Evaluating the Safety and Immunogenicity of ALVAC-HIV and MF59®- or AS01B-adjuvanted Bivalent Subtype C gp120 in Healthy, HIV-uninfected Adult Participants

NCT ID: NCT03122223

Last Updated: 2023-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-16
• Study Completion Date: 2020-07-30

Brief Summary

A phase 1/2a clinical trial to evaluate the safety and immunogenicity of ALVAC-HIV (vCP2438) and of MF59®- or AS01B-adjuvanted clade C Env protein, in healthy, HIV-uninfected adult participants

Detailed Description

The primary objective of this study is to evaluate the safety and tolerability of ALVAC-HIV and bivalent gp120 protein/MF59 or bivalent gp120 protein/AS01(B). This study will also compare HIV-specific CD4+ T-cell response rates at the Month 6.5 timepoint (2 weeks after the fourth vaccination) of ALVAC-HIV and bivalent gp120 protein/MF59 to each of the bivalent gp120 protein/AS01(B) vaccine regimens. Additionally, this study will compare HIV-specific Env-gp120 binding antibody response magnitudes at the Month 12 timepoint (6 months after the fourth vaccination) of ALVAC-HIV and bivalent gp120 protein/MF59 to each of the bivalent gp120 protein/AS01(B) vaccine regimens.

The study will enroll 160 healthy, HIV-uninfected volunteers aged 18 to 40 years. Groups 1 to 3 will consist of a total of 150 participants who will receive the vaccines at Months 0, 1, 3, and 6, while 10 participants in Group 4 will receive placebos at Months 0, 1, 3, 6.

Study visits will include a physical examination, an interview and/or questionnaire, HIV testing and HIV risk-reduction counseling, and urine and blood collection. Participants may optionally choose to provide rectal fluid, cervical fluid, semen, and/or stool samples.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

ALVAC-HIV + 100mcg Protein/MF59 + Placebo

50 participants will receive 1 mL ALVAC-HIV injection in the left deltoid on Months 0, 1, 3, and 6. They will receive 0.5 mL100 mcg Protein/MF59 and 0.75 mL placebo injection in the right deltoid on Months 3 and 6.

Group Type: ACTIVE_COMPARATOR

ALVAC-HIV (vCP2438)

Intervention Type: BIOLOGICAL

expresses the gene products 96ZM651 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane anchor (TM) sequence of gp41 (28 amino acids clade B LAI strain) and Gag and Pro (clade B LAI strain). It is formulated as a lyophilized vaccine for injection at a viral titer greater than or equal to 1 × 10\^6 cell culture infectious dose (CCID)50 and less than 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and is reconstituted with 1 mL of sterile sodium chloride solution (NaCl 0.4%), administered IM as a single 1 mL dose.

Bivalent subtype C gp120/MF59

Intervention Type: BIOLOGICAL

clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant, administered IM as a single 0.5 mL dose.

Placebo

Intervention Type: BIOLOGICAL

Sodium Chloride for Injection, 0.9%, administered IM.

ALVAC-HIV + 100mcg Protein/AS01(B) + Placebo

50 participants will receive 1 mL ALVAC-HIV injection in the left deltoid on Months 0, 1, 3, and 6. They will receive 0.75 mL100 mcg Protein/AS01(B) and 0.5 mL placebo injection in the right deltoid on Months 3 and 6.

Group Type: ACTIVE_COMPARATOR

ALVAC-HIV (vCP2438)

Intervention Type: BIOLOGICAL

expresses the gene products 96ZM651 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane anchor (TM) sequence of gp41 (28 amino acids clade B LAI strain) and Gag and Pro (clade B LAI strain). It is formulated as a lyophilized vaccine for injection at a viral titer greater than or equal to 1 × 10\^6 cell culture infectious dose (CCID)50 and less than 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and is reconstituted with 1 mL of sterile sodium chloride solution (NaCl 0.4%), administered IM as a single 1 mL dose.

Bivalent subtype C gp120/AS01(B)

Intervention Type: BIOLOGICAL

clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 20 mcg or 100 mcg, mixed with AS01B adjuvant, administered IM as a single 0.75 mL dose.

Placebo

Intervention Type: BIOLOGICAL

Sodium Chloride for Injection, 0.9%, administered IM.

ALVAC-HIV + 20mcg Protein/AS01(B) + Placebo

50 participants will receive 1 mL ALVAC-HIV injection in the left deltoid on Months 0, 1, 3, and 6. They will receive 0.75 mL 20 mcg Protein/AS01(B) and 0.5 mL placebo injection in the right deltoid on Months 3 and 6.

Group Type: ACTIVE_COMPARATOR

ALVAC-HIV (vCP2438)

Intervention Type: BIOLOGICAL

expresses the gene products 96ZM651 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane anchor (TM) sequence of gp41 (28 amino acids clade B LAI strain) and Gag and Pro (clade B LAI strain). It is formulated as a lyophilized vaccine for injection at a viral titer greater than or equal to 1 × 10\^6 cell culture infectious dose (CCID)50 and less than 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and is reconstituted with 1 mL of sterile sodium chloride solution (NaCl 0.4%), administered IM as a single 1 mL dose.

Bivalent subtype C gp120/AS01(B)

Intervention Type: BIOLOGICAL

clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 20 mcg or 100 mcg, mixed with AS01B adjuvant, administered IM as a single 0.75 mL dose.

Placebo

Intervention Type: BIOLOGICAL

Sodium Chloride for Injection, 0.9%, administered IM.

Placebo

10 participants will receive 1 mL of the placebo injection in the left deltoid on Months 0, 1, 3, and 6. They will receive 0.5 mL of the placebo injection and 0.75 mL of a separate placebo injection in the right deltoid on Months 3 and 6.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Sodium Chloride for Injection, 0.9%, administered IM.

Interventions

ALVAC-HIV (vCP2438)

expresses the gene products 96ZM651 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane anchor (TM) sequence of gp41 (28 amino acids clade B LAI strain) and Gag and Pro (clade B LAI strain). It is formulated as a lyophilized vaccine for injection at a viral titer greater than or equal to 1 × 10\^6 cell culture infectious dose (CCID)50 and less than 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and is reconstituted with 1 mL of sterile sodium chloride solution (NaCl 0.4%), administered IM as a single 1 mL dose.

Intervention Type: BIOLOGICAL

Bivalent subtype C gp120/MF59

clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant, administered IM as a single 0.5 mL dose.

Intervention Type: BIOLOGICAL

Bivalent subtype C gp120/AS01(B)

clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 20 mcg or 100 mcg, mixed with AS01B adjuvant, administered IM as a single 0.75 mL dose.

Intervention Type: BIOLOGICAL

Placebo

Sodium Chloride for Injection, 0.9%, administered IM.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

General and Demographic Criteria:

• Age of 18 to 40 years
• Access to a participating 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; provides answers to a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent before the last required clinic visit
• 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 (see the study protocol for more information about low risk guidelines).

Laboratory Inclusion Values:

Hemogram/Complete Blood Count (CBC):

• Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were assigned female sex at birth, greater than or equal to 13.0 g/dL for volunteers who were assigned male sex at birth. For transgender participants who have been on hormone therapy for more than 6 consecutive months, determine hemoglobin eligibility based on the gender with which they identify (ie, a transgender female who has been on hormone therapy for more than 6 consecutive months should be assessed for eligibility using the hemoglobin parameters for persons assigned female sex at birth).
• 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 to 550,000/mm^3

Chemistry:

• Chemistry panel: ALT, AST, and ALP 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 FDA-approved enzyme immunoassay (EIA). Non-US sites may use locally available assays that have been approved by HVTN Laboratory Operations.
• 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 assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin 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: Africa - A volunteer who was assigned female sex at birth must:

• Agree to consistently use effective contraception (see the study protocol for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception for participants in Africa is defined as using 2 methods of birth control. These include 1 of the following methods:

• Condoms (male or female), or
• Diaphragm or cervical cap, PLUS 1 of the following methods:
• Intrauterine device (IUD),
• Hormonal contraception (in accordance with applicable national contraception guidelines),
• Successful vasectomy in any partner assigned male at birth (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 after vasectomy); or
• Any other contraceptive method approved by the HVTN 120 Protocol Safety Review Team (PSRT)
• 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.
• Reproductive status: United States - A volunteer who was assigned female sex at birth must:

• Agree to consistently use effective contraception (see the study protocol for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception for participants in the United States is defined as using any 1 or more of the following methods of birth control:

• Condoms (male or female) with or without spermicide,
• Diaphragm or cervical cap with spermicide,
• Intrauterine device (IUD),
• Hormonal contraception, or
• Successful vasectomy in any partner assigned male at birth (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 after vasectomy); or
• Any other contraceptive method approved by the HVTN 120 PSRT
• Or must 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 must be sexually abstinent.
• Volunteers who were assigned female sex at birth 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

Other:

• Volunteers 21 years of age and older who were assigned female sex at birth consenting to provide cervical samples:

• Pap smear within:

• the 3 years prior to enrollment with the latest result reported as normal or ASCUS (atypical squamous cells of undetermined significance), OR
• the 5 years prior to enrollment, with the latest result reported as normal, or ASCUS with no evidence of high risk HPV.
• If no pap smear was done within the last 3 years prior to enrollment (or within the last 5 years, if high risk HPV testing was performed), the volunteer must be willing to undergo a pap smear with the result reported as normal or ASCUS prior to sample collection.

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: 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 120 study
• Pregnant or breastfeeding
• Active duty and reserve U.S. 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 120 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 120 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 for vaccines that have subsequently undergone licensure. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 120 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) more than 5 years ago, eligibility for enrollment will be determined by the HVTN 120 PSRT on a case-by-case basis.
• Live attenuated vaccines received within 30 days before first study vaccination or scheduled within 14 days after first study vaccination (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine)
• Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first study vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
• Allergy treatment with antigen injections within 30 days before first study vaccination or that are scheduled within 14 days after first study vaccination

Immune System:

• Immunosuppressive medications received within 168 days before first study 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 or equal to 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 such as eggs, egg products, or neomycin, 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 study vaccination (for mAb see criterion above)
• Autoimmune disease
• Immunodeficiency

Clinically Significant Medical Conditions:

• 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 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 other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent US 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. (Not excluded: type 2 cases controlled with diet alone or a 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 3 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Sanofi Pasteur, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Z Mike Chirenje

Role: STUDY_CHAIR

UZ-UCSF Collaborative Research Program

Locations

Bridge HIV CRS

San Francisco, California, United States

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, United States

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, United States

Fenway Health (FH) CRS

Boston, Massachusetts, United States

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, United States

Case Clinical Research Site

Cleveland, Ohio, United States

Penn Prevention CRS

Philadelphia, Pennsylvania, United States

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, United States

Seattle Vaccine and Prevention CRS

Seattle, Washington, United States

National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS

Mbeya, , Tanzania

Matero Reference Clinic CRS

Lusaka, , Zambia

Seke South CRS

Chitungwiza, , Zimbabwe

Countries

United States; Tanzania; Zambia; Zimbabwe

References

Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.

Reference Type: DERIVED

PMID: 40190112 (View on PubMed)

Chirenje ZM, Laher F, Dintwe O, Muyoyeta M, deCamp AC, He Z, Grunenberg N, Laher Omar F, Seaton KE, Polakowski L, Woodward Davis AS, Maganga L, Baden LR, Mayer K, Kalams S, Keefer M, Edupuganti S, Rodriguez B, Frank I, Scott H, Stranix-Chibanda L, Gurunathan S, Koutsoukos M, Van Der Meeren O, DiazGranados CA, Paez C, Andersen-Nissen E, Kublin J, Corey L, Ferrari G, Tomaras G, McElrath MJ. Protein Dose-Sparing Effect of AS01B Adjuvant in a Randomized Preventive HIV Vaccine Trial of ALVAC-HIV (vCP2438) and Adjuvanted Bivalent Subtype C gp120. J Infect Dis. 2024 Aug 16;230(2):e405-e415. doi: 10.1093/infdis/jiad434.

Reference Type: DERIVED

PMID: 37795976 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

36128

Identifier Type: REGISTRY

Identifier Source: secondary_id

HVTN 120

Identifier Type: -

Identifier Source: org_study_id