Inclusion Criteria:
1. Each potential study participant must pass the Test of Understanding (TOU), indicating
that he or she understands the purpose of, and procedures required for the study,
after reading the informed consent and after the investigator or designee has provided
detailed information on the study and has answered the potential study participant's
questions. Each study participant must subsequently sign the ICF, indicating that he
or she is willing to participate in the study.
2. Each study participant must be willing and able to adhere to the prohibitions and
restrictions specified in this protocol.
3. Study participants are ≥18 to ≤70 years old on the day of signing the ICF.
4. Each study participant must have documented HIV-1 infection.
5. Must be on suppressive ART for at least 48 weeks prior to screening. ART is defined as
a combination therapy regimen including at least 2 compounds, e.g., integrase
inhibitor and nucleoside reverse transcriptase inhibitors (such as DovatoTM) or more
than 2 compounds, e.g., 2x nucleoside reverse transcriptase inhibitors plus integrase
inhibitor.
6. Must have a plasma HIV RNA <50 cps/mL at screening and at least 1 documented evidence
of plasma HIV RNA <50 cps/mL after the last ART change.
7. Must be willing to undergo ATI.
8. Must be medically stable as confirmed by medical history, physical examination, vital
signs, and clinical laboratory tests performed at screening, and as per the
investigator's discretion.
9. Ability and willingness to restart ART according to study guidelines.
10. Each study participant must meet the following laboratory criteria prior to
randomization:
- - Hemoglobin: Women ≥10.5 g/dL; Men ≥11.0 g/dL.
- - White cell count: 2,500 to 11,000 cells/mm3, inclusive.
- - Absolute neutrophil count: >1,000 cells/mm3.
- - Platelets: 125,000 to 450,000 per mm3, inclusive.
- - Screening serum liver enzymes (e.g., alanine aminotransferase [ALT], aspartate
aminotransferase [AST], total bilirubin): within the normal reference ranges at
baseline.
- - Creatinine: <1.2 x ULN.
- - Estimated glomerular filtration rate ≥ 60 mL/min.
- - CD4+: >450 cells/mm3 at screening and at least 1 documented result >300 cells/mm3
during 48 weeks before randomization (for nadir, see exclusion criterion 9)
- Troponin: <1 x ULN.
11. For participants who are able to become pregnant, negative serum or urine pregnancy
test (with a sensitivity of 15-25 mIU/mL) within 24 hours prior to Stage 1
randomization. 12. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction starting from the first vaccination at Week 0 visit and for a period of
24 weeks after last dose of bNAb.
Exclusion Criteria:
1. Anyone who is pregnant, breastfeeding, or planning to become pregnant while enrolled
in this study.
2. Anyone with contraindication to intramuscular injections, placement of intravenous
lines, and blood draws eg, bleeding disorders. NOTE: nonsteroidal anti- inflammatory
drugs (NSAIDS) and acetylsalicylic acid containing preparations have to be stopped for
5 days before and after planned leukapheresis.
3. Anyone with acute illness (this does not include minor illnesses such as diarrhea or
mild upper respiratory tract infection) or temperature ≥38.0oC within 24 hours prior
to the first dose of study vaccine; enrollment at a later date is permitted.
4. Any history of an HIV-associated malignancy (including Kaposi's sarcoma), and any type
of lymphoma, or virus-associated cancers.
5. Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or
surgery in the 36 months prior to Stage 1 randomization or for whom such therapies are
expected in the next 12 months (exceptions are squamous and basal cell carcinomas of
the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured
with minimal risk of recurrence).
6. Anyone with a history of an underlying clinically significant acute or uncontrolled
chronic medical condition or physical examination findings for which, in the opinion
of the investigator, participation would not be in the best interest of the study
participant.
7. History or current clinical atherosclerotic cardiovascular disease, as defined by 2013
American College of Cardiology (ACC)/American Heart Association (AHA) guidelines,
including a previous diagnosis of any of the following:
- - Acute myocardial infarction.
- - Acute coronary syndromes.
- - Stable or unstable angina.
- - Coronary or other arterial revascularization.
- - Peripheral arterial disease presumed to be of atherosclerotic origin.
8. Anyone with a history of HIV-related illness under CDC Category C (except for
recurrent pneumonia) within 10 years prior to screening, based on available medical
history and assessed by the investigator for clinical relevance.
9. Anyone with a history of repeated CD4+ <200 cells/mm3, based on available medical
history and assessed by the investigator for clinical relevance. .
10. Current receipt of ART other than nucleoside reverse transcriptase inhibitor and
integrase inhibitor.
11. Anyone who had major surgery (per the investigator's judgment), within 12 weeks before
dosing, or has not have fully recovered from surgery, or has surgery planned during
the time the study participant is expected to participate in the study or within 6
months after the last dose of study vaccine administration.
12. Anyone with a history of myocarditis, pericarditis, cardiomyopathy, congestive heart
failure with permanent sequelae, clinically significant arrhythmia (including any
arrhythmia requiring medication, treatment, or clinical follow-up).
13. Anyone with an ECG with reading and showing clinically significant findings, or
features that would interfere with the assessment of myocarditis/pericarditis.
14. Current advanced liver disease (non-alcoholic fatty liver disease, steatohepatitis, or
alcoholic liver disease) with known or suspected cirrhosis or fibrosis score ≥F2.
15. Anyone with chronic active hepatitis B (measured by hepatitis B surface antigen test)
or active hepatitis C (measured by hepatitis C virus [HCV] antibody test; if positive,
HCV RNA polymerase chain reaction test will be used to confirm active versus past HCV
infection) or syphilis infection that has not been effectively treated. Positive
syphilis serology due to past effectively treated infection is not exclusionary.
16. Anyone with active, untreated gonorrhea or chlamydia infection will be referred to a
clinician for appropriate treatment. If chlamydia and/or gonorrhea treatment is
successfully completed, the participant is eligible for a repeat gonorrhea or
chlamydia screening test and potential study entry.
17. Anyone with thyroidectomy or active thyroid disease requiring medication during the
last 12 months (Not excluded: a stable thyroid supplementation).
18. Anyone with history of HIV-associated neurocognitive disease or progressive multifocal
leukoencephalopathy.
19. Anyone who has had major psychiatric illness and/or drug or alcohol abuse which in the
investigator's opinion would compromise the study participant's safety and/or
compliance with the study procedures.
20. Anyone with a history of thrombosis with thrombocytopenia syndrome (TTS), or
Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS)
21. Anyone who received treatment with immunoglobulins in the 2 months or blood products
in the 4 months before the planned administration of the first dose of study vaccine
or has any plans to receive such treatment during the study. Prior recipients of
anti-HIV bNAbs, independently of the timing, are excluded.
22. Anyone who received or plans to receive:
1. licensed live attenuated vaccines
- - within 28 days before or after planned
administration of any of the study products.
2. other licensed (not live) vaccines
- - within 14 days before or after planned
administration of any of the study products.
3. SARS-CoV-2 vaccines under Emergency Use Authorization (EUA) by the FDA
- - within
28 days before or after planned administration of any of the study products.
23. Anyone who received an investigational drug (not under EUA by the FDA) or used an
invasive investigational medical device within 30 days or received an investigational
vaccine within 6 months before the planned administration of the first dose of study
vaccine. Receipt of prophylactic or therapeutic HIV vaccine candidate at any time is
always exclusionary.
24. Anyone who is currently enrolled or plans to participate in another investigational
study during the course of this study.
25. Anyone who has known allergy or history of anaphylaxis or other serious adverse
reactions to vaccines or vaccine products (including any of the constituents of the
study vaccines) and specifically to neomycin or streptomycin or egg products.
26. Anyone with a history of chronic urticaria (recurrent hives) or a history of chronic
or recurrent eczema and/or atopic dermatitis.
27. Anyone with abnormal function of the immune system resulting from:
1. Clinical conditions (e.g., autoimmune disease or immunodeficiency that are not
HIV related).
2. Chronic or recurrent use of systemic corticosteroids.
3. Administration of antineoplastic and immunomodulating agents or radiotherapy.
28. Anyone with history of acute polyneuropathy(e.g.,Guillain-Barré syndrome).
29. Anyone who cannot communicate reliably with the investigator.
30. Known resistance to 1 or more drugs in 2 or more ARV drug classes.
31. Weight >115kg.
32. Anyone who, in the opinion of the investigator, is unlikely to adhere to the
requirements of the study, or is unlikely to complete the full course of vaccination
and observation.
33. Any employee of the investigator or study site, with direct involvement in the
proposed study or other studies under the direction of that investigator or study
site, as well as family members of the employees or the investigator, or an employee
of the sponsor (or its partners).
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