HIV InfectionsPhase 1NCT04915768
Evaluating the Safety and Immunogenicity of Stabilized CH505 TF chTrimer in Healthy, HIV-uninfected Adult Participants.
A Phase 1 study testing CH505 TF chTrimer, 3M-05-AF and Aluminum hydroxide suspension in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial summary
This is an open-label Phase 1 study to examine the safety and immunogenicity of the CH505 TF chTrimer vaccine with 3M-052-AF +/- Alum adjuvant in healthy adults. The primary hypothesis is that the CH505 TF chTrimer will expand CH103-like B-cell precursors. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- CH505 TF chTrimer, 3M-05-AF and Aluminum hydroxide suspension
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 3 sitesUnited States
- Study dates
- 23 Jan 2023to 15 Jul 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Able and willing to complete the informed consent process, including an Assessment of Understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly.
- 18-55 years old, inclusive, on day of enrollment.
- Available for clinic follow-up through the last clinic visit, willing to undergo lymph node fine needle aspiration and leukapheresis, and willing to be contacted 12 months after the last vaccine administration.
- Agrees not to enroll in another study of an investigational agent during participation in the trial.
- In good general health according to the clinical judgement of the site investigator.
- Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgement of the site investigator.
Show all 19Show fewer
- Assessed as low risk for HIV acquisition per low risk guidelines (see protocol for more information), agrees to discuss HIV infection risks, agrees to risk reduction counseling, and agrees to avoid behavior associated with high risk of HIV exposure through the final study visit. Low risk may include persons stably taking PrEP (pre- exposure prophylaxis) as prescribed for 6 months or longer.
- Hemoglobin >12.5 mg/dL to 18 mg/dL
- White blood cell (WBC) count > 3,500/mm³
- Platelets ≥125,000 /mm³
- Alanine aminotransferase (ALT) < 2.5 x ULN based on the institutional normal range
- Serum creatinine ≤1.1 x ULN based on the institutional normal range
- Blood pressure in the range of 90 to < 160 mmHg systolic and 50 to < 100 mmHg diastolic.
- Negative results for HIV infection by an FDA-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).
- Negative for anti-Hepatitis C antibodies (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV antibodies are detected.
- Negative for Hepatitis B surface antigen.
- For a volunteer capable of becoming pregnant:
- Volunteers who were assigned female sex at birth and are of reproductive potential must agree to use effective means of birth control from at least 21 days prior to enrollment through 8 weeks after their fifth vaccination timepoint (see Appendix E).
- Has negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment.
Who cannot join
- Volunteer who is breast-feeding or pregnant.
- Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
- Systemic glucocorticoid use equal to or greater than prednisone10 mg/day within 3 months prior to enrollment, congenital or acquired immunodeficiency or other systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator.
- Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
- Receipt of any live attenuated vaccine within 4 weeks prior to enrollment.
- Receipt of any vaccines that are not live attenuated within 14 days prior to enrollment; replication incompetent vaccines such as the Jynneos vaccine for the prevention of monkeypox disease are not considered to be live vaccines.
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- ACAM2000 vaccine for Monkeypox received within 30 days prior to enrollment or receipt of study product, or if ACAM2000 received greater than 30 days prior to enrollment or receipt of study product, vaccination scab still present; or planned administration within 30 days after enrollment or receipt of study product.
- Initiation of antigen-based immunotherapy for allergies within the previous year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires PSRT approval.
- Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life greater than 7 days (or unknown half- life) within the past year, PSRT approval is required for enrollment.
- Serious reactions to vaccines that preclude receipt of study injections as determined by the principal investigator or designee. History of serious reaction (eg. hypersensitivity, anaphylaxis) to any vaccine or any component of the study vaccine, including imidazoquinolone (eg, imiquimod).
- Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
- Idiopathic urticaria within the past year.
- Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
- Seizure disorder; febrile seizures as a child or seizures secondary to alcohol withdrawal more than 5 years ago are not exclusionary.
- Asplenia or functional asplenia.
- Active duty and reserve US military personnel.
- Any other chronic or clinically significant condition that in the clinical judgement of the investigator would jeopardize the safety or rights of the study participant, including, but not limited to: clinically significant forms of drug or alcohol abuse, serious psychiatric disorders, or cancer that, in the clinical judgement of the site investigator, has a potential for recurrence (excluding basal cell carcinoma).
- Asthma is excluded if the participant has ANY of the following:
- Required either oral or parenteral corticosteroids for an exacerbation two or more times within the past year; OR
- Needed emergency care, urgent care, hospitalization, or intubation for an acute asthma exacerbation within the past year (eg, would NOT exclude individuals with asthma who meet all other criteria but sought urgent/emergent care solely for asthma medication refills or co-existing conditions unrelated to asthma); OR
- Uses a short-acting rescue inhaler more than 2 days/week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity); OR
- Uses medium-to-high-dose inhaled corticosteroids (greater than 250 mcg fluticasone or therapeutic equivalent per day), whether in single-therapy or dual-therapy inhalers (ie, with a long-acting beta agonist [LABA]);
- Uses more than one medication for maintenance therapy daily. Inclusion of anyone on a stable dose of more than one medication for maintenance therapy daily for greater than two years requires PSRT approval.
- A participant with a history of an immune-mediated disease, either active or remote. Specific examples are listed in Appendix F (AESI index). Not exclusionary:
- remote history of Bell's palsy (>2 years ago) not associated with other neurologic symptoms,
- mild psoriasis that does not require ongoing systemic treatment
- History of allergy to local anesthetic (Novocaine, Lidocaine).
- Investigator concern for difficulty with venous access based upon clinical history and physical examination. For example, history of IV drug abuse or substantial difficulty with previous blood draws.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Brigham and Women's CRS
Boston, Massachusetts, 02115
The Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia, 30030
Vanderbilt Vaccine (VV) CRS
Nashville, Tennessee, 30030
About this study
Official title: A First-in-human Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Stabilized CH505 TF chTrimer in Healthy, HIV-uninfected Adult Participants.
This is an open-label Phase 1 study to examine the safety and immunogenicity of the CH505 TF chTrimer vaccine with 3M-052-AF +/- Alum adjuvant in healthy adults. The primary hypothesis is that the CH505 TF chTrimer will expand CH103-like B-cell precursors.
HVTN 300 Part A examined the safety and immunogenicity of the CH505TF chTrimer with 5 mcg 3M-052-AF + 500 mcg Alum.
Read more
HVTN 300 Part B was added to this protocol with a goal of assessing the optimal dosing and combination of 3M-052-AF and Alum adjuvant, that can potentially lead to improved neutralizing antibody activity and decreased reactogenicity, compared to Part A. Three groups were added to Part B (Group 2: 3 mcg 3M-052-AF without Alum, Group 3: 3 mcg 3M-052 with Alum, and Group 4: 5 mcg 3M-052-AF without Alum).
HVTN 300 Part B is being added to this protocol with a goal of assessing the optimal dosing and combination of 3M-052-AF and Alum adjuvant, that can potentially lead to improved neutralizing antibody activity and decreased reactogenicity, compared to Part A. Three groups have been added to Part B (Group 2: 3 mcg 3M-052-AF without Alum, Group 3: 3 mcg 3M-052 with Alum, and Group 4: 5 mcg 3M-052-AF without Alum).
Read the detailed description
The primary hypothesis is that the CH505 TF chTrimer vaccine will expand B cell precursor lineages capable of ultimately producing autologous and heterologous Tier 2 broadly neutralizing antibodies (bnAbs). Participants receive CH505 TF chTrimer plus 3M-052-AF (at either a 3 mcg dose or a 5 mcg dose), with or without Alum, via two intramuscular injections administered five times throughout the study. Participants are evaluated for safety and immune responses through blood collection at specified timepoints throughout the study. Each participant has up to 18 months of scheduled clinic visits and a follow-up safety assessment 12 months after their final vaccination.
- Conditions
- HIV Infections
- Being tested
- CH505 TF chTrimer, 3M-05-AF, Aluminum hydroxide suspension
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CH505 TF chTrimerBiological
Combined with adjuvants 3M-052-AF and Alum. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle.
3M-05-AFBiological
Combined with CH505 TF chTrimer and Alum adjuvant. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle.
Aluminum hydroxide suspensionBiological
Combined with CH505 TF chTrimer and 3M-052-AF adjuvant. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle
3M-05-AFBiological
Combined with CH505 TF chTrimer. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle.
CH505 TF chTrimerBiological
Combined with adjuvant 3M-052-AF. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Treatment | Experimental | CH505 TF chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF + (500 mcg) Aluminum Hydroxide suspension, administered at months 0, 2, 4, 8 and 12. Receives: Biological: CH505 TF chTrimer; Biological: 3M-05-AF; Biological: Aluminum hydroxide suspension |
| Group 2: Treatment | Experimental | CH505 TF chTrimer 300 mcg admixed with (3 mcg) 3M-052-AF administered at months 0, 2, 4, 8 and 12. Receives: Biological: 3M-05-AF; Biological: CH505 TF chTrimer |
| Group 3: Treatment | Experimental | CH505 cTrimer, 300 mcg admixed with (3 mcg) 3M-052-AF + (500 mcg) Aluminum Hydroxide suspension (Alum) administered at months 0, 2, 4, 8 and 12.*
*On October 13, 2023, errors were identified in the study injection preparation for this Group. The instructions below state that the doses for injections in Group 3 should be 300 mcg of the study vaccine + 3 mcg of 3M-052-AF adjuvant + 500 mcg of Alum adjuvant. However, the step-by-step instructions below for preparing the injection result in 2.2 mcg of 3M-052-AF (instead of 3 mcg) and 556 mcg of Alum (instead of 500 mcg). Thus, Group 3 participants got less 3M-052-AF than intended and more Alum than intended. Receives: Biological: CH505 TF chTrimer; Biological: 3M-05-AF; Biological: Aluminum hydroxide suspension |
| Group 4: Treatment | Experimental | CH505 chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF administered at months 0, 2, 4, 8 and 12. Receives: Biological: 3M-05-AF; Biological: CH505 TF chTrimer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting Local Reactogenicity Events Signs and Symptoms: Erythema and/or Induration
The number and percentage of subjects experiencing each type of reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Measured: Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)
Number of Participants Reporting Local Reactogenicity Events Signs and Symptoms: Pain and/or Tenderness
The number and percentage of subjects experiencing each type of reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Measured: Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)
Number of Participants Showing Systemic Vaccination Reactogenicity Signs and Symptoms
The number and percentage of subjects experiencing each type of systemic reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Measured: Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)
Number of Participants Reporting Unsolicited Adverse Events (AEs) Tabulated by Maximum Severity Grade
The number and percentage of subjects reporting adverse events was tabulated by severity. For a given participant with multiple adverse events reported, maximum severity was taken. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply). All unsolicited adverse events were collected for 30 days after any receipt of study vaccination. Serious adverse events (SAEs), medically attended adverse events (MAAEs), adverse events of special interest (AESIs) and AEs leading to early participant withdrawal or permanent discontinuation which were collected throughout the study and for twelve months following any receipt of study product
Measured: All unsolicited adverse events were collected for 30 days after any receipt of study vaccination. Some adverse events (noted in description) were collected for 12 months following any receipt of study product (up to 104 weeks)
Number of Participants Reporting Serious Adverse Events (SAEs)
The number and percentage of subjects reporting servious adverse events (SAEs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Measured: Serious adverse events (SAEs) were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)
Number of Participants Reporting One or More Medically Attended Adverse Events (MAAEs)
The number and percentage of subjects reporting medically attended adverse events (MAAEs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Measured: Medically attended adverse events (MAAEs) were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)
Number of Participants Reporting Adverse Events of Special Interest (AESIs)
The number and percentage of subjects reporting adverse events of special interest (AESIs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Measured: Adverse events of special interest (AESIs)were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)
Number of Participants With Study Product Discontinuation Associated With an Unsolicited AE or Reactogenicity
From the vaccination and adverse event case report forms, counts are tabulated by treatment arm
Measured: Measured through 12 months following any receipt of study product (up to 104 weeks
Frequency of the CD4 Binding-site, V2 Apex and V3 Glycan (bnAb Region at the Base of the V3 Loop), and/or CH505TF-specific IgG+ B Cells
Measured by flow cytometry analysis
Measured: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Response Rate of Serum Antibody Neutralization of Vaccine-matched Tier 2 HIV-1 Strains
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. Response to an isolate was considered positive if the neutralization titer was above a pre-specified cutoff. The pre-specified positivity call was an ID50 (or ID80) value ≥ 10,
Measured: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Magnitude of Serum Antibody Neutralization of Vaccine-matched Tier 2 HIV-1 Strains
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells.
Measured: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Secondary outcomes (4)
Response Rate of Serum IgG Binding Antibodies
Assessed by binding Ab multiplex assay (BAMA)
Measured: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Magnitude of Serum IgG Binding Antibodies
Assessed by binding Ab multiplex assay (BAMA)
Measured: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Response Rate of Serum Antibody Neutralization of Heterologous HIV-1 Strains
"Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. Criterion to qualify for the global panel: Any samples resulting in >60 ID50 titer against CH505TF were tested against the global panel of heterologous Env-pseudotyped viruses that exhibited a tier 2 neutralization phenotype. Response to an isolate was considered positive if the neutralization titer was above a pre-specified cutoff. The pre-specified positivity call was an ID50 (or ID80) value ≥ 10,"
Measured: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Magnitude of Serum Antibody Neutralization of Heterologous HIV-1 Strains
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. Criterion to qualify for the global panel: Any samples resulting in >60 ID50 titer against CH505TF were tested against the global panel of heterologous Env-pseudotyped viruses that exhibited a tier 2 neutralization phenotype.
Measured: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2021
- Study start23 Jan 2023
- Primary completion15 Jul 2025
- Study completion15 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kenneth H Mayer, M.D., Study chair, Beth Israel Deaconess Medical CenterLindsey R Baden, M.D., Study chair, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04915768
- Sponsor's protocol ID
- HVTN 300
- Other IDs
- 38705
- Status last verified
- Mar 2026
- First submitted
- 1 Jun 2021
- Last updated
- 14 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Walsh SR, Hahn WO, Williams WB, Hyrien O, Yu PC, Parks KR, Edwards RJ, Parks R, Barr M, Polakowski LL, Tindale I, Jones M, Yurdadon C, Burnham R, Yeh CH, Heptinstall J, Seaton KE, Andriesen JG, Sagawa Z, Miner MD, De Rosa S, McElrath MJ, Corey L, Tomaras GD, Montefiori DC, Haynes BF, Mayer KH, Baden LR; NIAID HVTN 300 Study Group. Safety and immunogenicity of an HIV envelope trimer immunogen that elicits CD4 binding site neutralizing antibody precursors (HVTN 300). medRxiv [Preprint]. 2026 Apr 3:2026.03.31.26349761. doi: 10.64898/2026.03.31.26349761.
PubMed 41959788
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-in-human Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Stabilized CH505 TF chTrimer in Healthy, HIV-uninfected Adult Participants.
- ClinicalTrials.gov ID
- NCT04915768
- Acronym / sponsor ID
- HVTN 300
- Conditions
- HIV Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 23 Jan 2023 (actual)
- Primary completion
- 15 Jul 2025 (actual)
- Study completion
- 15 Jul 2025 (actual)
- First posted
- 7 Jun 2021 (actual)
- Results
- Posted 27 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label Phase 1 study to examine the safety and immunogenicity of the CH505 TF chTrimer vaccine with 3M-052-AF +/- Alum adjuvant in healthy adults. The primary hypothesis is that the CH505 TF chTrimer will expand CH103-like B-cell precursors.
HVTN 300 Part A examined the safety and immunogenicity of the CH505TF chTrimer with 5 mcg 3M-052-AF + 500 mcg Alum.
HVTN 300 Part B was added to this protocol with a goal of assessing the optimal dosing and combination of 3M-052-AF and Alum adjuvant, that can potentially lead to improved neutralizing antibody activity and decreased reactogenicity, compared to Part A. Three groups were added to Part B (Group 2: 3 mcg 3M-052-AF without Alum, Group 3: 3 mcg 3M-052 with Alum, and Group 4: 5 mcg 3M-052-AF without Alum).
HVTN 300 Part B is being added to this protocol with a goal of assessing the optimal dosing and combination of 3M-052-AF and Alum adjuvant, that can potentially lead to improved neutralizing antibody activity and decreased reactogenicity, compared to Part A. Three groups have been added to Part B (Group 2: 3 mcg 3M-052-AF without Alum, Group 3: 3 mcg 3M-052 with Alum, and Group 4: 5 mcg 3M-052-AF without Alum).
Detailed description
The primary hypothesis is that the CH505 TF chTrimer vaccine will expand B cell precursor lineages capable of ultimately producing autologous and heterologous Tier 2 broadly neutralizing antibodies (bnAbs). Participants receive CH505 TF chTrimer plus 3M-052-AF (at either a 3 mcg dose or a 5 mcg dose), with or without Alum, via two intramuscular injections administered five times throughout the study. Participants are evaluated for safety and immune responses through blood collection at specified timepoints throughout the study. Each participant has up to 18 months of scheduled clinic visits and a follow-up safety assessment 12 months after their final vaccination.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1: Treatment | Experimental | Biological: CH505 TF chTrimer, Biological: 3M-05-AF, Biological: Aluminum hydroxide suspensionCH505 TF chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF + (500 mcg) Aluminum Hydroxide suspension, administered at months 0, 2, 4, 8 and 12. |
| Group 2: Treatment | Experimental | Biological: 3M-05-AF, Biological: CH505 TF chTrimerCH505 TF chTrimer 300 mcg admixed with (3 mcg) 3M-052-AF administered at months 0, 2, 4, 8 and 12. |
| Group 3: Treatment | Experimental | Biological: CH505 TF chTrimer, Biological: 3M-05-AF, Biological: Aluminum hydroxide suspensionCH505 cTrimer, 300 mcg admixed with (3 mcg) 3M-052-AF + (500 mcg) Aluminum Hydroxide suspension (Alum) administered at months 0, 2, 4, 8 and 12.* *On October 13, 2023, errors were identified in the study injection preparation for this Group. The instructions below state that the doses for injections in Group 3 should be 300 mcg of the study vaccine + 3 mcg of 3M-052-AF adjuvant + 500 mcg of Alum adjuvant. However, the step-by-step instructions below for preparing the injection result in 2.2 mcg of 3M-052-AF (instead of 3 mcg) and 556 mcg of Alum (instead of 500 mcg). Thus, Group 3 participants got less 3M-052-AF than intended and more Alum than intended. |
| Group 4: Treatment | Experimental | Biological: 3M-05-AF, Biological: CH505 TF chTrimerCH505 chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF administered at months 0, 2, 4, 8 and 12. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Able and willing to complete the informed consent process, including an Assessment of Understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly.
- 18-55 years old, inclusive, on day of enrollment.
- Available for clinic follow-up through the last clinic visit, willing to undergo lymph node fine needle aspiration and leukapheresis, and willing to be contacted 12 months after the last vaccine administration.
- Agrees not to enroll in another study of an investigational agent during participation in the trial.
- In good general health according to the clinical judgement of the site investigator.
Key exclusion criteria (28 listed)
- Volunteer who is breast-feeding or pregnant.
- Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
- Systemic glucocorticoid use equal to or greater than prednisone10 mg/day within 3 months prior to enrollment, congenital or acquired immunodeficiency or other systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator.
- Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
- Receipt of any live attenuated vaccine within 4 weeks prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CH505 TF chTrimerCombined with adjuvants 3M-052-AF and Alum. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle. | Biological | Group 1: Treatment, Group 3: Treatment |
| 3M-05-AFCombined with CH505 TF chTrimer and Alum adjuvant. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle. | Biological | Group 1: Treatment, Group 3: Treatment |
| Aluminum hydroxide suspensionCombined with CH505 TF chTrimer and 3M-052-AF adjuvant. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle | Biological | Group 1: Treatment, Group 3: Treatment |
| 3M-05-AFCombined with CH505 TF chTrimer. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle. | Biological | Group 2: Treatment, Group 4: Treatment |
| CH505 TF chTrimerCombined with adjuvant 3M-052-AF. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle. | Biological | Group 2: Treatment, Group 4: Treatment |
Primary outcome
Number of Participants Reporting Local Reactogenicity Events Signs and Symptoms: Erythema and/or Induration
Time frame: Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)
The number and percentage of subjects experiencing each type of reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Number of Participants Reporting Local Reactogenicity Events Signs and Symptoms: Pain and/or Tenderness
Time frame: Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)
The number and percentage of subjects experiencing each type of reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Number of Participants Showing Systemic Vaccination Reactogenicity Signs and Symptoms
Time frame: Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)
The number and percentage of subjects experiencing each type of systemic reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Number of Participants Reporting Unsolicited Adverse Events (AEs) Tabulated by Maximum Severity Grade
Time frame: All unsolicited adverse events were collected for 30 days after any receipt of study vaccination. Some adverse events (noted in description) were collected for 12 months following any receipt of study product (up to 104 weeks)
The number and percentage of subjects reporting adverse events was tabulated by severity. For a given participant with multiple adverse events reported, maximum severity was taken. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply). All unsolicited adverse events were collected for 30 days after any receipt of study vaccination. Serious adverse events (SAEs), medically attended adverse events (MAAEs), adverse events of special interest (AESIs) and AEs leading to early participant withdrawal or permanent discontinuation which were collected throughout the study and for twelve months following any receipt of study product
Number of Participants Reporting Serious Adverse Events (SAEs)
Time frame: Serious adverse events (SAEs) were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)
The number and percentage of subjects reporting servious adverse events (SAEs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Number of Participants Reporting One or More Medically Attended Adverse Events (MAAEs)
Time frame: Medically attended adverse events (MAAEs) were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)
The number and percentage of subjects reporting medically attended adverse events (MAAEs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Number of Participants Reporting Adverse Events of Special Interest (AESIs)
Time frame: Adverse events of special interest (AESIs)were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)
The number and percentage of subjects reporting adverse events of special interest (AESIs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]
Number of Participants With Study Product Discontinuation Associated With an Unsolicited AE or Reactogenicity
Time frame: Measured through 12 months following any receipt of study product (up to 104 weeks
From the vaccination and adverse event case report forms, counts are tabulated by treatment arm
Frequency of the CD4 Binding-site, V2 Apex and V3 Glycan (bnAb Region at the Base of the V3 Loop), and/or CH505TF-specific IgG+ B Cells
Time frame: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Measured by flow cytometry analysis
Response Rate of Serum Antibody Neutralization of Vaccine-matched Tier 2 HIV-1 Strains
Time frame: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. Response to an isolate was considered positive if the neutralization titer was above a pre-specified cutoff. The pre-specified positivity call was an ID50 (or ID80) value ≥ 10,
Magnitude of Serum Antibody Neutralization of Vaccine-matched Tier 2 HIV-1 Strains
Time frame: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells.
4 secondary outcomes
Response Rate of Serum IgG Binding Antibodies
Time frame: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Magnitude of Serum IgG Binding Antibodies
Time frame: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Response Rate of Serum Antibody Neutralization of Heterologous HIV-1 Strains
Time frame: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Magnitude of Serum Antibody Neutralization of Heterologous HIV-1 Strains
Time frame: Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41959788Walsh SR, Hahn WO, Williams WB, Hyrien O, Yu PC, Parks KR, Edwards RJ, Parks R, Barr M, Polakowski LL, Tindale I, Jones M, Yurdadon C, Burnham R, Yeh CH, Heptinstall J, Seaton KE, Andriesen JG, Sagawa Z, Miner MD, De Rosa S, McElrath MJ, Corey L, Tomaras GD, Montefiori DC, Haynes BF, Mayer KH, Baden LR; NIAID HVTN 300 Study Group. Safety and immunogenicity of an HIV envelope trimer immunogen that elicits CD4 binding site neutralizing antibody precursors (HVTN 300). medRxiv [Preprint]. 2026 Apr 3:2026.03.31.26349761. doi: 10.64898/2026.03.31.26349761.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth H Mayer, M.D. study chair
Beth Israel Deaconess Medical Center
Lindsey R Baden, M.D. study chair
Brigham and Women's Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CH505 TF chTrimer, 3M-05-AF and Aluminum hydroxide suspension in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Reporting Local Reactogenicity Events Signs and Symptoms: Erythema and/or Induration (time frame: Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04915768, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2026; AzTrials last refreshed its copy on 26 Oct 2026.