CompletedNCT03409276Updated Apr 25, 2022Results posted

Evaluating the Safety and Immunogenicity of Env (A,B,C,A/E)/Gag (C) DNA and gp120 (A,B,C,A/E) Protein/GLA-SE HIV Vaccines, Given Individually or Co-administered, in Healthy, HIV-1-Uninfected Adults

A Phase 1 interventional study of env (A,B,C,A/E)/gag (C) DNA Vaccine and gp120 (A,B,C,A/E) Protein Vaccine in HIV Infections, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 6 sites in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-04-25.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Prevention

Phase: Phase 1
Study type: Interventional
Enrollment: 60
Allocation: Randomized
Ages: 18 Years to 50 Years
Sex: All

Study summary

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein/GLA-SE HIV-1 vaccines (PDPHV-201401) as a prime-boost regimen or co-administered in repeated doses, in healthy, HIV-1-uninfected adults.

Read the detailed description

This study will evaluate the safety, tolerability, and immunogenicity of env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein/GLA-SE HIV-1 vaccines (PDPHV-201401) as a prime-boost regimen or co-administered in repeated doses, in healthy, HIV-1-uninfected adults.

The study will be conducted in two parts (Part A and Part B).

Participants in Part A will be randomly assigned to either Group 1 (Treatment) or Group 1 (Control). Participants in Group 1 (Treatment) will receive the gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant on Day 0 and Month 2. Participants in Group 1 (Control) will receive placebo on Day 0 and Month 2.

Researchers will evaluate study data from Part A before enrolling participants in Part B.

Participants in Part B will be enrolled in either Groups 2 or 3. Within Group 2, participants will be randomly assigned to either Group 2 (Treatment) or Group 2 (Control). Participants in Group 2 (Treatment) will receive the env (A,B,C,A/E)/gag (C) DNA vaccine and placebo on Day 0 and Months 1 and 3. At Months 6 and 8, participants will receive the gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant and a placebo vaccine. Participants in Group 2 (Control) will receive placebo on Day 0 and Months 1, 3, 6, and 8.

Participants in Group 3 will be randomly assigned to either Group 3 (Treatment) or Group 3 (Control). Participants in Group 3 (Treatment) will receive the env (A,B,C,A/E)/gag (C) DNA vaccine and the gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant on Day 0 and Months 1, 3, 6, and 8. Participants in Group 3 (Control) will receive placebo on Day 0 and Months 1, 3, 6, and 8.

Study visits for participants in Part A will occur on Day 0, Week 2, and Months 2, 2.5, 5, and 8. Study visits for participants in Part B will occur on Day 0, Week 2, and Months 1, 1.5, 3, 3.5, 6, 6.5, 8, 8 + 1 Week, 8.5, 11, and 14. Visits may include physical examinations, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires. Participants in Part B may also have optional saliva, semen, cervical fluid, rectal fluid, and stool sample collection.

Study staff will contact all participants 12 months after the last vaccination for follow-up health monitoring.

Conditions studied

HIV Infections

Browse trials for

HIV Infections 4,256

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

General and Demographic Criteria

Age of 18 to 50 years
Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
Ability and willingness to provide informed consent
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
Willing to be contacted 12 months after the last vaccination
Agrees not to enroll in another study of an investigational research agent
Good general health as shown by medical history, physical exam, and screening laboratory tests

HIV-Related Criteria:

Willingness to receive HIV test results
Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit.

Laboratory Inclusion Values

Hemogram/Complete Blood Count (CBC)

Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
White blood cell count equal to 3,300 to 12,000 cells/mm\^3
Total lymphocyte count greater than or equal to 800 cells/mm\^3
Remaining differential either within institutional normal range or with site physician approval
Platelets equal to 125,000/mm\^3 to 450,000/mm\^3

Chemistry

Chemistry panel: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal; creatinine less than or equal to institutional upper limit of normal.

Virology

Negative HIV-1 and -2 blood test: US volunteers must have a negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA).
Negative Hepatitis B surface antigen (HBsAg)
Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive

Urine

Normal urine:
- Negative urine glucose, and
- Negative or trace urine protein, and
- Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range).

Reproductive Status

Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.
Reproductive status: A volunteer who was born female must:
- Agree to consistently use effective contraception (see the protocol for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment until after the last required protocol clinic visit. Effective contraception is defined as using the following methods:
- Condoms (male or female) with or without a spermicide,
- Diaphragm or cervical cap with spermicide,
- Intrauterine device (IUD),
- Hormonal contraception, or
- Any other contraceptive method approved by the HVTN 124 Protocol Safety Review Team (PSRT)
- Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy);
- Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;
- Or be sexually abstinent.
Volunteers who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

Exclusion criteria

Exclusion Criteria:

General

Blood products received within 120 days before first vaccination
Investigational research agents received within 30 days before first vaccination
Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known hyperlipidemia
Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 124 study
Pregnant or breastfeeding
Active duty and reserve US military personnel

Vaccines and other Injections

HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 124 PSRT will determine eligibility on a case-by-case basis.
Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made by the HVTN 124 PSRT for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 124 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 124 PSRT on a case-by-case basis.
Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)
Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination

Immune System

Immunosuppressive medications received within 168 days before first vaccination (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral prednisone or equivalent at doses less than 60 mg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment.)
Serious adverse reactions to vaccines or to vaccine components including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)
Immunoglobulin received within 60 days before first vaccination
Autoimmune disease, connective tissue disease, or history of vasculitis, e.g., leukocytoclastic vasculitis, Henoch-Schonlein purpura
Immunodeficiency

Clinically significant medical conditions

Untreated or incompletely treated syphilis infection
Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
- A process that would affect the immune response,
- A process that would require medication that affects the immune response,
- Any contraindication to repeated injections or blood draws,
- A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,
- A condition or process for which signs or symptoms could be confused with reactions to vaccine, or
- Any condition specifically listed among the exclusion criteria below.
Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent
Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
Current anti-tuberculosis (TB) prophylaxis or therapy
Asthma exclusion criteria: Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a volunteer who:
- Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or
- Uses moderate/high dose inhaled corticosteroids, or
- In the past year has either of the following:
- Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;
- Needed emergency care, urgent care, hospitalization, or intubation for asthma.
Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
Thyroidectomy, or thyroid disease requiring medication during the last 12 months
Hypertension:
- If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg diastolic. For these volunteers, blood pressure must be less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment.
- If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure greater than or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or equal to 100 mm Hg at enrollment.
Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study)
Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
Asplenia: any condition resulting in the absence of a functional spleen
History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.

Study design

Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 60 participants (actual)

Study arms

Experimental
Group 1 (Treatment): Protein Vaccine/GLA-SE
Participants will receive 400 mcg of gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant at Day 0 and Month 2.
Biological: gp120 (A,B,C,A/E) Protein Vaccine · Biological: GLA-SE adjuvant
Placebo comparator
Group 1 (Control)
Participants will receive placebo at Day 0 and Month 2.
Biological: Placebo
Experimental
Group 2 (Treatment) DNA Vaccine+Placebo+Protein Vaccine/GLA-SE
Participants will receive 2 mg of env (A,B,C,A/E)/gag (C) DNA vaccine and placebo at Day 0 and Months 1 and 3. Participants will receive 400 mcg of gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant and a placebo vaccine at Months 6 and 8.
Biological: env (A,B,C,A/E)/gag (C) DNA Vaccine · Biological: gp120 (A,B,C,A/E) Protein Vaccine · Biological: Placebo · Biological: GLA-SE adjuvant
Placebo comparator
Group 2 (Control)
Participants will receive placebo at Day 0 and Months 1, 3, 6, and 8.
Biological: Placebo
Experimental
Group 3 (Treatment): DNA Vaccine+Protein Vaccine/GLA-SE
Participants will receive 2 mg of the env (A,B,C,A/E)/gag (C) DNA vaccine and 400 mcg of gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant at Day 0 and Months 1, 3, 6, and 8.
Biological: env (A,B,C,A/E)/gag (C) DNA Vaccine · Biological: gp120 (A,B,C,A/E) Protein Vaccine · Biological: GLA-SE adjuvant
Placebo comparator
Group 3 (Control)
Participants will receive placebo at Day 0 and Months 1, 3, 6, and 8.
Biological: Placebo

Interventions

Biologicalenv (A,B,C,A/E)/gag (C) DNA Vaccine
Administered by intramuscular injection in the deltoid.
Also known as: Polyvalent DNA (PDPHV-201401) Plasmid
Biologicalgp120 (A,B,C,A/E) Protein Vaccine
Administered by intramuscular injection in the deltoid.
Also known as: PDPHV-201401 Recombinant Proteins gp120A, gp120B, gp120C, gp120AE
BiologicalPlacebo
Sodium Chloride for Injection, USP 0.9%; Administered by intramuscular injection in the deltoid.
BiologicalGLA-SE adjuvant
Administered by intramuscular injection in the deltoid.
Also known as: glucopyranosyl lipid adjuvant-stable emulsion

What researchers measure

Primary outcomes

Number of Participants Reporting Local Reactogenicity Signs and Symptoms
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. The maximum grade observed for each symptom over the time frame is presented.
Time frame: Measured through 3 days after participants' each vaccination at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
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. The maximum grade observed for each symptom over the time frame is presented.
Time frame: Measured through 3 days after participants' each vaccination at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product
For participants reporting multiple AEs over the time frame, the maximum relationship is counted.
Time frame: Measured through 30 days after each vaccine dose at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Number of Participants Reporting Adverse Events (AEs), by Severity Grade
For participants reporting multiple AEs over the time frame, the maximum severity grade is counted.
Time frame: Measured through 30 days after each vaccine dose at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Number of Participants Reporting Serious Adverse Events (SAEs)
Measured as outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual).
Time frame: Measured through Month 8 for part A and Month 14 for part B
Number of Participants Reporting Adverse Events of Special Interest (AESIs)
Adverse events of special interest were described in Appendix N of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases. There were no adverse events of special interest reported by any participant.
Time frame: Measured through Month 8 for part A and Month 14 for part B
Numbers of Participants With Grade 1 or Higher Local Laboratory Results
The number (percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria or above as specified in the DAIDS AE Grading Table were tabulated by treatment arm for each post-vaccination time point. Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.
Time frame: Measured during Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Alk Phos, AST, ALT in UL
Laboratory results are summarized by analyte and timepoint.
Time frame: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Hemoglobin, Creatinine in g/dL
Laboratory results are summarized by analyte and timepoint.
Time frame: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
WBC, Platelets, Lymphocytes, Neutrophils in Thousand Cells/Cubic mm
Laboratory results are summarized by analyte and timepoint.
Time frame: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
From the study product discontinuation form, study product administration reasons are tabulated by treatment arm
Time frame: Measured through study completion, up to 31 months

Secondary outcomes

Occurrence of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination
Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500.
Time frame: Measured at Month 2.5 for part A and 8.5 for part B
Levels of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination
Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 12).
Time frame: Measured at Month 2.5 for part A and 8.5 for part B
Breadth of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination
Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. Magnitude-breadth (MB) curves characterized the magnitude (Binding antibody MFI\* at 1:50 dilution and titer) and breadth (number of antigens with positive response at given MFI\* or titer) of each individual plasma sample assayed against a panel of antigens. The x-axis represents the response magnitude and the y-axis represents the fraction of antigens with response magnitude greater than the x-axis value. In addition to the individual sample specific curves, the group-specific curve displayed the average MB across all participants in that group. The area-under-the-magnitude-breadth curve (AUC-MB) was calculated as the average of the log10 MFI\* (log10 titer) over the panel of antigens.
Time frame: Measured at Month 2.5 for part A and 8.5 for part B
Part B: Occurrence of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination
Neutralizing antibodies against HIV1were measured as a function of reductions in Tat-regulatedluciferase (Luc) reporter gene expression in TZM-blcells. The assay performed in TZM-bl cells measured neutralization titers against a panel of Env-pseudotyped viruses that exhibit the following naturalization phenotypes. Response to a virus/isolate was considered positive if the neutralization titer was above a prespecified cutoff. A titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (ID50 and ID80, cells only). The prespecified cutoff was 20 for MW965.26 (Tier 1a) and 10 for other viruses.
Time frame: Measured at Month 8.5 for part B only
Part B: Levels of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination
Neutralizing antibodies against HIV1were measured as a function of reductions in Tat-regulatedluciferase (Luc) reporter gene expression in TZM-blcells. The assay performed in TZM-bl cells measured neutralization titers against a panel of Env-pseudotyped viruses that exhibit the following naturalization phenotypes. Response to a virus/isolate was considered positive if the neutralization titer was above a prespecified cutoff. A titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (ID50 and ID80, cells only). The prespecified cutoff was 20 for MW965.26 (Tier 1a) and 10 for other viruses.
Time frame: Measured at Month 8.5 for part B only
Breadth of gp70-V1V2 IgG and gp120 IgA, Assessed by Binding Antibody Multiplex Assay, and ADCC Activities Against HIV-1 Subtypes A, B, C and A/E Two Weeks After the Last Vaccination in Part B
For Binding Antibody Multiplex Assay, gp70-V1V2 IgG, the area-under-the-magnitude-breadth curve (AUC-MB) was calculated as the average of the log10 MFI\* (log10 titer) over the panel of antigens. For ADCC GranToxiLux, AUC-MB was calculated as the average of the AUC over the panel of antigens, where AUC is defined as nonparametric area under the net percent granzyme B activity vs log10 (dilution) curve ("AUC"), calculated using the trapezoidal rule, and setting any net percent granzyme B activity below 0% to 0%. For ADCC Luciferase, (AUC-MB) was calculated as the average of the pAUC over the panel of antigens, where pAUC is defined as nonparametric partial area under the baseline subtracted curves ("pAUC"), calculated using the trapezoidal rule on the first four dilutions of the baseline subtracted curves, setting baseline subtracted loss Luciferase activity less than 0% to zero.
Time frame: Measured at Month 8.5 for part B only
Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.
PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value \<=0.00001. Please note the above analyses were applied by the lab to determine the response positivity, not the planned analyses for the study outcome measures. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.
Time frame: Measured at Month 8.5 for part B only
Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.
PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value \<=0.00001. Please note the above analyses were applied by the lab to determine the response positivity, not the planned analyses for the study outcome measures. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.
Time frame: Measured at Month 8.5 for part B only
Occurrence of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.
PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value \<=0.00001. Please note the above analyses were applied by the lab to determine the response positivity, not the planned analyses for the study outcome measures. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.
Time frame: Measured at Month 8.5 for part B only
Level of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.
PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value \<=0.00001. Please note the above analyses were applied by the lab to determine the response positivity, not the planned analyses for the study outcome measures. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.
Time frame: Measured at Month 8.5 for part B only

Results

Posted Apr 25, 2022

Participant flow

Participant flow — Overall Study
Milestone	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Started	2	10	6	21	21
Month 2.5 immunogenicity cohort	2	10	0	0	0
Month 8.5 immunogenicity cohort	0	0	6	19	16
Completed	2	10	6	19	18
Not completed	0	0	0	2	3
Withdrew: Withdrawal by subject	0	0	0	0	1
Withdrew: Lost to follow-up	0	0	0	2	2

Outcome measures

PrimaryNumber of Participants Reporting Local Reactogenicity Signs and Symptoms

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. The maximum grade observed for each symptom over the time frame is presented.

Time frame:: Measured through 3 days after participants' each vaccination at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Reported as:: Count of participants · Participants

Number of Participants Reporting Local Reactogenicity Signs and Symptoms
Participants	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Pain — None	2	5	5	3	1
Pain — Mild	0	4	1	12	15
Pain — Moderate	0	1	0	5	4
Pain — Severe	0	0	0	1	1
Pain — Potentially Life-threatening	0	0	0	0	0
Tenderness — None	2	3	4	1	0
Tenderness — Mild	0	6	2	15	17
Tenderness — Moderate	0	1	0	4	3
Tenderness — Severe	0	0	0	1	1
Tenderness — Potentially Life-threatening	0	0	0	0	0
Pain and/or Tenderness — None	2	3	4	1	0
Pain and/or Tenderness — Mild	0	6	2	13	15
Pain and/or Tenderness — Moderate	0	1	0	6	5
Pain and/or Tenderness — Severe	0	0	0	1	1
Pain and/or Tenderness — Potentially Life-threatening	0	0	0	0	0
Erythema — None	2	10	6	14	13
Erythema — Mild	0	0	0	0	2
Erythema — Moderate	0	0	0	2	4
Erythema — Severe	0	0	0	5	2
Erythema — Potentially Life-threatening	0	0	0	0	0
Induration — None	2	10	6	16	14
Induration — Mild	0	0	0	1	3
Induration — Moderate	0	0	0	0	2
Induration — Severe	0	0	0	4	2
Induration — Potentially Life-threatening	0	0	0	0	0
Erythema and/or Induration — None	2	10	6	14	12
Erythema and/or Induration — Mild	0	0	0	0	3
Erythema and/or Induration — Moderate	0	0	0	2	4
Erythema and/or Induration — Severe	0	0	0	5	2
Erythema and/or Induration — Potentially Life-threatening	0	0	0	0	0

PrimaryNumber of Participants Reporting Systemic Reactogenicity Signs and Symptoms

Time frame:: Measured through 3 days after participants' each vaccination at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Reported as:: Count of participants · Participants

Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Participants	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Malaise and/or fatigue — None	1	5	2	4	6
Malaise and/or fatigue — Mild	1	5	1	8	8
Malaise and/or fatigue — Moderate	0	0	2	7	6
Malaise and/or fatigue — Severe	0	0	1	2	1
Malaise and/or fatigue — Potentially Life-threatening	0	0	0	0	0
Myalgia — None	1	6	4	8	11
Myalgia — Mild	1	4	2	9	7
Myalgia — Moderate	0	0	0	2	1
Myalgia — Severe	0	0	0	2	2
Myalgia — Potentially Life-threatening	0	0	0	0	0
Headache — None	1	5	2	3	9
Headache — Mild	1	5	3	10	8
Headache — Moderate	0	0	1	8	2
Headache — Severe	0	0	0	0	2
Headache — Potentially Life-threatening	0	0	0	0	0
Nausea — None	1	8	4	12	15
Nausea — Mild	1	2	1	6	4
Nausea — Moderate	0	0	1	3	2
Nausea — Severe	0	0	0	0	0
Nausea — Potentially Life-threatening	0	0	0	0	0
Vomiting — None	2	10	6	17	18
Vomiting — Mild	0	0	0	3	1
Vomiting — Moderate	0	0	0	1	2
Vomiting — Severe	0	0	0	0	0
Vomiting — Potentially Life-threatening	0	0	0	0	0
Chills — None	2	10	6	11	15
Chills — Mild	0	0	0	4	4
Chills — Moderate	0	0	0	4	0
Chills — Severe	0	0	0	2	2
Chills — Potentially Life-threatening	0	0	0	0	0
Arthralgia — None	2	8	6	10	17
Arthralgia — Mild	0	1	0	8	2
Arthralgia — Moderate	0	1	0	1	1
Arthralgia — Severe	0	0	0	2	1
Arthralgia — Potentially Life-threatening	0	0	0	0	0
Max. Systemic Symptoms — None	1	3	2	3	5
Max. Systemic Symptoms — Mild	1	6	0	8	8
Max. Systemic Symptoms — Moderate	0	1	3	8	6
Max. Systemic Symptoms — Severe	0	0	1	2	2
Max. Systemic Symptoms — Potentially Life-threatening	0	0	0	0	0
Temperature — None	2	10	6	15	16
Temperature — Mild	0	0	0	2	3
Temperature — Moderate	0	0	0	3	2
Temperature — Severe	0	0	0	0	0
Temperature — Potentially Life-threatening	0	0	0	1	0

PrimaryNumber of Participants Reporting Adverse Events (AEs), by Relationship to Study Product

For participants reporting multiple AEs over the time frame, the maximum relationship is counted.

Time frame:: Measured through 30 days after each vaccine dose at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Reported as:: Count of participants · Participants

Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product
Participants	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Related	0	0	0	5	2
Not Related	2	6	5	14	16
No AE reported	0	4	1	2	3

PrimaryNumber of Participants Reporting Adverse Events (AEs), by Severity Grade

For participants reporting multiple AEs over the time frame, the maximum severity grade is counted.

Time frame:: Measured through 30 days after each vaccine dose at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B
Reported as:: Count of participants · Participants

Number of Participants Reporting Adverse Events (AEs), by Severity Grade
Participants	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Mild	0	2	1	0	2
Moderate	2	4	4	18	14
Severe	0	0	0	1	2
No AE reported	0	4	1	2	3

PrimaryNumber of Participants Reporting Serious Adverse Events (SAEs)

Measured as outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual).

Time frame:: Measured through Month 8 for part A and Month 14 for part B
Reported as:: Count of participants · Participants

Number of Participants Reporting Serious Adverse Events (SAEs)
Participants	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Number of Participants Reporting Serious Adverse Events (SAEs)	0	0	0	0	0

PrimaryNumber of Participants Reporting Adverse Events of Special Interest (AESIs)

Adverse events of special interest were described in Appendix N of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases. There were no adverse events of special interest reported by any participant.

Time frame:: Measured through Month 8 for part A and Month 14 for part B
Reported as:: Count of participants · Participants

Number of Participants Reporting Adverse Events of Special Interest (AESIs)
Participants	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Number of Participants Reporting Adverse Events of Special Interest (AESIs)	0	0	0	0	0

PrimaryNumbers of Participants With Grade 1 or Higher Local Laboratory Results

The number (percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria or above as specified in the DAIDS AE Grading Table were tabulated by treatment arm for each post-vaccination time point. Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

Time frame:: Measured during Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Reported as:: Count of participants · Participants

Numbers of Participants With Grade 1 or Higher Local Laboratory Results
Participants	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
AST (U/L)- Day42	—	—	0	1	0
AST (U/L)- Day98	—	—	0	0	1
AST (U/L)- Day140	0	1	—	—	—
ALT (SGPT) (U/L)- Day42	—	—	0	1	0
Hemoglobin (g/dL)- Day182	—	—	0	2	0
Hemoglobin (g/dL)- Day238	—	—	0	1	0
Hemoglobin (g/dL)- Day334	—	—	0	1	0
Creatinine (g/dL)- Day14	0	2	0	0	0
Creatinine (g/dL)- Day42	—	—	0	0	1
Creatinine (g/dL)- Day98	—	—	0	2	0
Creatinine (g/dL)- Day182	—	—	0	2	2
Creatinine (g/dL)- Day334	—	—	1	0	1

PrimaryAlk Phos, AST, ALT in UL

Laboratory results are summarized by analyte and timepoint.

Time frame:: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Reported as:: Median · U/L

Alk Phos, AST, ALT in UL
U/L	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Alkaline Phosphatase (U/L)- Screening	61 (58 to 64)	59.5 (46 to 69)	54.5 (51 to 60)	61 (56 to 74)	59 (52 to 78)
Alkaline Phosphatase (U/L)- Day14	57.5 (46 to 69)	56 (43 to 81)	53 (49 to 56)	62 (56 to 71)	60 (51 to 65.5)
Alkaline Phosphatase (U/L)- Day42	—	—	56 (53 to 59)	69 (58 to 73)	57 (51 to 68)
Alkaline Phosphatase (U/L)- Day70	54 (51 to 57)	55 (50 to 76)	—	—	—
Alkaline Phosphatase (U/L)- Day98	—	—	54 (51 to 57)	64 (54 to 77)	61 (50 to 72)
Alkaline Phosphatase (U/L)- Day140	57.5 (50 to 65)	59 (50 to 68)	—	—	—
Alkaline Phosphatase (U/L)- Day182	—	—	59.5 (52 to 61)	63 (56 to 72)	60.5 (44 to 68)
Alkaline Phosphatase (U/L)- Day238	—	—	52 (50 to 73)	61.5 (52 to 72)	58.5 (49 to 69)
Alkaline Phosphatase (U/L)- Day334	—	—	52.5 (50 to 67)	62.5 (52 to 66)	62 (50 to 67.5)
AST (U/L)- Screening	18 (16 to 20)	19 (16 to 19)	16.5 (15 to 27)	16 (14 to 19)	19 (18 to 23)
AST (U/L)- Day14	19 (16 to 22)	15 (14 to 19)	19.5 (18 to 25)	17 (14 to 20)	19 (16 to 20)
AST (U/L)- Day42	—	—	17 (13 to 20)	15 (15 to 21)	17 (16 to 20)
AST (U/L)- Day70	13 (12 to 14)	17 (15 to 19)	—	—	—
AST (U/L)- Day98	—	—	16 (16 to 20)	17 (14 to 20)	18 (16 to 21)
AST (U/L)- Day140	13.5 (12 to 15)	17 (15 to 26)	—	—	—
AST (U/L)- Day182	—	—	14.5 (12 to 16)	16 (15 to 18)	17.5 (16 to 18)
AST (U/L)- Day238	—	—	15.5 (13 to 18)	16 (14 to 18)	16 (15.5 to 22)
AST (U/L)- Day334	—	—	15.5 (14 to 24)	16 (14 to 18)	19 (15.5 to 21)
ALT (SGPT) (U/L)- Screening	22 (21 to 23)	14.5 (11 to 21)	22.5 (16 to 25)	13 (10 to 18)	16 (13 to 24)
ALT (SGPT) (U/L)- Day14	21.5 (19 to 24)	10 (8 to 19)	19.5 (16 to 30)	14 (12 to 18)	15 (12.5 to 20.5)
ALT (SGPT) (U/L)- Day42	—	—	17 (12 to 20)	14 (11 to 16)	15 (11 to 22)
ALT (SGPT) (U/L)- Day70	18 (11 to 25)	14.5 (10 to 19)	—	—	—
ALT (SGPT) (U/L)- Day98	—	—	15 (15 to 16)	14 (11 to 17)	15 (10 to 19)
ALT (SGPT) (U/L)- Day140	21 (11 to 31)	14.5 (12 to 20)	—	—	—
ALT (SGPT) (U/L)- Day182	—	—	12.5 (10 to 19)	12 (10 to 15)	15.5 (14 to 19)
ALT (SGPT) (U/L)- Day238	—	—	15.5 (11 to 19)	11.5 (11 to 15)	12.5 (9 to 22)
ALT (SGPT) (U/L)- Day334	—	—	17 (12 to 20)	13 (10 to 15)	15.5 (12 to 26.5)

PrimaryHemoglobin, Creatinine in g/dL

Laboratory results are summarized by analyte and timepoint.

Time frame:: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Reported as:: Median · g/dL

Hemoglobin, Creatinine in g/dL
g/dL	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Hemoglobin (g/dL)- Screening	14.7 (13.7 to 15.7)	13.75 (12.7 to 15.2)	13.85 (13.2 to 14.6)	14.7 (13.2 to 15)	14.8 (13.4 to 15.4)
Hemoglobin (g/dL)- Day14	14.65 (14.4 to 14.9)	13.45 (12.8 to 14.3)	13.5 (12.3 to 14.4)	13.5 (12.5 to 14.8)	13.95 (12.75 to 14.7)
Hemoglobin (g/dL)- Day42	—	—	13.9 (12.5 to 14.4)	13.8 (13.1 to 14.5)	13.8 (13.3 to 15.1)
Hemoglobin (g/dL)- Day70	13.25 (12.5 to 14)	14.1 (13 to 14.5)	—	—	—
Hemoglobin (g/dL)- Day98	—	—	13.2 (12.7 to 14.6)	14 (12.9 to 14.7)	14.8 (13.4 to 15.3)
Hemoglobin (g/dL)- Day140	14.35 (13 to 15.7)	13.65 (12.3 to 14.6)	—	—	—
Hemoglobin (g/dL)- Day182	—	—	13.6 (12.2 to 14)	13.4 (11.6 to 14.2)	14 (13.2 to 14.8)
Hemoglobin (g/dL)- Day238	—	—	13.5 (11.2 to 14.4)	13.2 (12.2 to 14)	14 (12.8 to 15.1)
Hemoglobin (g/dL)- Day334	—	—	14.25 (11.4 to 14.6)	12.75 (12.1 to 14.3)	14.15 (13.25 to 14.85)
Creatinine (g/dL)- Screening	0.00094 (0.00079 to 0.00109)	0.00077 (0.00068 to 0.00093)	0.000795 (0.00074 to 0.00091)	0.00078 (0.00068 to 0.00083)	0.0008 (0.00075 to 0.0009)
Creatinine (g/dL)- Day14	0.00102 (0.0008 to 0.00124)	0.000815 (0.00079 to 0.00092)	0.000835 (0.00077 to 0.00093)	0.00075 (0.00071 to 0.00085)	0.000835 (0.00075 to 0.00091)
Creatinine (g/dL)- Day42	—	—	0.00081 (0.00071 to 0.00099)	0.00079 (0.00071 to 0.00083)	0.00087 (0.00073 to 0.00094)
Creatinine (g/dL)- Day70	0.00088 (0.00072 to 0.00104)	0.00075 (0.0007 to 0.00096)	—	—	—
Creatinine (g/dL)- Day98	—	—	0.00083 (0.00075 to 0.0009)	0.0008 (0.0007 to 0.00086)	0.00084 (0.00075 to 0.001)
Creatinine (g/dL)- Day140	0.000935 (0.00086 to 0.00101)	0.000765 (0.00069 to 0.00095)	—	—	—
Creatinine (g/dL)- Day182	—	—	0.00085 (0.00072 to 0.00092)	0.00088 (0.00078 to 0.00094)	0.000855 (0.0008 to 0.00105)
Creatinine (g/dL)- Day238	—	—	0.000815 (0.00076 to 0.00087)	0.00076 (0.0007 to 0.00082)	0.000845 (0.00076 to 0.00092)
Creatinine (g/dL)- Day334	—	—	0.00082 (0.00076 to 0.00104)	0.00081 (0.0007 to 0.00088)	0.000895 (0.0008 to 0.00097)

PrimaryWBC, Platelets, Lymphocytes, Neutrophils in Thousand Cells/Cubic mm

Laboratory results are summarized by analyte and timepoint.

Time frame:: Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B
Reported as:: Median · thousand cells/cubic mm

WBC, Platelets, Lymphocytes, Neutrophils in Thousand Cells/Cubic mm
thousand cells/cubic mm	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
WBC (1000/cubic mm)- Screening	5.1 (4.4 to 5.8)	6.305 (4.8 to 7.3)	5.9 (5.3 to 6.2)	5.7 (5.2 to 7.1)	6.4 (5.5 to 7.4)
WBC (1000/cubic mm)- Day14	4.35 (3.4 to 5.3)	5.62 (4.4 to 7.5)	5.65 (4.8 to 6.6)	6 (5.6 to 6.8)	6.4 (5.185 to 6.85)
WBC (1000/cubic mm)- Day42	—	—	6.45 (5.4 to 8.3)	6.2 (5.1 to 7.1)	6.3 (5.3 to 6.9)
WBC (1000/cubic mm)- Day70	5.8 (3.6 to 8)	6.12 (5.6 to 7.3)	—	—	—
WBC (1000/cubic mm)- Day98	—	—	5.8 (5.6 to 6)	6.11 (5.3 to 7.1)	5.7 (4.8 to 6.7)
WBC (1000/cubic mm)- Day140	4.15 (4.1 to 4.2)	6.26 (4.9 to 9.1)	—	—	—
WBC (1000/cubic mm)- Day182	—	—	6 (5.4 to 6.6)	5.6 (5.1 to 7.1)	6.25 (5 to 7)
WBC (1000/cubic mm)- Day238	—	—	6 (4.8 to 6.2)	6 (5 to 7)	6.15 (5.57 to 6.75)
WBC (1000/cubic mm)- Day334	—	—	5.4 (5 to 6.2)	5.6 (5.01 to 6.7)	5.88 (5.25 to 6.65)
Platelets (1000/cubic mm)- Screening	288 (236 to 340)	296 (266.9 to 341)	229 (217 to 387)	250 (212 to 295)	246 (210 to 273)
Platelets (1000/cubic mm)- Day14	297 (205 to 389)	297.5 (259 to 323)	236 (210 to 328)	244 (205 to 277)	226.5 (201.55 to 278.5)
Platelets (1000/cubic mm)- Day42	—	—	238 (207 to 334)	243 (209 to 313)	260.5 (193 to 291)
Platelets (1000/cubic mm)- Day70	277.5 (243 to 312)	286 (266 to 308)	—	—	—
Platelets (1000/cubic mm)- Day98	—	—	223 (203 to 256)	244 (193 to 311)	224 (191.1 to 268)
Platelets (1000/cubic mm)- Day140	264.5 (243 to 286)	287 (274 to 304)	—	—	—
Platelets (1000/cubic mm)- Day182	—	—	215.5 (205 to 328)	278 (201 to 362.6)	232 (190 to 287)
Platelets (1000/cubic mm)- Day238	—	—	234.5 (210 to 315)	266.1 (229 to 336)	239.8 (188 to 287.9)
Platelets (1000/cubic mm)- Day334	—	—	253.5 (197 to 339)	280 (218 to 347)	239.05 (192 to 273.5)
Lymphocytes (1000/cubic mm)- Screening	2.189 (1.148 to 3.23)	1.942 (1.579 to 2.403)	1.7635 (1.63 to 1.911)	1.918 (1.664 to 2.213)	2.134 (1.863 to 2.28)
Lymphocytes (1000/cubic mm)- Day14	2.037 (1.054 to 3.02)	1.7895 (1.452 to 2.001)	1.8115 (1.613 to 1.876)	1.848 (1.56 to 2.237)	1.935 (1.6725 to 2.1865)
Lymphocytes (1000/cubic mm)- Day42	—	—	1.583 (1.361 to 1.879)	1.85 (1.415 to 2.313)	1.93 (1.742 to 2.144)
Lymphocytes (1000/cubic mm)- Day70	2.0955 (1.051 to 3.14)	2.1495 (1.712 to 2.467)	—	—	—
Lymphocytes (1000/cubic mm)- Day98	—	—	1.589 (1.534 to 1.773)	1.8 (1.461 to 2.081)	1.98 (1.6 to 2.165)
Lymphocytes (1000/cubic mm)- Day140	1.574 (1.168 to 1.98)	1.9625 (1.486 to 2.75)	—	—	—
Lymphocytes (1000/cubic mm)- Day182	—	—	1.659 (1.507 to 1.822)	2.076 (1.501 to 2.421)	1.945 (1.591 to 2.19)
Lymphocytes (1000/cubic mm)- Day238	—	—	1.679 (1.535 to 1.959)	1.928 (1.78 to 2.057)	1.6865 (1.504 to 1.8315)
Lymphocytes (1000/cubic mm)- Day334	—	—	1.5425 (1.465 to 1.795)	1.96 (1.48 to 2.25)	1.745 (1.587 to 1.97)
Neutrophils (1000/cubic mm)- Screening	2.22 (1.862 to 2.578)	3.848 (2.875 to 5.313)	3.568 (3.403 to 3.837)	3.648 (2.77 to 4.023)	3.41 (2.965 to 4.788)
Neutrophils (1000/cubic mm)- Day14	1.7345 (1.635 to 1.834)	3.322 (2.411 to 5.1)	3.2585 (2.41 to 4)	3.397 (3.144 to 4.141)	3.4945 (2.405 to 4.112)
Neutrophils (1000/cubic mm)- Day42	—	—	3.7595 (3.375 to 6.01)	3.66 (2.885 to 4.509)	3.317 (2.945 to 3.95)
Neutrophils (1000/cubic mm)- Day70	3.072 (1.904 to 4.24)	3.9035 (3.161 to 4.417)	—	—	—
Neutrophils (1000/cubic mm)- Day98	—	—	3.492 (3.27 to 3.578)	3.67 (2.749 to 4.303)	3.101 (2.235 to 4.541)
Neutrophils (1000/cubic mm)- Day140	2.01 (1.681 to 2.339)	3.7175 (3.034 to 4.869)	—	—	—
Neutrophils (1000/cubic mm)- Day182	—	—	3.821 (3.278 to 4.284)	3.264 (2.301 to 4.09)	3.684 (2.86 to 4.14)
Neutrophils (1000/cubic mm)- Day238	—	—	3.349 (2.832 to 3.886)	3.413 (2.57 to 4.074)	3.9935 (3.1115 to 4.3735)
Neutrophils (1000/cubic mm)- Day334	—	—	3.3185 (2.85 to 3.559)	3.135 (2.41 to 4.235)	3.395 (2.7725 to 4.2395)

PrimaryNumber of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation

From the study product discontinuation form, study product administration reasons are tabulated by treatment arm

Time frame:: Measured through study completion, up to 31 months
Reported as:: Count of participants · Participants

Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
Participants	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Adverse Experience	0	0	0	0	1
Reactogenicity Symptom	0	0	0	1	0
Unable to Contact/Out of Window	0	0	0	0	5
Participant Refused Vaccination	0	0	0	1	1
No Discontinuation	2	10	6	19	14

SecondaryOccurrence of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500.

Time frame:: Measured at Month 2.5 for part A and 8.5 for part B
Reported as:: Count of participants · Participants

Occurrence of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination
Participants	Part A: Vaccine	Part B: Vaccine 1	Part B: Vaccine 2
254008_D11gp120.avi/293F	8	18	13
51802_D11gp120.avi/293F	9	18	13
A244 D11gp120_avi	8	18	13
B.6240_D11gp120/293F	9	17	13
BJOX002_D11gp120.avi/293F	9	16	12
BORI_D11gp120.avi/293F	9	15	11
CNE20_D11gp120.avi/293F	8	18	13
TT31P.2792_D11gp120.avi/293F	8	18	13
gp120-A	8	18	12
gp120-AE	9	17	13
gp120-B	9	18	11
gp120-C	9	17	12
gp70-001428.2.42 V1V2	6	17	11
gp70-191084_B7 V1V2	9	17	11
gp70-62357.14 V1V2	5	14	9
gp70-700010058 V1V2	1	15	11
gp70-7060101641 V1V2	6	17	10
gp70-96ZM651.02 V1v2	8	16	11
gp70-BF1266_431a_V1V2	5	17	8
gp70-BJOX002000.03.2 V1V2	8	17	11
gp70-C2101.c01_V1V2	6	17	11
gp70-CAP210.2.00.E8 V1V2	6	16	8
gp70-CM244.ec1 V1V2	8	18	11
gp70-Ce1086_B2 V1V2	8	18	13
gp70-RHPA4259.7 V1V2	5	16	8
gp70-TT31P.2F10.2792 V1V2	4	13	9
gp70-TV1.21 V1V2	7	17	9
gp70_B.CaseA_V1_V2	6	17	11

SecondaryLevels of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 12).

Time frame:: Measured at Month 2.5 for part A and 8.5 for part B
Reported as:: Median · relative fluorescence units

Levels of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination
relative fluorescence units	Part A: Vaccine	Part B: Vaccine 1	Part B: Vaccine 2
254008_D11gp120.avi/293F	22000 (22000 to 22000)	22000 (22000 to 22000)	22000 (22000 to 22000)
51802_D11gp120.avi/293F	13847.8 (13546.5 to 22000)	22000 (16922.6 to 22000)	12427.5 (6267.8 to 22000)
A244 D11gp120_avi	22000 (22000 to 22000)	22000 (22000 to 22000)	22000 (22000 to 22000)
B.6240_D11gp120/293F	12265 (9028.5 to 18413.5)	22000 (18193.8 to 22000)	22000 (13876.8 to 22000)
BJOX002_D11gp120.avi/293F	11645.2 (8450.2 to 15975.5)	22000 (19076.4 to 22000)	14547.1 (9620.1 to 21372.2)
BORI_D11gp120.avi/293F	5944.5 (3552 to 8805.8)	16031.8 (10413.1 to 20097)	7429.2 (5766.5 to 12648.8)
CNE20_D11gp120.avi/293F	22000 (22000 to 22000)	22000 (22000 to 22000)	22000 (22000 to 22000)
TT31P.2792_D11gp120.avi/293F	22000 (22000 to 22000)	22000 (22000 to 22000)	22000 (22000 to 22000)
gp120-A	13589.6 (10025.8 to 18696.2)	22000 (17859 to 22000)	18287.8 (11116.1 to 21526.8)
gp120-AE	11629.5 (8498.8 to 13170.2)	18609 (16413.8 to 22000)	11534.5 (9247.5 to 19902.2)
gp120-B	3895.2 (3754 to 8448.8)	10957.1 (8435.3 to 16405.2)	13483 (8970.9 to 19446.6)
gp120-C	12084.8 (9242.8 to 17222)	22000 (18300 to 22000)	15846.6 (11677.2 to 22000)
gp70-001428.2.42 V1V2	4214.6 (1287.6 to 6912.2)	3180 (1325.5 to 8855.8)	7208.8 (3152.6 to 14312.9)
gp70-191084_B7 V1V2	14985 (942 to 18635.2)	21866.8 (13914.5 to 22000)	21177.8 (10583.2 to 22000)
gp70-62357.14 V1V2	764.8 (247.8 to 3565.2)	1399.8 (1077.1 to 3775.1)	2140.8 (1302 to 3711.5)
gp70-700010058 V1V2	3103 (3103 to 3103)	2172.2 (396.2 to 6597.9)	11938.2 (3265.8 to 22000)
gp70-7060101641 V1V2	402.6 (289.4 to 2538.8)	1176.2 (842.5 to 2095.5)	1217.4 (681.6 to 2033.7)
gp70-96ZM651.02 V1v2	10010.6 (300.6 to 21457.8)	12543.9 (8143.1 to 22000)	11192.5 (6121.4 to 20222.1)
gp70-BF1266_431a_V1V2	808 (560.2 to 5568.8)	3456 (641 to 9020.8)	2003.5 (1455.2 to 3187.4)
gp70-BJOX002000.03.2 V1V2	6452.2 (1076.9 to 11295.9)	17549.8 (6772.8 to 22000)	7962.2 (4547.6 to 15902.6)
gp70-C2101.c01_V1V2	14362 (5960.7 to 20792.3)	11920.5 (6894 to 22000)	7065.8 (2127.5 to 18989.5)
gp70-CAP210.2.00.E8 V1V2	1596.2 (494.2 to 4094.9)	1571.4 (487.8 to 5566.1)	1641 (1030.9 to 2463.3)
gp70-CM244.ec1 V1V2	22000 (18385.9 to 22000)	22000 (22000 to 22000)	22000 (13074.6 to 22000)
gp70-Ce1086_B2 V1V2	22000 (22000 to 22000)	22000 (22000 to 22000)	22000 (10914.2 to 22000)
gp70-RHPA4259.7 V1V2	782.5 (766.2 to 3177.2)	2845.1 (1565.3 to 5682.8)	1575.6 (1293.6 to 2538.4)
gp70-TT31P.2F10.2792 V1V2	2308.4 (568.4 to 4841.8)	1821.8 (1275.2 to 5421.5)	1712.5 (1117.5 to 2679)
gp70-TV1.21 V1V2	1249.8 (727.8 to 6326.6)	3075.2 (636.5 to 8293.8)	2528.5 (1957 to 3612.8)
gp70_B.CaseA_V1_V2	1177 (613.9 to 5457.7)	4071 (2531 to 10252.8)	4955.8 (1717.6 to 13117.4)

SecondaryBreadth of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. Magnitude-breadth (MB) curves characterized the magnitude (Binding antibody MFI\* at 1:50 dilution and titer) and breadth (number of antigens with positive response at given MFI\* or titer) of each individual plasma sample assayed against a panel of antigens. The x-axis represents the response magnitude and the y-axis represents the fraction of antigens with response magnitude greater than the x-axis value. In addition to the individual sample specific curves, the group-specific curve displayed the average MB across all participants in that group. The area-under-the-magnitude-breadth curve (AUC-MB) was calculated as the average of the log10 MFI\* (log10 titer) over the panel of antigens.

Time frame:: Measured at Month 2.5 for part A and 8.5 for part B
Reported as:: Median · log10 titer* proportion of antigens

Breadth of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination
log10 titer* proportion of antigens	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
gp120 Breadth Panel	2 (2 to 2)	4 (3.9 to 4.1)	2 (2 to 2)	4.2 (4.1 to 4.4)	4 (3.4 to 4.1)
gp70 V1V2 Breadth Panel	2 (2 to 2)	2.7 (2.5 to 3.1)	2 (2 to 2)	3.3 (3 to 3.6)	3.2 (2.3 to 3.5)

SecondaryPart B: Occurrence of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination

Neutralizing antibodies against HIV1were measured as a function of reductions in Tat-regulatedluciferase (Luc) reporter gene expression in TZM-blcells. The assay performed in TZM-bl cells measured neutralization titers against a panel of Env-pseudotyped viruses that exhibit the following naturalization phenotypes. Response to a virus/isolate was considered positive if the neutralization titer was above a prespecified cutoff. A titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (ID50 and ID80, cells only). The prespecified cutoff was 20 for MW965.26 (Tier 1a) and 10 for other viruses.

Time frame:: Measured at Month 8.5 for part B only
Reported as:: Count of participants · Participants

Part B: Occurrence of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination
Participants	Part B: Vaccine 1	Part B: Vaccine 2
MW965.26 (ID50)	16	15
1056-10.TA11.1826 (ID50)	0	0
6535.3 (ID50)	0	0
Bx08.16 (ID50)	3	0
Q23.17 (ID50)	0	0
ZM197M.PB7 (ID50)	0	0
92UG037.1 (ID50)	0	2
JR-FL (ID50)	0	0
MW965.26 (ID80)	16	14
1056-10.TA11.1826 (ID80)	0	0
6535.3 (ID80)	0	0
Bx08.16 (ID80)	0	0
Q23.17 (ID80)	0	0
ZM197M.PB7 (ID80)	0	0
92UG037.1 (ID80)	0	0
JR-FL (ID80)	0	0

SecondaryPart B: Levels of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination

Time frame:: Measured at Month 8.5 for part B only
Reported as:: Median · Titers

Part B: Levels of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination
Titers	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
MW965.26 (ID50)	10 (10 to 10)	681.2 (327.4 to 906.1)	583.5 (227.2 to 1306.6)
1056-10.TA11.1826 (ID50)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
6535.3 (ID50)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
Bx08.16 (ID50)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
Q23.17 (ID50)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
ZM197M.PB7 (ID50)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
92UG037.1 (ID50)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
JR-FL (ID50)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
MW965.26 (ID80)	10 (10 to 10)	233.7 (100.9 to 331)	181 (74.2 to 426.3)
1056-10.TA11.1826 (ID80)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
6535.3 (ID80)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
Bx08.16 (ID80)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
Q23.17 (ID80)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
ZM197M.PB7 (ID80)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
92UG037.1 (ID80)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
JR-FL (ID80)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)

SecondaryBreadth of gp70-V1V2 IgG and gp120 IgA, Assessed by Binding Antibody Multiplex Assay, and ADCC Activities Against HIV-1 Subtypes A, B, C and A/E Two Weeks After the Last Vaccination in Part B

For Binding Antibody Multiplex Assay, gp70-V1V2 IgG, the area-under-the-magnitude-breadth curve (AUC-MB) was calculated as the average of the log10 MFI\* (log10 titer) over the panel of antigens. For ADCC GranToxiLux, AUC-MB was calculated as the average of the AUC over the panel of antigens, where AUC is defined as nonparametric area under the net percent granzyme B activity vs log10 (dilution) curve ("AUC"), calculated using the trapezoidal rule, and setting any net percent granzyme B activity below 0% to 0%. For ADCC Luciferase, (AUC-MB) was calculated as the average of the pAUC over the panel of antigens, where pAUC is defined as nonparametric partial area under the baseline subtracted curves ("pAUC"), calculated using the trapezoidal rule on the first four dilutions of the baseline subtracted curves, setting baseline subtracted loss Luciferase activity less than 0% to zero.

Time frame:: Measured at Month 8.5 for part B only
Reported as:: Median · log10 titer* proportion of antigens

Breadth of gp70-V1V2 IgG and gp120 IgA, Assessed by Binding Antibody Multiplex Assay, and ADCC Activities Against HIV-1 Subtypes A, B, C and A/E Two Weeks After the Last Vaccination in Part B
log10 titer* proportion of antigens	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
ADCC GranToxiLux against HIV-1 subtypes A, B, C and A/E	0.2 (0.1 to 0.6)	19 (13.9 to 25)	11.4 (7.1 to 16.3)
ADCC Luciferase against HIV-1 subtypes A, B, C and A/E	2.2 (1.3 to 2.9)	31.8 (19.3 to 45.8)	17.8 (10.5 to 28.7)
gp70 V1V2 IgG	2 (2 to 2)	3.3 (3 to 3.6)	3.2 (2.3 to 3.5)

SecondaryOccurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.

PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value \<=0.00001. Please note the above analyses were applied by the lab to determine the response positivity, not the planned analyses for the study outcome measures. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.

Time frame:: Measured at Month 8.5 for part B only
Reported as:: Count of participants · Participants

Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.
Participants	Part B: Vaccine 1	Part B: Vaccine 2
ANY ENV PTEG	19	7
ANY GAG PTEG	1	0
ENV-1-PTEG-SEQ	17	7
ENV-2-PTEG-SEQ	16	4
GAG-1-PTEG-SEQ	0	0
GAG-2-PTEG-SEQ	1	0

SecondaryLevel of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.

Time frame:: Measured at Month 8.5 for part B only
Reported as:: Median · % CD4+ T-cells

Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.
% CD4+ T-cells	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
ANY ENV PTEG	-0.011 (-0.015 to -0.008)	0.313 (0.183 to 0.386)	0.102 (0.053 to 0.236)
ANY GAG PTEG	-0.001 (-0.007 to 0.003)	0.017 (-0.004 to 0.028)	0.001 (-0.006 to 0.009)
ENV-1-PTEG-SEQ	-0.005 (-0.009 to -0.003)	0.166 (0.1 to 0.209)	0.052 (0.026 to 0.131)
ENV-2-PTEG-SEQ	-0.007 (-0.01 to -0.004)	0.142 (0.064 to 0.194)	0.037 (0.019 to 0.058)
GAG-1-PTEG-SEQ	-0.001 (-0.003 to 0.003)	0.004 (-0.004 to 0.018)	-0.002 (-0.008 to 0.005)
GAG-2-PTEG-SEQ	-0.002 (-0.004 to 0.001)	0.009 (0 to 0.017)	0.003 (-0.002 to 0.006)

SecondaryOccurrence of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.

Time frame:: Measured at Month 8.5 for part B only
Reported as:: Count of participants · Participants

Occurrence of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.
Participants	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
ANY ENV PTEG	0	0	0
ANY GAG PTEG	0	0	0
ENV-1-PTEG-SEQ	0	0	0
ENV-2-PTEG-SEQ	0	0	0
GAG-1-PTEG-SEQ	0	0	0
GAG-2-PTEG-SEQ	0	0	0

SecondaryLevel of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.

Time frame:: Measured at Month 8.5 for part B only
Reported as:: Median · % CD8+ T-cells

Level of CD8+ T Cell Responses to the HIV Proteins Included in the Vaccine Two Weeks After the Last Vaccination. Measured by Flow Cytometry.
% CD8+ T-cells	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
ANY ENV PTEG	-0.003 (-0.008 to 0.004)	0.007 (-0.002 to 0.013)	-0.007 (-0.012 to 0)
ANY GAG PTEG	0.002 (-0.011 to 0.003)	-0.006 (-0.009 to 0.002)	-0.004 (-0.013 to -0.001)
ENV-1-PTEG-SEQ	0.001 (-0.003 to 0.004)	0.006 (-0.001 to 0.017)	-0.002 (-0.007 to 0.002)
ENV-2-PTEG-SEQ	-0.002 (-0.007 to 0)	0 (-0.008 to 0.007)	-0.004 (-0.006 to 0)
GAG-1-PTEG-SEQ	0.002 (-0.009 to 0.007)	0 (-0.004 to 0.002)	-0.005 (-0.009 to 0)
GAG-2-PTEG-SEQ	0 (-0.003 to 0.001)	-0.004 (-0.007 to 0)	0 (-0.005 to 0.002)

Adverse events

Collected over Serious Adverse events are collected throughout the study (months 0-8 for Part A, and months 0-14 for Part B). Non-serious adverse events are collected through 30 days after each vaccination (at months 0,2 for Part A, and months 0, 1, 3, 6, 8 for Part B).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part A: Placebo	0/2 (0%)	0/2 (0%)	2/2 (100%)
Part A: Vaccine	0/10 (0%)	0/10 (0%)	6/10 (60%)
Part B: Placebo	0/6 (0%)	0/6 (0%)	5/6 (83.3%)
Part B: Vaccine 1	0/21 (0%)	0/21 (0%)	19/21 (90.5%)
Part B: Vaccine 2	0/21 (0%)	0/21 (0%)	18/21 (85.7%)

Most frequent other events

Showing 10 of 101

Most frequent other events
Event	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2
Any Event in SOCGastrointestinal disorders	0/2	1/10	4/6	5/21	3/21
Any Event in SOCInfections and infestations	0/2	3/10	3/6	10/21	13/21
Any Event in SOCInjury, poisoning and procedural complications	1/2	1/10	1/6	3/21	0/21
Procedural painInjury, poisoning and procedural complications	1/2	0/10	0/6	0/21	0/21
Any Event in SOCNervous system disorders	1/2	0/10	0/6	2/21	1/21
Tardive dyskinesiaNervous system disorders	1/2	0/10	0/6	0/21	0/21
Any Event in SOCRespiratory, thoracic and mediastinal disorders	1/2	0/10	0/6	1/21	3/21
Upper-airway cough syndromeRespiratory, thoracic and mediastinal disorders	1/2	0/10	0/6	0/21	0/21
Any Event in SOCSkin and subcutaneous tissue disorders	1/2	1/10	1/6	4/21	5/21
RashSkin and subcutaneous tissue disorders	1/2	0/10	0/6	1/21	0/21

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2	Total
Median	36.5 (26 to 47)	22.5 (18 to 47)	29 (27 to 36)	25 (19 to 40)	31 (21 to 48)	26.5 (18 to 48)

Age, Customized
Age, Customized(Participants)	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2	Total
Less than 18 years	0	0	0	0	0	0
18 - 20 years	0	4	0	3	0	7
21 - 30 years	1	3	4	12	10	30
31 - 40 years	0	1	2	6	9	18
41 - 50 years	1	2	0	0	2	5
Above 50 years	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2	Total
Female	1	6	3	13	11	34
Male	1	4	3	8	10	26

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2	Total
Hispanic or Latino	0	0	0	1	1	2
Not Hispanic or Latino	2	10	6	20	20	58
Unknown or Not Reported	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2	Total
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	2	0	2	2	6
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	1	0	1	3	0	5
White	1	7	4	14	17	43
More than one race	0	1	1	2	1	5
Unknown or Not Reported	0	0	0	0	1	1

Region of Enrollment
Region of Enrollment(Participants)	Part A: Placebo	Part A: Vaccine	Part B: Placebo	Part B: Vaccine 1	Part B: Vaccine 2	Total
USA	2	10	6	21	21	60

Study locations

6 sites

Alabama CRS
Birmingham, Alabama 35294, United States
The Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia 30030, United States
Fenway Health (FH) CRS
Boston, Massachusetts 02215-4302, United States
University of Rochester Vaccines to Prevent HIV Infection CRS
Rochester, New York 14642, United States
Case Clinical Research Site
Cleveland, Ohio 44106, United States
Penn Prevention CRS
Philadelphia, Pennsylvania 19104, United States

References and documents

Study documents

Study protocol · Sep 28, 2017
Statistical analysis plan · Jan 25, 2021

Documents are hosted by the registry — open the source record to download them.

Registry details

Key details

Study ID: NCT03409276
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party: Sponsor
First posted: Jan 24, 2018
Start date: Mar 16, 2018
Primary completion: May 11, 2020
Completion: Oct 22, 2020
Results posted: Apr 25, 2022
Last update: Apr 25, 2022

Study contacts

Ian Frank

study chair · University of Pennsylvania

Turner Overton

study chair · University of Alabama at Birmingham

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

HIV Infections→

Other studies from this sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Start the discussion

Evaluating the Safety and Immunogenicity of Env (A,B,C,A/E)/Gag (C) DNA and gp120 (A,B,C,A/E) Protein/GLA-SE HIV Vaccines, Given Individually or Co-administered, in Healthy, HIV-1-Uninfected Adults

Study summary

Conditions studied

Browse trials for

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

References and documents

Study documents

Registry details

Key details

Study contacts

Oversight

Not currently enrolling

Follow this study

Discussion

Other studies in this condition

Other studies from this sponsor

Inclusion criteria

Exclusion criteria