Safety and Immunogenicity of Clade C ALVAC and gp120 HIV Vaccine

NCT ID: NCT03284710

Last Updated: 2024-09-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

132 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-19

Study Completion Date

2019-12-12

Brief Summary

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The purpose of this study is to evaluate the safety and immune response to an HIV clade C vaccine and to an MF59- or alum-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.

Detailed Description

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This study will evaluate the safety, tolerability, and immunogenicity to vCP2438 (an HIV clade C vaccine) and to an unadjuvanted or MF59- or alum-adjuvanted bivalent clade C gp120 in healthy, HIV-uninfected adults.

The study will enroll healthy, HIV-uninfected participants aged 18 to 40 years. Participants will be randomly assigned to one of 4 groups. \[describe further\]

Study visits will include a physical examination, an interview and/or questionnaire, HIV testing and HIV risk-reduction counseling, and urine and blood collection. A subset of participants will provide rectal fluid, cervical fluid, semen, or stool samples.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Group 1: ALVAC-HIV + gp120/MF59

Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120/MF59 in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.

Group Type ACTIVE_COMPARATOR

ALVAC-HIV (vCP2438)

Intervention Type BIOLOGICAL

Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10\^6 cell culture infectious dose (CCID)50 and \< 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose

Bivalent Subtype C gp120/MF59

Intervention Type BIOLOGICAL

Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant (an oil-in-water emulsion); delivered as a 0.5 mL IM injection

Group 2: ALVAC-HIV + gp120/Al(OH)3

Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.

Group Type ACTIVE_COMPARATOR

ALVAC-HIV (vCP2438)

Intervention Type BIOLOGICAL

Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10\^6 cell culture infectious dose (CCID)50 and \< 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose

Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension

Intervention Type BIOLOGICAL

Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, admixed with Aluminum Hydroxide Suspension (\~625 mcg aluminum content); delivered as a 0.5 mL IM injection

Group 3: ALVAC-HIV + gp120/MF59

Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid and Bivalent Subtype C gp120/MF59 in the right deltoid at months 0, 1, 6, and 12. All injections are via needle and syringe.

Group Type ACTIVE_COMPARATOR

ALVAC-HIV (vCP2438)

Intervention Type BIOLOGICAL

Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10\^6 cell culture infectious dose (CCID)50 and \< 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose

Bivalent Subtype C gp120/MF59

Intervention Type BIOLOGICAL

Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant (an oil-in-water emulsion); delivered as a 0.5 mL IM injection

Group 4: ALVAC-HIV + gp120

Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120 in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.

Group Type ACTIVE_COMPARATOR

ALVAC-HIV (vCP2438)

Intervention Type BIOLOGICAL

Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10\^6 cell culture infectious dose (CCID)50 and \< 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose

Bivalent Subtype C gp120

Intervention Type BIOLOGICAL

Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, mixed with sodium chloride for injection, 0.9%; delivered as a 0.5 mL IM injection

Interventions

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ALVAC-HIV (vCP2438)

Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10\^6 cell culture infectious dose (CCID)50 and \< 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose

Intervention Type BIOLOGICAL

Bivalent Subtype C gp120/MF59

Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant (an oil-in-water emulsion); delivered as a 0.5 mL IM injection

Intervention Type BIOLOGICAL

Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension

Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, admixed with Aluminum Hydroxide Suspension (\~625 mcg aluminum content); delivered as a 0.5 mL IM injection

Intervention Type BIOLOGICAL

Bivalent Subtype C gp120

Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, mixed with sodium chloride for injection, 0.9%; delivered as a 0.5 mL IM injection

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

General and Demographic Criteria

1. Age of 18 to 40 years
2. Access to a participating HVTN CRS and willingness to be followed for the planned duration of the study
3. Ability and willingness to provide informed consent
4. 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
5. Agrees not to enroll in another study of an investigational research agent
6. Good general health as shown by medical history, physical exam, and screening laboratory tests

HIV-Related Criteria:
7. Willingness to receive HIV test results
8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
9. 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)
10. Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male
11. White blood cell count = 3,300 to 12,000 cells/mm\^3
12. Total lymphocyte count ≥ 800 cells/mm\^3
13. Remaining differential either within institutional normal range or with site physician approval
14. Platelets = 125,000 to 550,000/mm\^3

Chemistry
15. Chemistry panel: ALT, AST, and ALP \< 1.25 times the institutional upper limit of normal; creatinine ≤ institutional upper limit of normal.

Virology
16. Negative HIV-1 and -2 blood test: Sites may use locally available assays that have been approved by HVTN Laboratory Operations.
17. Negative Hepatitis B surface antigen (HBsAg)
18. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive Urine
19. 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
20. 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.
21. Reproductive status: A volunteer who was born female must:

* Agree to consistently use effective contraception 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 is defined as using condoms (male or female), or diaphragm or cervical cap, PLUS 1 of the following methods: Intrauterine device (IUD), Hormonal contraception (in accordance with Republic of South Africa: National Contraception Clinical Guidelines), 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 any other contraceptive method approved by the HVTN 107 Protocol Safety Review Team
* 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.
22. 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

Other
23. Volunteers who were born female 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); for those 21 years and older that have not had a pap smear within the last 3 years prior to enrollment, must be willing to undergo a pap smear with the result reported as normal or ASCUS prior to sample collection.

Exclusion Criteria

General

1. Blood products received within 120 days before first vaccination
2. Investigational research agents received within 30 days before first vaccination
3. Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg, current smoker, known hyperlipidemia
4. 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 107 study
5. Pregnant or breastfeeding

Vaccines and other Injections
6. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 107 PSRT will determine eligibility on a case-by-case basis.
7. 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 in a volunteer's country of residence. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 107 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 107 PSRT on a case-by-case basis.
8. Live attenuated vaccines other than influenza vaccine 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)
9. Influenza vaccine or 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)
10. Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination

Immune System
11. 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 corticosteroids at doses \< 2 mg/kg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment.)
12. 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.)
13. Immunoglobulin received within 60 days before first vaccination
14. Autoimmune disease
15. Immunodeficiency

Clinically significant medical conditions
16. Untreated or incompletely treated syphilis infection
17. 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
18. 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
19. 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.
20. Current anti-tuberculosis (TB) prophylaxis or therapy
21. 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.
22. Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
23. Thyroidectomy, or thyroid disease requiring medication during the last 12 months
24. 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 ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and ≤ 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 ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.
25. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
26. 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)
27. 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.
28. Asplenia: any condition resulting in the absence of a functional spleen
29. 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

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HIV Vaccine Trials Network

NETWORK

Sponsor Role collaborator

Sanofi Pasteur, a Sanofi Company

INDUSTRY

Sponsor Role collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Goepfert

Role: STUDY_CHAIR

University of Alabama at Birmingham

Kathy Mngadi

Role: STUDY_CHAIR

Centre for the AIDS Programme of Research in South Africa

Locations

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Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS

Maputo, , Mozambique

Site Status

Aurum Tembisa CRS

Johannesburg, Gauteng, South Africa

Site Status

Soweto HVTN CRS

Johannesburg, Gauteng, South Africa

Site Status

eThekwini CRS

Durban, KwaZulu-Natal, South Africa

Site Status

Emavundleni CRS

Cape Town, Western Cape, South Africa

Site Status

Seke South CRS

Chitungwiza, Mashonaland East Province, Zimbabwe

Site Status

Countries

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Mozambique South Africa Zimbabwe

References

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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)

Moodie Z, Andersen-Nissen E, Grunenberg N, Dintwe OB, Omar FL, Kee JJ, Bekker LG, Laher F, Naicker N, Jani I, Mgodi NM, Hunidzarira P, Sebe M, Miner MD, Polakowski L, Ramirez S, Nebergall M, Takuva S, Sikhosana L, Heptinstall J, Seaton KE, De Rosa S, Diazgranados CA, Koutsoukos M, Van Der Meeren O, Barnett SW, Kanesa-Thasan N, Kublin JG, Tomaras GD, McElrath MJ, Corey L, Mngadi K, Goepfert P; HVTN 107 Protocol Team. Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial. PLoS Med. 2024 Mar 19;21(3):e1004360. doi: 10.1371/journal.pmed.1004360. eCollection 2024 Mar.

Reference Type DERIVED
PMID: 38502656 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HVTN 107

Identifier Type: -

Identifier Source: org_study_id

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