| Eligibility |
Inclusion Criteria:
1. Age of 18 through 50 years
2. Access to a participating 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
and completes a questionnaire prior to first study-product administration 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 last required protocol clinic visit.
6. Good general health as shown by medical history, physical exam, and screening
laboratory tests
7. Willingness to receive HIV test results
8. Willingness to discuss HIV acquisition and amenable to HIV risk-reduction counseling.
9. Assessed by the clinic staff as having a low likelihood of HIV acquisition and is
committed to avoid behaviors associated with a higher likelihood of acquiring HIV
through the last required protocol clinic visit.
10. Hemoglobin
- = 11.0 g/dL for AFAB volunteers
- = 13.0 g/dL for AMAB volunteers 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 hemoglobin eligibility based on their sex assigned
at birth
11. White blood cell (WBC) count = 2,500 to 12,000 cells/mm3
12. WBC differential either within institutional normal range or with site clinician
approval
13. Platelets = 125,000 to 550,000 cells/mm3
14. Chemistry panel: alanine aminotransferase (ALT) < 1.25 times the institutional upper
limit of normal (ULN) (ie, < 1.25 times the reference range upper limit) and
creatinine < 1.1 times the institutional ULN (ie, < 1.1 times the reference range
upper limit)
15. Negative HIV-1 and -2 blood test: Sites may use locally available assays that have
been approved by HVTN and HPTN Laboratory Operations
16. Negative Hepatitis B surface antigen (HBsAg)
17. Negative anti-Hepatitis C virus Abs (anti-HCV) or negative HCV PCR if the anti-HCV is
positive
18. Negative or trace urine protein
19. AFAB volunteers or volunteers who were intersex at birth and are capable of becoming
pregnant (hereafter referred to as "persons of pregnancy potential"): negative serum
or urine beta human chorionic gonadotropin (ß-HCG) pregnancy test(s) performed within
48 hours prior to initial study-product administration. Persons who are NOT of
pregnancy potential due to having undergone total hysterectomy or bilateral
oophorectomy (verified by medical records) are not required to undergo pregnancy
testing.
20. Persons of pregnancy potential must:
- Agree to use effective contraception for sexual activity that could lead to
pregnancy from at least 21 days prior to enrollment through the last required
protocol visit. Effective contraception is defined as using one of the following
methods:
- Condoms (internal and external) with or without a spermicide,
- Diaphragm or cervical cap with spermicide,
- Intrauterine device (IUD),
- Hormonal contraception,
- Tubal ligation, or
- Any other contraceptive method approved by the HVTN 143/HPTN 109 PSRT
- Successful vasectomy in any AMAB partner (considered successful if a
volunteer reports that an AMAB 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,
- Not be of pregnancy potential, such as having reached menopause (no menses for 1
year) or having undergone hysterectomy or bilateral oophorectomy; or,
- Be sexually abstinent.
21. AFAB volunteers or 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 from at least 21 days prior to enrollment through 8 weeks until
after the last required protocol clinic visit
Exclusion Criteria:
1. Weight < 35 kg or > 115 kg
2. Blood products received within 120 days before first study-product administration,
unless eligibility for earlier enrollment is determined by the HVTN 143/HPTN 109 PSRT
3. Investigational research agents received within 30 days before first study-product
administration
4. Intent to participate in another study of an investigational research agent or any
other study that requires non-Network HIV Ab testing during the planned duration of
the HVTN 143/HPTN 109 study
5. Pregnant or breastfeeding
6. HIV vaccine(s) received in a prior HIV vaccine trial. Volunteers who have received
control/placebo in an HIV vaccine trial are not excluded from HVTN 143/HPTN 109.
7. SARS-CoV-2 vaccine(s) received within 7 days prior to HVTN 143/HPTN 109 enrollment or
planned within 7 days after enrollment.
8. Jynneos vaccine for MPOX received within 14 days prior to enrollment or planned within
14 days after enrollment.
9. ACAM2000 vaccine for MPOX received within 28 days prior to enrollment or, if ACAM2000
was received more than 28 days prior to enrollment, vaccination scab still present; or
planned within 14 days after enrollment
10. Receipt of humanized or human mAbs, whether licensed or investigational.
11. Previous receipt of mAbs targeting HIV (eg, cap256, VRC01, VRC01LS, VRC07-523LS,
PGDM1400, PGDM1400LS, PGT121, PGT121.414.LS)
12. Immunosuppressive medications received within 30 days before first study-product
administration (not exclusionary: [1] corticosteroid nasal spray; [2] inhaled
corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatological
condition; or [4] a single course of oral/parenteral prednisone or equivalent at doses
< 20 mg/day and length of therapy < 14 days, but completed at least 7 days prior to
first infusion)
13. Serious adverse reactions to VRC01.23LS, PGDM1400LS, or PGT121.414.LS formulation
components, including history of anaphylaxis and related symptoms such as hives,
respiratory difficulty, angioedema, and/or abdominal pain.
14. Immunoglobulin received within 60 days before first study-product administration (for
mAb, see criterion 10 above)
15. Autoimmune disease (not exclusionary: volunteer with mild, stable, and uncomplicated
autoimmune disease that does not require immunosuppressive medication and that, in the
judgment of the CRS investigator, is likely not subject to exacerbation and likely not
to complicate solicited and unsolicited AE assessments)
16. Immunodeficiency
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:
- Symptoms consistent with COVID-19 or known SARS-CoV-2 acquisition,
- A process that would affect the immune response,
- A process that would require medication that affects the immune response,
- Any contraindication to repeated infusions or blood draws, including inability to
establish venous access,
- 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 (eg, chronic urticaria or recent injection or infusion
with evidence of residual inflammation) for which signs or symptoms could be
confused with reactions to the study product, or
- Any condition specifically listed among the exclusion criteria.
18. Any medical, psychiatric, or skin condition (eg, tattoos) or occupational
responsibility that, in the judgment of the investigator, would interfere with or
serve as a contraindication to protocol adherence, assessment of safety or solicited
AEs, or a participant's ability to give informed consent.
19. Psychiatric condition that precludes compliance with the protocol. Specifically
excluded are persons with psychoses, ongoing risk for suicide, or history of suicide
attempt within the past 3 years.
20. Current anti-tuberculosis (TB) 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 had either of the following:
- Greater than 1 exacerbation of symptoms treated with oral/parenteral
corticosteroids;
- Emergency care, urgent care, hospitalization, or intubation for asthma.
22. Diabetes mellitus type 1 or type 2 (not exclusionary: type-2 cases controlled with
diet alone or a history of isolated gestational diabetes)
23. 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 in this protocol 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.
24. Bleeding disorder diagnosed by a clinician (eg, factor deficiency, coagulopathy, or
platelet disorder requiring special precautions)
25. Malignancy (not exclusoinary: 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)
26. 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.
27. Asplenia: any condition resulting in the absence of a functional spleen
28. History of generalized urticaria, angioedema, or anaphylaxis (not exclusionary:
angioedema or anaphylaxis to a known trigger with at least 5 years since last reaction
to demonstrate satisfactory avoidance of trigger)
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