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

NCT ID: NCT06810934

Last Updated: 2025-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-21

Study Completion Date

2029-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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COVID-19 SARS-CoV-2 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Dose Cohort 1, Arm 1A

Intervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^6 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-s3BXBB (SARS2-17032)

Intervention Type BIOLOGICAL

Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 1, Arm 1B

Intervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^6 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-BXBB (SARS2-30404)

Intervention Type BIOLOGICAL

Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 2, Arm 2A

Intervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^7 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-s3BXBB (SARS2-17032)

Intervention Type BIOLOGICAL

Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 2, Arm 2B

Intervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^7 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-BXBB (SARS2-30404)

Intervention Type BIOLOGICAL

Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 3, Arm 3A

Intervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^8 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-s3BXBB (SARS2-17032)

Intervention Type BIOLOGICAL

Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 3, Arm 3B

Intervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^8 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-BXBB (SARS2-30404)

Intervention Type BIOLOGICAL

Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 4, Arm 4A

Intervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^9 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-s3BXBB (SARS2-17032)

Intervention Type BIOLOGICAL

Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 4, Arm 4B

Intervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^9 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-BXBB (SARS2-30404)

Intervention Type BIOLOGICAL

Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 5, Arm 5A

Intervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^10 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-s3BXBB (SARS2-17032)

Intervention Type BIOLOGICAL

Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 5, Arm 5B

Intervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^10 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-BXBB (SARS2-30404)

Intervention Type BIOLOGICAL

Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 6, Arm 6A

Intervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^9 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-s3BXBB (SARS2-17032)

Intervention Type BIOLOGICAL

Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 6, Arm 6B

Intervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^9 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-BXBB (SARS2-30404)

Intervention Type BIOLOGICAL

Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 6, Arm 6C

Intervention: Placebo (normal saline) Dose: 0.5mL IM once

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Sterile sodium chloride 0.9% for injection, preservative free

Dose Cohort 7, Arm 7A

Intervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^10 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-s3BXBB (SARS2-17032)

Intervention Type BIOLOGICAL

Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 7, Arm 7B

Intervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^10 vp (0.5mL) IM once

Group Type EXPERIMENTAL

CoTend-BXBB (SARS2-30404)

Intervention Type BIOLOGICAL

Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine

Dose Cohort 7, Arm 7C

Intervention: Placebo (normal saline) Dose: 0.5mL IM once

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Sterile sodium chloride 0.9% for injection, preservative free

Interventions

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CoTend-BXBB (SARS2-30404)

Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine

Intervention Type BIOLOGICAL

CoTend-s3BXBB (SARS2-17032)

Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine

Intervention Type BIOLOGICAL

Placebo

Sterile sodium chloride 0.9% for injection, preservative free

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion 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.

Reproductive potential is defined as:
* 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

Exclusion Criteria

Participants are excluded from the study if any of the following criteria are met:

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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of California, San Francisco

OTHER

Sponsor Role collaborator

University of California, Davis

OTHER

Sponsor Role collaborator

Tendel Therapies, Inc.

UNKNOWN

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Kara Chew

OTHER

Sponsor Role lead

Responsible Party

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Kara Chew

Associate Professor of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Kara Chew, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Steven Deeks, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Dennis Hartigan-O'Connor, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

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UCLA Westwood

Los Angeles, California, United States

Site Status RECRUITING

UCSF Community and Clinical Research Center

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Kara Chew, MD, MS

Role: CONTACT

310-825-0796

Stephanie Buchbinder, MPH

Role: CONTACT

310-825-5147

Facility Contacts

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Kevin Pizarro

Role: primary

310-843-2015

Marin Ewing

Role: primary

415-353-9599

References

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Bowen JE, Park YJ, Stewart C, Brown JT, Sharkey WK, Walls AC, Joshi A, Sprouse KR, McCallum M, Tortorici MA, Franko NM, Logue JK, Mazzitelli IG, Nguyen AW, Silva RP, Huang Y, Low JS, Jerak J, Tiles SW, Ahmed K, Shariq A, Dan JM, Zhang Z, Weiskopf D, Sette A, Snell G, Posavad CM, Iqbal NT, Geffner J, Bandera A, Gori A, Sallusto F, Maynard JA, Crotty S, Van Voorhis WC, Simmerling C, Grifantini R, Chu HY, Corti D, Veesler D. SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines. Sci Immunol. 2022 Dec 23;7(78):eadf1421. doi: 10.1126/sciimmunol.adf1421. Epub 2022 Dec 23.

Reference Type BACKGROUND
PMID: 36356052 (View on PubMed)

De Boer RJ, Perelson AS. How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response. J Virol. 2017 Oct 27;91(22):e00983-17. doi: 10.1128/JVI.00983-17. Print 2017 Nov 15.

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PMID: 28878083 (View on PubMed)

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Balachandran H, Phetsouphanh C, Agapiou D, Adhikari A, Rodrigo C, Hammoud M, Shrestha LB, Keoshkerian E, Gupta M, Turville S, Christ D, King C, Sasson SC, Bartlett A, Grubor-Bauk B, Rawlinson W, Aggarwal A, Stella AO, Klemm V, Mina MM, Post JJ, Hudson B, Gilroy N, Konecny P, Ahlenstiel G, Dwyer DE, Sorrell TC, Kelleher A, Tedla N, Lloyd AR, Martinello M, Bull RA; COSIN Study Group. Maintenance of broad neutralizing antibodies and memory B cells 1 year post-infection is predicted by SARS-CoV-2-specific CD4+ T cell responses. Cell Rep. 2022 Feb 8;38(6):110345. doi: 10.1016/j.celrep.2022.110345. Epub 2022 Jan 19.

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Fuchs JD, Bart PA, Frahm N, Morgan C, Gilbert PB, Kochar N, DeRosa SC, Tomaras GD, Wagner TM, Baden LR, Koblin BA, Rouphael NG, Kalams SA, Keefer MC, Goepfert PA, Sobieszczyk ME, Mayer KH, Swann E, Liao HX, Haynes BF, Graham BS, McElrath MJ; NIAID HIV Vaccine Trials Network. Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals. J AIDS Clin Res. 2015 May;6(5):461. doi: 10.4172/2155-6113.1000461. Epub 2015 May 23.

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Nwanegbo E, Vardas E, Gao W, Whittle H, Sun H, Rowe D, Robbins PD, Gambotto A. Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States. Clin Diagn Lab Immunol. 2004 Mar;11(2):351-7. doi: 10.1128/cdli.11.2.351-357.2004.

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Qu P, Faraone JN, Evans JP, Zheng YM, Yu L, Ma Q, Carlin C, Lozanski G, Saif LJ, Oltz EM, Gumina RJ, Liu SL. Durability of Booster mRNA Vaccine against SARS-CoV-2 BA.2.12.1, BA.4, and BA.5 Subvariants. N Engl J Med. 2022 Oct 6;387(14):1329-1331. doi: 10.1056/NEJMc2210546. Epub 2022 Sep 7. No abstract available.

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Planas D, Veyer D, Baidaliuk A, Staropoli I, Guivel-Benhassine F, Rajah MM, Planchais C, Porrot F, Robillard N, Puech J, Prot M, Gallais F, Gantner P, Velay A, Le Guen J, Kassis-Chikhani N, Edriss D, Belec L, Seve A, Courtellemont L, Pere H, Hocqueloux L, Fafi-Kremer S, Prazuck T, Mouquet H, Bruel T, Simon-Loriere E, Rey FA, Schwartz O. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 2021 Aug;596(7871):276-280. doi: 10.1038/s41586-021-03777-9. Epub 2021 Jul 8.

Reference Type BACKGROUND
PMID: 34237773 (View on PubMed)

Other Identifiers

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1U01AI172800-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-001884

Identifier Type: -

Identifier Source: org_study_id

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