| Eligibility |
Inclusion Criteria:
General and demographic criteria:
1. Age of 18 through 55 years
2. Access to a participating HVTN Clinical Research Site (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 (AoU): Volunteer demonstrates understanding of this study
by completing a questionnaire prior to the 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 until
completion of the study
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 risks and amenable to HIV risk-reduction counseling
9. Assessed by the clinic staff as having a low likelihood of acquiring HIV and is
committed to avoiding behaviors associated with a higher likelihood of acquiring HIV
through the last required protocol clinic visit
Laboratory inclusion values Criteria:
10. Hemoglobin (Hgb)
- = 11.0 g/dL for volunteers who were assigned female sex at birth (AFAB)
- = 13.0 g/dL for volunteers who were assigned male sex at birth (AMAB) and
transgender men who have been on hormone therapy for more than 6 consecutive
months
- = 12.0 g/dL for transgender women who have been on hormone therapy for more than
6 consecutive months
- For transgender volunteers who have been on hormone therapy for less than 6
consecutive months, determine Hgb eligibility based on their sex assigned at
birth
11. White blood cell (WBC) count = 2500 to 12000 cells/mm3 with normal differential, or
differential approved by Investigator of Record (IoR) as not clinically significant
12. Total lymphocyte count = 650 cells/mm3 with normal differential, or differential
approved by IoR as not clinically significant
13. Remaining differential either within local lab reference range or with site physician
approval
14. Platelets = 125000 to 550000 cells/mm3
15. Chemistry panel: Alanine aminotransferase (ALT) < 1.25 times the institutional upper
limit of normal (ULN); serum creatinine = 1.1 x ULN based on the local lab reference
range.
16. Corrected total serum calcium level of = 8.5 mg/dL
17. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-approved
enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA)
18. Negative Hepatitis B surface antigen (HBsAg)
19. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV nucleic acid
test (NAT) if the anti-HCV is positive.
Reproductive status criteria:
20. For volunteers AFAB or intersex at birth and are capable of becoming pregnant
(hereafter referred to as "persons of pregnancy potential"):
- Must agree to use effective means of contraception for sexual activity that could
lead to pregnancy from at least 21 days prior to enrollment and 4 weeks after
their last scheduled vaccination timepoint.
- Must have a negative beta human chorionic gonadotropin (ß-HCG) pregnancy test
(urine or serum) at screening (ie, prior to randomization, if applicable) and
prior to study-product administration on the day of study-product administration.
(Persons of pregnancy potential require a pregnancy test prior to injection 1 of
the fractionated escalating dose series)
- Persons who are NOT of pregnancy potential due to having undergone hysterectomy
or bilateral oophorectomy (verified by medical records) or having reached
menopause (no menses for 1 year) are not required to undergo pregnancy testing.
21. AFAB volunteers or volunteers who were intersex at birth must also agree not to seek
pregnancy through alternative methods, such as oocyte retrieval, artificial
insemination or in vitro fertilization until after the last required protocol clinic
visit.
Exclusion Criteria:
General criteria:
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: Age > 45,
systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current
smoker, known hyperlipidemia
4. Intent to participate in any other study that requires non-HVTN HIV Ab testing during
the planned duration of the HVTN 144 study
5. Pregnant or breastfeeding
6. Active duty and reserve US military personnel
Vaccines and other injections criteria:
7. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received
control/placebo in an HIV vaccine trial, the HVTN 144 Protocol Safety Review Team
(PSRT) will determine eligibility on a case-by-case basis.
8. Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational.
Exceptions may be made by the HVTN 144 PSRT on a case-by-case basis.
9. Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine
trial. Exceptions may be made by the HVTN 144 PSRT for vaccines that have subsequently
undergone licensure by the FDA. For volunteers who have received control/placebo in an
experimental vaccine trial, the HVTN 144 PSRT will determine eligibility on a
case-by-case basis. For volunteers who have received an experimental vaccine(s) more
than 1 year ago, eligibility for enrollment will be determined by the HVTN 144 PSRT on
a case-by-case basis.
10. Live attenuated vaccines received within 30 days before the first vaccination or
scheduled within 28 days after injection (eg, measles, mumps, and rubella (MMR); oral
polio vaccine (OPV); varicella; yellow fever; live attenuated influenza vaccine).
ACAM2000 vaccine >28 days prior with a vaccination scab still present.
11. Any vaccines that are not live attenuated vaccines and were received within 14 days
prior to the first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B). Please
note this includes incompetent vaccine such as the Jynneos vaccine for the prevention
of mpox disease.
12. Allergy treatment with antigen injections within 30 days before the first vaccination
or that are scheduled within 14 days after the first vaccination
Immune system criteria:
13. Immunosuppressive medications received within 168 days before first vaccination (not
exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical
corticosteroids for mild, uncomplicated dermatologic condition; or [4] a single course
of oral/parenteral prednisone or equivalent at doses < 60 mg/day and length of therapy
< 11 days with completion at least 30 days prior to enrollment)
14. Serious adverse reactions to vaccines or to vaccine components such as AS01B
("Shingrix") or Matrix M (Novovax CoV2373), including history of anaphylaxis and
related symptoms, such as hives, respiratory difficulty, angioedema, and/or abdominal
pain (not exclusionary: a volunteer who had a nonanaphylactic adverse reaction to
pertussis vaccine as a child).
15. IgG received within 60 days before first vaccination (for mAbs, see criterion #8
above)
16. Autoimmune disease, current or history (not exclusionary: mild, well-controlled
psoriasis)
17. AESIs: Volunteers who currently have, or have a history of, any condition that could
be considered an AESI for the product(s) administered in this protocol.
18. Immunodeficiency
Clinically significant medical conditions criteria:
19. 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.
20. Any medical, 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
21. 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.
22. Current anti-tuberculosis (TB) prophylaxis or therapy
23. Asthma exclusion criteria:
Asthma is excluded if the participant has ANY of the following:
- Required either oral or parenteral corticosteroids for an exacerbation 2 or more
times within the past year; OR
- Needed emergency care, urgent care, hospitalization, or intubation for an acute
asthma exacerbation within the past year (eg, would NOT exclude individuals with
asthma who meet all other criteria but sought urgent/emergent care solely for
asthma medication refills or coexisting conditions unrelated to asthma); OR
- Uses a short-acting rescue inhaler more than 2 days/week for acute asthma
symptoms (ie, not for preventive treatment prior to athletic activity); OR
- Uses medium- to high-dose inhaled corticosteroids (greater than 250 mcg
fluticasone or therapeutic equivalent) or more than 1 medication for maintenance
therapy daily. For example, potential participants taking long-acting
bronchodilator/inhaled corticosteroid combinations for daily maintenance are
excluded (note: maintenance monotherapy with cromolyn, leukotriene receptor
antagonist, or theophylline is not exclusionary).
24. Diabetes mellitus type 1 or type 2 (not exclusionary: type 2 cases controlled with
diet alone or a history of isolated gestational diabetes)
25. Thyroidectomy, or thyroid disease requiring medication during the last 12 months (not
exclusionary: well-controlled non-autoimmune thyroid disease)
26. Hypertension: The average systolic blood pressure between the screening visit and the
enrollment visit must be below 140 mmHg. The average diastolic blood pressure between
the screening visit and the enrollment visit must be below 90 mmHg. A single
measurement greater than or equal to 160 mmHg systolic or 100 mmHg diastolic during
the current study evaluation is exclusionary.
27. Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder requiring
special precautions)
28. Malignancy (not exclusionary: 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)
29. 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.
30. Asplenia: Any condition resulting in the absence of a functional spleen
31. History of angioedema or anaphylaxis (not exclusionary: angioedema or anaphylaxis with
known trigger and no episodes within 5 years)
32. History of generalized urticaria within past 5 years
|
