Clinical Trials

MainTitle

Evaluating the Safety and Immunogenicity of ALVAC-HIV and MF59®- or AS01B-adjuvanted Bivalent Subtype C gp120 in Healthy, HIV-uninfected Adult Participants (HVTN 120)

This study is ongoing, but not recruiting participants.
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator
GlaxoSmithKline
Sanofi Pasteur, a Sanofi Company

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03122223

First received: February 14, 2017
Last updated: October 19, 2018
Last Verified: October 2018
History of Changes
Purpose

Purpose

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

Condition Intervention Phase
HIV Infections

Biological : ALVAC-HIV (vCP2438)
Biological : Bivalent subtype C gp120/MF59
Biological : Bivalent subtype C gp120/AS01(B)
Biological : Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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

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

Primary Outcome Measures

  • Frequency of severe local and systemic reactogenicity signs and symptoms [ Time Frame: 7 days after each vaccine dose ]
  • Frequency of AEs by body system, MedDRA preferred term, severity, and assessed relationship to study products [ Time Frame: 30 days after each vaccine dose ]
  • Frequency of SAEs, AESIs, and new chronic conditions [ Time Frame: 18 months ]
  • Composition of safety laboratory measures: white blood cells, neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, and creatinine at baseline and following vaccinations [ Time Frame: 12 months ]
  • Frequency of AEs leading to early participant withdrawal or early discontinuation of study products administration throughout the study. [ Time Frame: 12 months ]
  • HIV-specific CD4+ T-cell response rates as assessed by flow cytometry [ Time Frame: 12 months ]
  • HIV-specific Env-gp120 response magnitude as assessed by multiplex assay [ Time Frame: 12 months ]
Secondary Outcome Measures:
  • Measure of the HIV-specific total IgG binding antibody response breadth and magnitude as assessed by multiplex assay [ Time Frame: 12 months ]
  • Measure of the Anti-V1/V2 scaffold IgG binding antibody responses as assessed by multiplex assay [ Time Frame: 12 months ]
  • Measure of the HIV-specific CD4+ and CD8+ T-cell responses as assessed by flow cytometry [ Time Frame: 12 months ]
  • Measure of immunogenicity assays may be performed on blood samples based on the HVTN laboratory Assay Algorithm [ Time Frame: 12 months ]

Estimated Enrollment: 160
Study Start Date: January 16, 2018
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: 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.
Biological: 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.

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.

Biological: Placebo

Sodium Chloride for Injection, 0.9%, administered IM.

Active Comparator: 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.
Biological: 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.

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.

Biological: Placebo

Sodium Chloride for Injection, 0.9%, administered IM.

Active Comparator: 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.
Biological: 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.

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.

Biological: Placebo

Sodium Chloride for Injection, 0.9%, administered IM.

Placebo Comparator: 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.
Biological: Placebo

Sodium Chloride for Injection, 0.9%, administered IM.

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.

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:

  • 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 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 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.

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: NCT03122223

Locations

United States, California
Bridge HIV CRS
San Francisco, California, United States, 94143
United States, Georgia
The Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia, United States, 30030
United States, Massachusetts
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, United States, 02115-6110
Fenway Health (FH) CRS
Boston, Massachusetts, United States, 02215-4302
United States, New York
University of Rochester Vaccines to Prevent HIV Infection CRS
Rochester, New York, United States, 14642
United States, Ohio
Case Clinical Research Site
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Penn Prevention CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt Vaccine (VV) CRS
Nashville, Tennessee, United States, 37232-2582
United States, Washington
Seattle Vaccine and Prevention CRS
Seattle, Washington, United States, 98109-1024
Tanzania
National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS
Mbeya, Tanzania
Zambia
Matero Reference Clinic CRS
Lusaka, Zambia, 10101
Zimbabwe
Seke South CRS
Chitungwiza, Zimbabwe

Sponsors and Collaborators

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

Investigators

Study Chair: Z Mike Chirenje UZ-UCSF Collaborative Research Program
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT03122223   History of Changes  
Other Study ID Numbers: HVTN 120  
  36128  
Study First Received: February 14, 2017  
Last Updated: October 19, 2018  
Individual Participant Data    
Plan to Share IPD: No  

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
MF59 oil emulsion

ClinicalTrials.gov processed this data on December 10, 2018
This information is provided by ClinicalTrials.gov.