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Clinical Trials

MainTitle

Safety and Immunogenicity of Clade C ALVAC and gp120 HIV Vaccine (HVTN107)

This study is currently recruiting participants. (see Contacts and Locations)

Verified September 2017 by National Institute of Allergy and Infectious Diseases (NIAID)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator
HIV Vaccine Trials Network
Sanofi Pasteur, a Sanofi Company
GlaxoSmithKline

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03284710

First received: September 13, 2017
Last updated: September 13, 2017
Last Verified: September 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections

Biological : ALVAC-HIV (vCP2438)
Biological : Bivalent Subtype C gp120/MF59
Biological : Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension
Biological : Bivalent Subtype C gp120
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 1/2a Partially Double-blinded, Randomized Clinical Trial to Characterize the Safety and Immunogenicity of Clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120 Alone, With MF59 Adjuvant, and With Alum Adjuvant in Healthy, HIV-uninfected Adult Participants

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Occurrence and level of vaccine-induced systemic IgG Ab binding to the 3 gp120 Env proteins contained in the vaccine regimen (ZM96, TV1.C, and 1086.C) [ Time Frame: Measured at Month 6.5 ]
  • Occurrence and level of vaccine-induced serum IgA Ab binding to the 3 gp120 Env proteins contained in the vaccine regimen (ZM96, TV1.C, and 1086.C) [ Time Frame: Measured at Month 6.5 ]
  • Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia) [ Time Frame: Measured through Month 12 ]
  • Frequency of adverse events (AEs) [ Time Frame: Measured through Month 15 ]
    By body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products
Secondary Outcome Measures:
  • Vaccine-induced serum IgG Ab binding to V2 Env proteins [ Time Frame: Measured through 18 months ]
  • Vaccine-induced CD4+ T-cell responses to the HIV proteins [ Time Frame: Measured through 18 months ]
  • Vaccine-induced serum IgG3 Ab binding to Env proteins [ Time Frame: Measured through 18 months ]
  • HIV-specific CD4+ T cell polyfunctionality by ICS [ Time Frame: Measured through 18 months ]
  • Occurrence and level of vaccine-induced systemic IgG Ab binding to the 3 gp120 Env proteins contained in the vaccine regimen (ZM96, TV1.C, and 1086.C) [ Time Frame: Measured through 18 months ]

Estimated Enrollment: 132
Study Start Date: June 19, 2017
Estimated Study Completion Date: September 30, 2019
Estimated Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: 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.
Biological: 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

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

Active Comparator: 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.
Biological: 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

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

Active Comparator: 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.
Biological: 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

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

Active Comparator: 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.
Biological: 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

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

Detailed Description:

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 40 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: Yes  

Criteria

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:
  • 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 ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male
  • White blood cell count = 3,300 to 12,000 cells/mm^3
  • Total lymphocyte count ≥ 800 cells/mm^3
  • Remaining differential either within institutional normal range or with site physician approval
  • Platelets = 125,000 to 550,000/mm^3

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

  • Virology
  • Negative HIV-1 and -2 blood test: 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 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 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.
  • 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
  • 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
  • Blood products received within 120 days before first vaccination
  • Investigational research agents received within 30 days before first vaccination
  • 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
  • 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
  • Pregnant or breastfeeding

  • 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 107 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 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.
  • 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)
  • 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)
  • 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 corticosteroids at doses < 2 mg/kg/day and length of therapy < 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 vaccination
  • Autoimmune disease
  • 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 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 ≤ 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.
  • 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.

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT03284710

    Contacts

    Contact:   Marianne Hansen 206-667-6658 mhansen@fredhutch.org
    Contact:   Michelle Nebergall +27 (0)79 510 5540 mneberga@fredhutch.org

    Locations

    Mozambique
    Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS Recruiting
    Maputo, Mozambique
    Contact: Ilesh V Jani    258-84-3012208    ilesh.jani@gmail.com
    Contact: Nilesh B Bhatt    258-82-3861130    nbhatt.mz@gmail.com
    South Africa
    Aurum Tembisa CRS Recruiting
    Johannesburg, Gauteng, South Africa, 1632
    Contact: Modulakgotla A Sebe    27-87-1351645    msebe@auruminstitute.org
    Contact: Gladys Kobane    27-87-1351533    gkobane@auruminstitute.org
    Soweto HVTN CRS Recruiting
    Johannesburg, Gauteng, South Africa, 1862
    Contact: Fatima Laher    27-11-9899700    laherf@phru.co.za
    Contact: Mmathapelo Masala    27-11-9899819    masalam@phru.co.za
    eThekwini CRS Recruiting
    Durban, Kwa Zulu Natal, South Africa, 4013
    Contact: Nesri Padayatchi    27-31-2604550    Nesri.padayatchi@caprisa.org
    Contact: Kalendri Naidoo    27-31-2601956    Kalendri.naidoo@caprisa.org
    Emavundleni CRS Recruiting
    Cape Town, Western Cape, South Africa, 7750
    Contact: Gonasagrie Nair, MD    27-21-6505848    Lulu.Nair@hiv-research.org.za
    Contact: Goodness Mvuyane, BS    27-21-6505889    Goodness.Mvuyane@hiv-research.org.za
    Zimbabwe
    Seke South CRS Recruiting
    Chitungwiza, Mashonaland East, Zimbabwe
    Contact: Portia Hunidzarira    263-777-817265    phunidzarira@uzchs-ctu.org
    Contact: Margaret Mlingo    263-772-285034    mmlingo@uzchs-ctu.org

    Sponsors and Collaborators

    National Institute of Allergy and Infectious Diseases (NIAID)
    HIV Vaccine Trials Network
    Sanofi Pasteur, a Sanofi Company
    GlaxoSmithKline

    Investigators

    Study Chair: Paul Goepfert University of Alabama at Birmingham
    Study Chair: Kathy Mngadi Centre for the AIDS Programme of Research in South Africa
    More Information

    More Information


    Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
    ClinicalTrials.gov Identifier: NCT03284710   History of Changes  
    Other Study ID Numbers: HVTN 107  
    Study First Received: September 13, 2017  
    Last Updated: September 13, 2017  

    Studies a U.S. FDA-regulated Drug Product: Yes  
    Studies a U.S. FDA-regulated Device Product: No  
    Product Manufactured in and Exported from the U.S.: Yes  

    Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

    HIV

    Additional relevant MeSH terms:
    HIV Infections
    Vaccines
    MF59 oil emulsion
    Aluminum Hydroxide

    ClinicalTrials.gov processed this data on October 17, 2017
    This information is provided by ClinicalTrials.gov.