Evaluation of Safety and Immunogenicity of Ad26.Mos4.HIV and CH505 TF chTrimer Combination in Healthy Adults

NCT06205056 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: S-22-03W81XWH-18-2-0040
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, randomized, double-blind, placebo-controlled clinical study to define the safety and immunogenicity resulting from a rapid dose-escalating vaccination schedule as compared to that of a co-administered, dose-consistent vaccination schedule. Participants randomized to receive vaccines will get either dose-consistent injections of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV or rapid, dose-escalating injections of CH505 TF chTrimer+ALFQ with an Ad26.Mos4.HIV prime, followed by dose-consistent injection of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV

Conditions

Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (4)

• Occurrence and severity of solicited local and systemic adverse events (AEs) following candidate vaccine administration

  Occurrence and severity of solicited local and systemic adverse events (AEs) following candidate vaccine administration.

  Day 0 - Day 505

• Occurrence, severity, and relationship to vaccination of unsolicited adverse events after candidate vaccine administration

  Occurrence, severity, and relationship to vaccination of unsolicited adverse events after candidate vaccine administration.

  Day 0 - Day 505

• Occurrence of serious adverse events (SAEs) following candidate vaccine administration

  Occurrence of serious adverse events (SAEs) following candidate vaccine administration.

  Day 0 - Day 505

• Occurrence of adverse events of special interest (AESIs) following candidate vaccine administration

  Occurrence of adverse events of special interest (AESIs) following candidate vaccine administration.

  Day 0 - Day 505

Secondary Outcomes (2)

• Quantify IgG binding antibodies to HIV Env in terms of magnitude, breadth, and durability between Arms

  Visit Days 1, 4, 8, 15, 29, 57, 71, 85,169, 183, and 337

• Quantify neutralizing antibodies to HIV Env in terms of magnitude, breadth, and durability between Arms

  Visit Days 1, 4, 8, 15, 29, 57, 71, 85,169, 183, and 337

Other Outcomes (4)

• Characterize binding antibody Fc engagement to a panel of HIV Envs as assessed by Antibody Profiling

  Visit Days 1, 15, 29, 57, 71, 85, 169, 183, and 337

• Characterize rate of B-cell specificity by quantifying antigen-specific responses as assessed through B-cell ELISPOT

  Visit Days 1, 8, 15, 29, 71, 169, 176, 183, and 337

• Characterize magnitude of cell-mediated immune responses elicited across vaccination regimens (including antigen -specific CD4 and CD8 T cell responses) assessed by CD4 and CD8 cellular response assays and after stimulation with HIV-specific antigens.

  Visit Days 1, 4, 8, 29, 71, 169, 170, 176, 183, and 337

Study Arms (4)

Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 1a]

EXPERIMENTAL

Arm 1a \[Co-administration\]: Dose consistent injections (5x10\^10 vp/0.5 mL) of Ad26.Mos4.HIV in a 0.5 mL injection volume and dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1 and 57, followed by a dose-consistent injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 169 (11 participants) OR a 0.5 mL injection and a 1.1 mL injection of Placebo on Study Days 1 and 57, followed by a 1.1 mL injection of Placebo on Study Day 169 (3 participants)

Biological: Ad26.Mos4.HIV in CH505 TF chTrimer + ALFQ [Arm 1a]; Biological: CH505 TF chTrimer + ALFQ [Arm 1a]; Biological: Placebo [Arm 1a]

CH505 TF chTrimer + ALFQ [Arm 1b]

EXPERIMENTAL

Arm 1b \[Trimer Bolus Administration\]: Dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1, 57, and 169 (20 participants) OR a 1.1 mL injection of Placebo on Study Days 1, 57, and 169 (5 participants)

Biological: CH505 TF chTrimer + ALFQ [Arm 1b]; Biological: Placebo [Arm 1b]

Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 2a]

EXPERIMENTAL

Arm 2a \[Rapidvax\]: A lower dose of Ad26.Mos4.HIV (2.5x10\^10 vp/0.25mL) in a 0.25mL injection volume (InjV) + lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50µg MPLA/25µg QS-21) in a 0.5mL InjV \[Study Day (SD) 1\]; followed by rapid, dose escalating injections of CH505 TF chTrimer (100µg, 150µg, and 300µg)+ALFQ (50µg MPLA/25µg QS-21) on SD's 4, 8 (0.5mL InjV), and 15 (0.9mL InjV); followed by injections of Ad26.Mos4.HIV (5x10\^10 vp/0.5mL) in a 0.5mL InjV + CH505 TF chTrimer (300µg)+ALFQ (200µg MPLA/100µg QS 21) in a 1.1mL InjV on SD 57; followed by an injection of CH505 TF chTrimer (300µg)+ALFQ (200µg MPLA/100µg QS 21) in a 1.1mL InjV on SD 169 (11 participants) OR a 0.25mL injection and a 0.5mL injection of Placebo \[P\] on SD 1; followed by 0.5mL, 0.5mL, and 0.9 mL injections of \[P\] on SD's 4, 8, and 15, respectively; followed by a 0.5mL injection + 1.1mL injection of \[P\] on SD 57; followed by a 1.1mL injection of \[P\] on SD 169 (3 participants)

Biological: Ad26.Mos4.HIV in CH505 TF chTrimer +ALFQ [Arm 2a]; Biological: CH505 TF chTrimer +ALFQ [Arm 2a]; Biological: Placebo [Arm 2a]

CH505 TF chTrimer + ALFQ [Arm 2b]

EXPERIMENTAL

Arm 2b \[Trimer Rapidvax\]: A lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS 21) in a 0.5 mL injection volume on Study Day 1; followed by rapid, dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/ 25 µg QS-21) on Study Days 4 (0.5 mL injection volume), 8 (0.5 mL injection volume), and 15 (0.9 mL injection volume); followed by injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Days 57 and 169 (20 participants); OR a 0.5 mL injection of Placebo on Study Days 1, 4, and 8; followed by a 0.9 mL injection of Placebo on Study Day 15; followed by a 1.1 mL injection of Placebo on Study Days 57 and 169 (5 participants)

Biological: CH505 TF chTrimer + ALFQ [Arm 2b]; Biological: Placebo [Arm 2b]

Interventions

Ad26.Mos4.HIV in CH505 TF chTrimer + ALFQ [Arm 1a] BIOLOGICAL

Participants in Arm 1a will receive dose consistent injections (5x10\^10 vp/0.5 mL) of Ad26.Mos4.HIV in a 0.5 mL injection volume and dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1 and 57

Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 1a]

CH505 TF chTrimer + ALFQ [Arm 1a] BIOLOGICAL

Participants in Arm 1a will receive a dose-consistent injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 169.

Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 1a]

Placebo [Arm 1a] BIOLOGICAL

Participants in Arm 1a will receive dose-consistent 0.5 mL injection and a 1.1 mL injection of Placebo on Study Days 1 and 57, followed by a 1.1 mL injection of Placebo on Study Day 169.

Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 1a]

Ad26.Mos4.HIV in CH505 TF chTrimer +ALFQ [Arm 2a] BIOLOGICAL

Participants in Arm 2a will receive a lower dose of Ad26.Mos4.HIV (2.5x10\^10 vp/0.25 mL) in a 0.25 mL injection volume and a lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS-21) in a 0.5 mL injection volume on Study Day 1. Participants in Arm 2a will receive an injection Ad26.Mos4.HIV (5x10\^10 vp/0.5 mL) in a 0.5 mL injection volume and CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 57.

Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 2a]

CH505 TF chTrimer +ALFQ [Arm 2a] BIOLOGICAL

Participants in Arm 2a will receive a rapid, dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/ 25 µg QS-21) on Study Days 4 (0.5 mL injection volume), 8 (0.5 mL injection volume), and 15 (0.9 mL injection volume). Participants in Arm 2a will receive a injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 169.

Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 2a]

Placebo [Arm 2a] BIOLOGICAL

Participants in Arm 2a will receive a 0.25 mL injection and a 0.5 mL injection of Placebo on Study Day 1; followed by 0.5 mL, 0.5 mL, and 0.9 mL injections of Placebo on Study Days 4, 8, and 15, respectively; followed by a 0.5 mL injection and a 1.1 mL injection of Placebo on Study Day 57; followed by a 1.1 mL injection of Placebo on Study Day 169.

Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 2a]

CH505 TF chTrimer + ALFQ [Arm 1b] BIOLOGICAL

Participants in Arm 1b will receive dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1, 57, and 169.

CH505 TF chTrimer + ALFQ [Arm 1b]

Placebo [Arm 1b] BIOLOGICAL

Participants in Arm 1b will receive a 1.1 mL injection of Placebo on Study Days 1, 57, and 169.

CH505 TF chTrimer + ALFQ [Arm 1b]

CH505 TF chTrimer + ALFQ [Arm 2b] BIOLOGICAL

Participants in Arm 2b will receive a lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS 21) in a 0.5 mL injection volume on Study Day 1. Participants in Arm 2b will receive a rapid, dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/ 25 µg QS-21) on Study Days 4 (0.5 mL injection volume), 8 (0.5 mL injection volume), and 15 (0.9 mL injection volume). Participants in Arm 2b will receive a injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Days 57 and 169.

CH505 TF chTrimer + ALFQ [Arm 2b]

Placebo [Arm 2b] BIOLOGICAL

Participants in Arm 2b will receive a 0.5 mL injection of Placebo on Study Days 1, 4, and 8; followed by a 0.9 mL injection of Placebo on Study Day 15; followed by a 1.1 mL injection of Placebo on Study Days 57 and 169.

CH505 TF chTrimer + ALFQ [Arm 2b]

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for participation:
• Male or female, aged 18 to 50 years, inclusive, at the time of enrollment
• Willing and able to read, sign, and date the informed consent form
• Demonstrates an understanding of the study with a passing score (90% or greater) on the TOU by the third attempt, before study-related procedures are performed
• Willing and able to comply with study requirements and be available to attend visits for the duration of study participation
• Must have the means to be contacted by telephone for the duration of study participation
• Willing to have photo or fingerprint taken for identification purposes
• At low risk for HIV acquisition per investigator assessment
• Agrees to refrain from donating blood or plasma outside of this study for at least the duration of study participation
• Healthy based on the physician investigator's clinical judgment after review of past medical history, medication use, vital signs, and an abbreviated physical examination

You may not qualify if:

• first diagnosed within the 12 weeks prior to screening; or
• worsening in terms of clinical outcome in the 24 weeks prior to screening; or
• involves the need for medication that may pose a risk to the participant's safety or impede assessment of adverse events or immunogenicity if they participate in the study.
• Note: Vital signs must be normal by Adverse Event Grading Scales, local normal ranges, or determined to be a normal variant by the physician investigator.
• Note: An abbreviated physical exam differs from a complete exam in that it does not include a genitourinary and rectal exam.
• Laboratory criteria within 45 days prior to enrollment:
• Hemoglobin ≥11.0 g/dL for females; ≥12.5 g/dL for males
• White blood cells (WBC) range: 3,500-9,000 cells/mm\^3
• Platelets between 150,000 - 450,000 cells/µL
• Normal liver function: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤1.25x upper limit of normal
• Serum creatinine ≤1.25x upper limit of normal
• Urinalysis: blood and protein less than 1+ and negative glucose
• Negative HIV serology Note: HIV serology testing will be done via enzyme immunoassay with confirmatory testing of reactive results through a repeat enzyme immunoassay followed by an antibody differentiation immunoassay. After the repeat enzyme immunoassay, if an antibody differentiation immunoassay cannot be done for any reason, then confirmatory testing will be done via Western Blot. HIV rapid testing will not be performed in this study.
• Negative hepatitis B surface antigen (HbsAg)
• Negative hepatitis C serology or negative hepatitis C RNA (viral load) if antibodies are detected Note: Each laboratory screening test that is out of acceptable range can be repeated one time during the screening window if there is a possible alternative explanation for the out of range value or if the out of range value is due to a temporary condition that resolves within the screening visit window. A second screening visit may be conducted outside of the initial screening visit window for volunteers who meet certain criteria if study enrollment and/or participant replacement is ongoing.

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Janssen Vaccines & Prevention B.V.: collaborator
• Henry M. Jackson Foundation for the Advancement of Military Medicine: collaborator
• Duke University: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Makerere University Walter Reed Project: collaborator

Study Sites (1)

Makerere University Walter Reed Project (MUWRP)

Kampala, Uganda

RECRUITING

Related Publications (6)

• Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, Hu D, Tappero JW, Choopanya K; Bangkok Vaccine Evaluation Group. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006 Dec 15;194(12):1661-71. doi: 10.1086/508748. Epub 2006 Nov 3.

  PMID: 17109337 BACKGROUND

• Pauthner M, Havenar-Daughton C, Sok D, Nkolola JP, Bastidas R, Boopathy AV, Carnathan DG, Chandrashekar A, Cirelli KM, Cottrell CA, Eroshkin AM, Guenaga J, Kaushik K, Kulp DW, Liu J, McCoy LE, Oom AL, Ozorowski G, Post KW, Sharma SK, Steichen JM, de Taeye SW, Tokatlian T, Torrents de la Pena A, Butera ST, LaBranche CC, Montefiori DC, Silvestri G, Wilson IA, Irvine DJ, Sanders RW, Schief WR, Ward AB, Wyatt RT, Barouch DH, Crotty S, Burton DR. Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches. Immunity. 2017 Jun 20;46(6):1073-1088.e6. doi: 10.1016/j.immuni.2017.05.007.

  PMID: 28636956 BACKGROUND

• Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, Fire AZ, Roskin KM, Schramm CA, Zhang Z, Zhu J, Shapiro L; NISC Comparative Sequencing Program; Mullikin JC, Gnanakaran S, Hraber P, Wiehe K, Kelsoe G, Yang G, Xia SM, Montefiori DC, Parks R, Lloyd KE, Scearce RM, Soderberg KA, Cohen M, Kamanga G, Louder MK, Tran LM, Chen Y, Cai F, Chen S, Moquin S, Du X, Joyce MG, Srivatsan S, Zhang B, Zheng A, Shaw GM, Hahn BH, Kepler TB, Korber BT, Kwong PD, Mascola JR, Haynes BF. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013 Apr 25;496(7446):469-76. doi: 10.1038/nature12053. Epub 2013 Apr 3.

  PMID: 23552890 BACKGROUND

• Havenar-Daughton C, Carnathan DG, Torrents de la Pena A, Pauthner M, Briney B, Reiss SM, Wood JS, Kaushik K, van Gils MJ, Rosales SL, van der Woude P, Locci M, Le KM, de Taeye SW, Sok D, Mohammed AUR, Huang J, Gumber S, Garcia A, Kasturi SP, Pulendran B, Moore JP, Ahmed R, Seumois G, Burton DR, Sanders RW, Silvestri G, Crotty S. Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer. Cell Rep. 2016 Nov 22;17(9):2195-2209. doi: 10.1016/j.celrep.2016.10.085.

  PMID: 27880897 BACKGROUND

• Genito CJ, Beck Z, Phares TW, Kalle F, Limbach KJ, Stefaniak ME, Patterson NB, Bergmann-Leitner ES, Waters NC, Matyas GR, Alving CR, Dutta S. Liposomes containing monophosphoryl lipid A and QS-21 serve as an effective adjuvant for soluble circumsporozoite protein malaria vaccine FMP013. Vaccine. 2017 Jul 5;35(31):3865-3874. doi: 10.1016/j.vaccine.2017.05.070. Epub 2017 Jun 7.

  PMID: 28596090 BACKGROUND

• Cirelli KM, Carnathan DG, Nogal B, Martin JT, Rodriguez OL, Upadhyay AA, Enemuo CA, Gebru EH, Choe Y, Viviano F, Nakao C, Pauthner MG, Reiss S, Cottrell CA, Smith ML, Bastidas R, Gibson W, Wolabaugh AN, Melo MB, Cossette B, Kumar V, Patel NB, Tokatlian T, Menis S, Kulp DW, Burton DR, Murrell B, Schief WR, Bosinger SE, Ward AB, Watson CT, Silvestri G, Irvine DJ, Crotty S. Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance. Cell. 2019 May 16;177(5):1153-1171.e28. doi: 10.1016/j.cell.2019.04.012. Epub 2019 May 9.

  PMID: 31080066 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Grace Mirembe, MBChB, MMed

  Makerere University Walter Reed Project P.O. Box 16524, Kampala, Uganda

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Grace Mirembe, MBChB, MMed

CONTACT

+256 312 330400; gmirembe@muwrp.org

Hannah Kibuuka, MBChB, MMed, MPH

CONTACT

+256 312 330400; hkibuuka@muwrp.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2023
• First Posted: January 12, 2024
• Study Start: January 30, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)