A Phase 1/2A, Randomized Study of a T Follicular Helper (TFH)-Targeting Genetic Vaccine Strategy Designed to Induce Broad, Durable Immune Responses
CONTENDER
2 other identifiers
interventional
80
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 covid19
Started Oct 2025
Longer than P75 for phase_1 covid19
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 9, 2024
CompletedFirst Posted
Study publicly available on registry
February 6, 2025
CompletedStudy Start
First participant enrolled
October 21, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2029
October 31, 2025
July 1, 2025
2.1 years
October 9, 2024
October 29, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (9)
Frequency of solicited local reactogenicity adverse events (AEs) within 7 days after dosing.
Number of participants with solicited local reactogenicity AEs (injection site pain, erythema, or swelling) within 7 days after dosing. An AE is any untoward medical occurrence in a clinical investigation of a patient administered a pharmaceutical product and that does not necessarily have a causal relationship with the treatment.
7 days
Frequency of solicited systemic reactogenicity AEs within 7 days after dosing.
Number of participants with solicited systemic reactogenicity AEs (malaise, participant-measured body temperature, fatigue, headache, chills, nausea, muscle aches/pain, joint pain) within 7 days after dosing.
7 days
Frequency of unsolicited AEs within 28 days after dosing.
Number of participants with unsolicited AEs within 28 days after dosing. Unsolicited AEs are AEs that were not pre-defined as solicited.
28 days
Frequency of serious adverse events (SAEs) within 28 days after dosing.
Number of participants with an SAE within 28 days after dosing. An SAE is defined as any adverse event that results in any of the following outcomes: death during a period of surveillance defined by the protocol, a life-threatening adverse experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. The following are also considered SAEs for this study: severe COVID-19, defined as COVID-19 requiring hospitalization or supplemental oxygen, myocarditis or pericarditis within 6 weeks of study vaccination, and acute or new onset thrombosis or thromboembolism within 60 days of vaccination.
28 days
Frequency of adverse events of special interest (AESIs) within 28 days after dosing.
Number of participants with AESIs. AESIs defined as: thrombotic or thromboembolic events, thrombosis with thrombocytopenia syndrome, immune thrombocytopenia, or capillary leak syndrome occurring within 60 days; new thrombocytopenia \<150 x 10\^9/L or below the lower laboratory limit of normal or worsening in grade of thrombocytopenia within 60 days after study vaccination; new D-dimer elevation \>2000 ng/mL within 60 days; laryngospasm, bronchospasm, or anaphylaxis assessed as at least possibly related; generalized urticaria assessed as related; any other grade allergic/ hypersensitivity reaction within 7 days; any ulceration, abscess, or necrosis at injection site assessed as possibly related; myocarditis or pericarditis occurring within 6 weeks; new diagnosis of Guillain-Barré syndrome occurring within 60 days; any new or worsened immune mediated medical condition; grade 3+ lab abnormality for which there is a reasonable possibility of causal relationship to study treatment.
28 days
Frequency of medically attended adverse events (MAAEs) within 28 days after dosing.
Number of participants with MAAEs (MAAE defined as an AE resulting in a hospitalization, emergency room visit, or otherwise unscheduled visit with medical personnel for any reason) within 28 days after dosing.
28 days
Geometric mean titers (GMTs) of serum anti-XBB.1.5 neutralizing antibodies (NAb) through week 8.
Serum anti-XBB.1.5 NAb GMT
8 weeks
Proportion of participants achieving serum anti-XBB.1.5 NAb titers of 1:250 or better through week 8.
Proportion of participants achieving serum anti-XBB.1.5 NAb titers of 1:250 or better
8 weeks
Geometric mean fold rise (GMFR) from pre-dose to week 8 in serum anti-XBB.1.5 NAb responses.
Geometric mean fold rise (GMFR) in serum anti-XBB.1.5 NAb levels
Pre-dose to 8 weeks
Secondary Outcomes (48)
Serum anti-D614G NAb GMTs through week 8.
8 weeks
Serum anti-JN.1* NAb GMTs through week 8.
8 weeks
Proportion of participants achieving anti-D614G NAb titers of 1:250 or better through week 8.
8 weeks
Proportion of participants achieving anti-JN.1* NAb titers of 1:250 or better through week 8.
8 weeks
GMFR from pre-dose to week 8 in serum anti-D614G NAb responses.
Pre-dose to 8 weeks
- +43 more secondary outcomes
Study Arms (16)
Dose Cohort 1, Arm 1A
EXPERIMENTALIntervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^6 vp (0.5mL) IM once
Dose Cohort 1, Arm 1B
EXPERIMENTALIntervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^6 vp (0.5mL) IM once
Dose Cohort 2, Arm 2A
EXPERIMENTALIntervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^7 vp (0.5mL) IM once
Dose Cohort 2, Arm 2B
EXPERIMENTALIntervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^7 vp (0.5mL) IM once
Dose Cohort 3, Arm 3A
EXPERIMENTALIntervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^8 vp (0.5mL) IM once
Dose Cohort 3, Arm 3B
EXPERIMENTALIntervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^8 vp (0.5mL) IM once
Dose Cohort 4, Arm 4A
EXPERIMENTALIntervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^9 vp (0.5mL) IM once
Dose Cohort 4, Arm 4B
EXPERIMENTALIntervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^9 vp (0.5mL) IM once
Dose Cohort 5, Arm 5A
EXPERIMENTALIntervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^10 vp (0.5mL) IM once
Dose Cohort 5, Arm 5B
EXPERIMENTALIntervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^10 vp (0.5mL) IM once
Dose Cohort 6, Arm 6A
EXPERIMENTALIntervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^9 vp (0.5mL) IM once
Dose Cohort 6, Arm 6B
EXPERIMENTALIntervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^9 vp (0.5mL) IM once
Dose Cohort 6, Arm 6C
PLACEBO COMPARATORIntervention: Placebo (normal saline) Dose: 0.5mL IM once
Dose Cohort 7, Arm 7A
EXPERIMENTALIntervention: CoTend-s3BXBB (SARS2-17032) Dose: 1x10\^10 vp (0.5mL) IM once
Dose Cohort 7, Arm 7B
EXPERIMENTALIntervention: CoTend-BXBB (SARS2-30404) Dose: 1x10\^10 vp (0.5mL) IM once
Dose Cohort 7, Arm 7C
PLACEBO COMPARATORIntervention: Placebo (normal saline) Dose: 0.5mL IM once
Interventions
Ad35-vectored SARS-CoV-2 RBD (XBB.1.5) vaccine
Ad35-vectored s3-SARS-CoV-2 RBD (XBB.1.5) vaccine
Sterile sodium chloride 0.9% for injection, preservative free
Eligibility Criteria
You may qualify if:
- Individuals 40 - 64 years of age
- Received at least two doses of a COVID-19 mRNA vaccine (Moderna or Pfizer) \> 120 days before study entry
- Nasal SARS-CoV-2 negative by molecular (polymerase chain reaction, PCR) testing at screening
- The following laboratory criteria must be met at screening:
- Total white blood cell (WBC) count \> 3500 cells/mm3
- Absolute neutrophil count (ANC) \> 1500 cells/mm3
- Hemoglobin \> 13.5 g/dL if male sex and \> 12.0 g/dL if female sex
- Platelet count \> 140,000/uL
- Estimated creatinine clearance (CrCl) \> 50 mL/min by Cockroft-Gault equation
- Total bilirubin ≤ 1.1x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 1.3x ULN
- Alanine aminotransferase (ALT) ≤ 1.3x ULN
- 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
- +2 more criteria
You may not qualify if:
- Participants are excluded from the study if any of the following criteria are met:
- Pregnant or breastfeeding
- 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:
- Condoms (male or female) with or without a spermicidal agent
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD)
- Hormone-based contraceptive such as oral birth control pills
- 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
- Plan to receive a non-study SARS-CoV-2 vaccine within 8 weeks after study entry
- HIV infection
- Hepatitis B core antibody or hepatitis B surface antigen positive at screening
- 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.
- History of cirrhotic liver disease
- 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
- History of or active autoimmune disease that has required systemic immunosuppressive or immunomodulatory therapy
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Kara Chewlead
- University of California, San Franciscocollaborator
- University of California, Daviscollaborator
- Tendel Therapies, Inc.collaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
Study Sites (2)
UCLA Westwood
Los Angeles, California, 90095, United States
UCSF Community and Clinical Research Center
San Francisco, California, 94110, United States
Related Publications (11)
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.
PMID: 36356052BACKGROUNDDe 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.
PMID: 28878083BACKGROUNDWang Q, Iketani S, Li Z, Liu L, Guo Y, Huang Y, Bowen AD, Liu M, Wang M, Yu J, Valdez R, Lauring AS, Sheng Z, Wang HH, Gordon A, Liu L, Ho DD. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell. 2023 Jan 19;186(2):279-286.e8. doi: 10.1016/j.cell.2022.12.018. Epub 2022 Dec 14.
PMID: 36580913BACKGROUNDHavervall S, Marking U, Svensson J, Greilert-Norin N, Bacchus P, Nilsson P, Hober S, Gordon M, Blom K, Klingstrom J, Aberg M, Smed-Sorensen A, Thalin C. Anti-Spike Mucosal IgA Protection against SARS-CoV-2 Omicron Infection. N Engl J Med. 2022 Oct 6;387(14):1333-1336. doi: 10.1056/NEJMc2209651. Epub 2022 Sep 14. No abstract available.
PMID: 36103621BACKGROUNDBalachandran 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.
PMID: 35090598BACKGROUNDFuchs 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.
PMID: 26587311BACKGROUNDNwanegbo 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.
PMID: 15013987BACKGROUNDQu 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.
PMID: 36069925BACKGROUNDGilboa M, Regev-Yochay G, Mandelboim M, Indenbaum V, Asraf K, Fluss R, Amit S, Mendelson E, Doolman R, Afek A, Freedman LS, Kreiss Y, Lustig Y. Durability of Immune Response After COVID-19 Booster Vaccination and Association With COVID-19 Omicron Infection. JAMA Netw Open. 2022 Sep 1;5(9):e2231778. doi: 10.1001/jamanetworkopen.2022.31778.
PMID: 36107426BACKGROUNDChen Y, Tong P, Whiteman NB, et al. Differential antibody dynamics to SARS-CoV-2 infection and vaccination. bioRxiv 2021:2021.09.09.459504.
BACKGROUNDPlanas 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.
PMID: 34237773BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kara Chew, MD, MS
University of California, Los Angeles
- PRINCIPAL INVESTIGATOR
Steven Deeks, MD
University of California, San Francisco
- PRINCIPAL INVESTIGATOR
Dennis Hartigan-O'Connor, MD, PhD
University of California, Davis
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Associate Professor of Medicine
Study Record Dates
First Submitted
October 9, 2024
First Posted
February 6, 2025
Study Start
October 21, 2025
Primary Completion (Estimated)
December 1, 2027
Study Completion (Estimated)
October 1, 2029
Last Updated
October 31, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- After completion of the study analyses and publications.
- Access Criteria
- There will be a managed access process with requirement of a data use agreement.
De-identified data.