons, methotrexate, rituximab, and cancer chemotherapy). Use of topical, inhaled, intra-articular, or nasal steroid use is not exclusionary. 18. Active malignancy or history of malignancy within the 4 years prior to study entry. Non-melanoma skin cancers (such as basal or squamous cell skin cancers) and non-invasive cervical or anal intraepithelial lesions are not exclusionary. 19. History of solid organ or hematopoietic stem cell transplantation 20. History of primary immunodeficiency disorder 21. Ongoing complications or morbidity associated with prior diagnoses of malignancies requiring continued medical or surgical intervention. Chronic stable complications or morbidity not requiring new medications or other medical or surgical intervention in the past 3 months are not exclusionary. 22. Administration or planned administration of blood products or licensed non-SARS-CoV-2 vaccines \<14 days prior to or within 14 days after study entry 23. Receipt of any antibody-based therapy (investigational or approved) for prophylaxis or treatment of COVID-19 in the preceding 6 months 24. Receipt of immunoglobulin therapy in the year prior to study entry or scheduled or anticipated immunoglobulin administration during the study period. 25. Prior receipt of any non-mRNA SARS-CoV-2 vaccine 26. Receipt of any SARS-CoV-2 vaccination in the 120 days prior to study entry 27. Documented SARS-CoV-2 infection in the 120 days prior to study entry 28. History of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention (medications requiring a prescription or surgical intervention) after receipt of a vaccine or intervention that includes one or more of the same components contained in the study product 29. Have participated in an interventional clinical study within 28 days prior to screening (based on medical history interview) or plans to do so while participating in this study 30. Any clinical concerns as determined by the investigator that might affect the potential participant's safety in the study.

Inclusion Criteria

Exclusion Criteria

1. Individuals 40 - 64 years of age
2. Received at least two doses of a COVID-19 mRNA vaccine (Moderna or Pfizer) \> 120 days before study entry
3. Nasal SARS-CoV-2 negative by molecular (polymerase chain reaction, PCR) testing at screening
4. The following laboratory criteria must be met at screening:
1. Total white blood cell (WBC) count \> 3500 cells/mm3
2. Absolute neutrophil count (ANC) \> 1500 cells/mm3
3. Hemoglobin \> 13.5 g/dL if male sex and \> 12.0 g/dL if female sex
4. Platelet count \> 140,000/uL
5. Estimated creatinine clearance (CrCl) \> 50 mL/min by Cockroft-Gault equation
6. Total bilirubin ≤ 1.1x upper limit of normal (ULN)
7. Aspartate aminotransferase (AST) ≤ 1.3x ULN
8. Alanine aminotransferase (ALT) ≤ 1.3x ULN
5. Individuals of reproductive potential must have a negative serum or urine beta-human chorionic gonadotropin (ß-HCG) test at screening and within 48 hours prior to entry.
* Participants who have reached menarche
* Participants who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available
* Participants who have not undergone surgical contraception (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or bilateral salpingectomy) NOTE: Participants who have undergone bilateral tubal ligation within the 24 weeks prior to screening are considered to be of reproductive potential and, if participating in sexual activity that could lead to pregnancy, contraception is required as per 5.2.2 exclusion criterion 2.
6. Able and willing to provide informed consent

1. Pregnant or breastfeeding
2. For participants capable of becoming pregnant and engaging in sexual activity that can lead to pregnancy, unwillingness to use contraception during participation in the study. For participants capable of becoming pregnant, two of the following forms of contraception are required through 30 days following administration of study intervention, one of which must be a barrier method:
1. Condoms (male or female) with or without a spermicidal agent
2. Diaphragm or cervical cap with spermicide
3. Intrauterine device (IUD)
4. Hormone-based contraceptive such as oral birth control pills
3. Known close contact with anyone with confirmed SARS-CoV-2 infection (defined as positive SARS-CoV-2 nucleic acid or antigen testing by laboratory-based or home self-test) within 2 weeks prior to expected study entry
4. Plan to receive a non-study SARS-CoV-2 vaccine within 8 weeks after study entry
5. HIV infection
6. Hepatitis B core antibody or hepatitis B surface antigen positive at screening
7. Current active hepatitis C. Participants must be hepatitis C virus (HCV) antibody negative or have evidence of cleared HCV infection. If the participant is HCV antibody positive or indeterminate, an unquantifiable HCV RNA result (below lower limit of quantification, either target detected or target not detected) within 42 days prior to study entry is required. Those who are currently receiving HCV antiviral therapy or those who have received HCV treatment in the last 3 months prior to study entry will be excluded.
8. History of cirrhotic liver disease
9. History of thrombosis with thrombocytopenia syndrome (TTS), immune thrombocytopenia, thromboembolic events, capillary leak syndrome, other thrombotic disease or known increased risk of thrombosis due to genetic disorders or malignancy
10. History of or active autoimmune disease that has required systemic immunosuppressive or immunomodulatory therapy
11. History of myocarditis, pericarditis, or myopericarditis
12. Potential myocarditis or pericarditis identified at screening, defined as high-sensitivity troponin I (hsTnI) \> ULN or 12-lead ECG compatible with pericarditis WITH compatible symptoms (regardless of troponin I level) at screening
13. History of Guillain-Barré syndrome
14. History of coagulopathy or bleeding disorder considered a contraindication to intramuscular injection or phlebotomy
15. Symptomatic acute or chronic illness requiring ongoing medical or surgical care, including requirement for new medications, in the past 3 months. Transient illnesses or injuries that are resolved prior to screening are not exclusionary. Minor adjustments in stable therapy for chronic conditions such as hypertension are not exclusionary. Use of over-the-counter medications for any acute or chronic illness is also not exclusionary.
16. Serious medical or psychiatric illness that, in the opinion of the site investigator, would interfere with the ability to adhere to study requirements or to give informed consent
17. Treatment with systemic immunosuppressive or immunomodulatory drugs, and/or exposure to any immunosuppressive/immunomodulatory drug in the 30 days prior to study entry (e.g. corticosteroid therapy equal to or exceeding a dose of 20 mg/day of prednisone for more than 10 days, interleukins, interferons, methotrexate, rituximab, and cancer chemotherapy). Use of topical, inhaled, intra-articular, or nasal steroid use is not exclusionary.
18. Active malignancy or history of malignancy within the 4 years prior to study entry. Non-melanoma skin cancers (such as basal or squamous cell skin cancers) and non-invasive cervical or anal intraepithelial lesions are not exclusionary.
19. History of solid organ or hematopoietic stem cell transplantation
20. History of primary immunodeficiency disorder
21. Ongoing complications or morbidity associated with prior diagnoses of malignancies requiring continued medical or surgical intervention. Chronic stable complications or morbidity not requiring new medications or other medical or surgical intervention in the past 3 months are not exclusionary.
22. Administration or planned administration of blood products or licensed non-SARS-CoV-2 vaccines \<14 days prior to or within 14 days after study entry
23. Receipt of any antibody-based therapy (investigational or approved) for prophylaxis or treatment of COVID-19 in the preceding 6 months
24. Receipt of immunoglobulin therapy in the year prior to study entry or scheduled or anticipated immunoglobulin administration during the study period.
25. Prior receipt of any non-mRNA SARS-CoV-2 vaccine
26. Receipt of any SARS-CoV-2 vaccination in the 120 days prior to study entry
27. Documented SARS-CoV-2 infection in the 120 days prior to study entry
28. History of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention (medications requiring a prescription or surgical intervention) after receipt of a vaccine or intervention that includes one or more of the same components contained in the study product
29. Have participated in an interventional clinical study within 28 days prior to screening (based on medical history interview) or plans to do so while participating in this study
30. Any clinical concerns as determined by the investigator that might affect the potential participant's safety in the study.

Contacts and Locations

Study Contact

Kara Chew, MD, MS

CONTACT

310-825-0796

kchew@mednet.ucla.edu

Stephanie Buchbinder, MPH

CONTACT

310-825-5147

SBuchbinder@mednet.ucla.edu

Principal Investigator

Kara Chew, MD, MS

PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Steven Deeks, MD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Dennis Hartigan-O'Connor, MD, PhD

PRINCIPAL_INVESTIGATOR

University of California, Davis

Study Locations (Sites)

UCLA Westwood

Los Angeles, California, 90095

United States

Collaborators and Investigators

Sponsor: Kara Chew

Kara Chew, MD, MS, PRINCIPAL_INVESTIGATOR, University of California, Los Angeles
Steven Deeks, MD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco
Dennis Hartigan-O'Connor, MD, PhD, PRINCIPAL_INVESTIGATOR, University of California, Davis

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-09-01

Study Completion Date2029-08-14

Study Record Updates

Study Start Date2025-09-01

Study Completion Date2029-08-14

Terms related to this study

Keywords Provided by Researchers

COVID-19
vaccine
SARS-CoV-2

Additional Relevant MeSH Terms

COVID-19