Evaluating the Safety and Immunogenicity of HIV Clade C DNA Vaccine and MF59- or AS01B-Adjuvanted Clade C Env Protein Vaccines in Various Combinations in Healthy, HIV-Uninfected Adults



Status:Active, not recruiting
Conditions:HIV / AIDS
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:18 - 40
Updated:11/1/2018
Start Date:December 2016

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A Phase 1/2a Clinical Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DNA, and of MF59®- or AS01B-Adjuvanted Clade C Env Protein in Various Combinations, in Healthy, HIV-Uninfected Adult Participants

This study will evaluate the safety and immune response to the DNA-HIV-PT123 vaccine used in
combination with one of two protein vaccines (Bivalent Subtype C gp120/MF59 or Bivalent
Subtype C gp120/AS01B) in healthy, HIV-uninfected adults.

The purpose of this study is to evaluate the safety, tolerability, and immune response of the
DNA-HIV-PT123 vaccine when used in combination with one of two protein vaccines: Bivalent
Subtype C gp120/MF59 (Protein/MF59) or Bivalent Subtype C gp120/AS01B (Protein/AS01B). These
protein vaccines may boost the immune response to the DNA vaccine.

The study will enroll healthy, HIV-uninfected adults. Participants will be randomly assigned
to one of eight groups, and each group will receive a different sequence of vaccines during
the study. Groups 1 and 4 will receive the DNA-HIV-PT123 vaccine, the Protein/MF59 vaccine,
and placebo. Groups 2, 3, 5, 6, and 7 will receive the DNA-HIV-PT123 vaccine, the
Protein/AS01B vaccine, and placebo. Group 8 will only receive placebo.

All participants will receive their assigned vaccines at Months 0, 1, 3, and 6. Each of these
visits will include three injections. Follow-up visits will occur at Week 2 and Months 1.5,
3.5, 6.25, 6.5, 9, and 12.

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 stool, rectal fluid, cervical fluid, or semen samples.
Participants will be contacted 6 months after the last scheduled visit by phone, text
message, or e-mail for information about their health.

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;
completes 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 protocol clinic visit

- Willing to be contacted by phone, text message, or e-mail 6 months after completion of
the scheduled clinic visits

- Good general health as shown by medical history, physical exam, and screening
laboratory tests

HIV-Related Criteria:

- Willingness to receive HIV test results

- Willingness to discuss HIV infection risks and amenable to HIV risk reduction
counseling.

- Assessed by the clinic staff as being at "low risk" for HIV infection and committed to
maintaining behavior consistent with low risk of HIV exposure through the last
required protocol clinic visit.

Laboratory Inclusion Values:

Hemogram/Complete Blood Count (CBC)

- Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female,
greater than or equal to 13.0 g/dL for volunteers who were born male

- White blood cell count equal to 3,300 to 12,000 cells/mm^3

- Total lymphocyte count greater than or equal to 800 cells/mm^3

- Remaining differential either within institutional normal range or with site physician
approval

- Platelets equal to 125,000 to 550,000/mm^3

Chemistry

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

Virology

- Negative HIV-1 and -2 blood test: US volunteers must have a negative 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 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:

United States

A volunteer who was born female must:

- Agree to consistently use effective contraception (see the protocol for more
information) for sexual activity that could lead to pregnancy from at least 21 days
prior to enrollment 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:

- Condoms (male or female) with or without a spermicide,

- Diaphragm or cervical cap with spermicide,

- Intrauterine device (IUD),

- Hormonal contraception, or

- 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 108 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.

Southern Africa

A volunteer who was born female must:

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

- Condoms (male or female)

- Diaphragm or cervical cap

- PLUS 1 of the following methods:

- IUD,

- Hormonal contraception (in accordance with applicable national contraception
guidelines), or

- 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 108 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.

- 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 21 years of age and older 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
atypical squamous cells of undetermined significance (ASCUS), or

- the 5 years prior to enrollment, with the latest result reported as normal, or
ASCUS with no evidence of high risk human papillomavirus (HPV).

- If no pap smear was done within the last 3 years (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 108 study

- Pregnant or breastfeeding

- Active duty and reserve US military personnel

Vaccines and Other Injections

- HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received
control/placebo in an HIV vaccine trial, the HVTN 108 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 108 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 108 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 less than 2 mg/kg/day and length of therapy
less than 11 days with completion at least 30 days prior to enrollment.)

- Serious adverse reactions to vaccines or to vaccine components including history of
anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema,
and/or abdominal pain. (Not excluded from participation: a volunteer who had a
nonanaphylactic adverse reaction to pertussis vaccine as a child.)

- Immunoglobulin received within 60 days before first vaccination

- Autoimmune disease

- 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 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, including cases controlled with diet alone. (Not
excluded: history of isolated gestational diabetes.)

- Thyroidectomy, or thyroid disease requiring medication during the last 12 months

- Hypertension:

- If a person has been found to have elevated blood pressure or hypertension during
screening or previously, exclude for blood pressure that is not well controlled.
Well-controlled blood pressure is defined as consistently less than or equal to
140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without
medication, with only isolated, brief instances of higher readings, which must be
less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg
diastolic. For these volunteers, blood pressure must be less than or equal to 140
mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment.

- If a person has NOT been found to have elevated blood pressure or hypertension
during screening or previously, exclude for systolic blood pressure greater than
or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or
equal to 100 mm Hg at enrollment.

- Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or
platelet disorder requiring special precautions)

- Malignancy (Not excluded from participation: Volunteer who has had malignancy excised
surgically and who, in the investigator's estimation, has a reasonable assurance of
sustained cure, or who is unlikely to experience recurrence of malignancy during the
period of the study)

- Seizure disorder: History of seizure(s) within past 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.
We found this trial at
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New York, New York 10032
Phone: 212-342-2958
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Birmingham, Alabama 35294
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Boston, Massachusetts 02115
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Boston, Massachusetts 02215
Phone: 617-927-6021
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Johannesburg, Gauteng
Phone: 27-844072729
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Nashville, Tennessee 37232
Phone: 615-322-5641
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New York, New York 10065
Phone: 212-388-0008
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Rochester, New York 14642
Phone: 585-275-5871
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Seattle, Washington 98109
Phone: 206-667-2344
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