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Protocol Details

A Randomized Placebo-controlled Study to Evaluate the Safety and Effects of Repeated Doses of 3BNC117-LS and 10-1074-LS on Persistent Viral Reservoirs in People Living with HIV and on Suppressive Antiretroviral Therapy

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001037-I

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 70

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

bNAb;
HIV Reservoir

Recruitment Keyword(s)

None

Condition(s)

HIV-1

Investigational Drug(s)

10-1074-LS
3BNC117-LS

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: 3BNC117-LS
Biological/Vaccine: 10-1074-LS
Other: Sterile Saline

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

Antiretroviral therapy (ART) can suppress HIV to undetectable levels in people, but the virus rebounds quickly if the drug treatment is stopped; this is because HIV can remain dormant in a pool of blood cells called the persistent viral reservoir (PVR). Yet lifelong ART is expensive and can lead to serious side effects over the long term. Some drugs may be more effective at reducing the PVR.

Objective:

To see if 2 study drugs (3BNC117-LS and 10-1074-LS) are safe and if they can lower the number of HIV-infected blood cells in people with HIV who are on ART.

Eligibility:

People aged 18 to 70 years with HIV who are on ART.

Design:

Participants will be screened. They will have a physical exam and blood and urine tests. They will undergo leukapheresis. Leukapheresis is a procedure where blood is drawn from a needle in one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be given back through a second needle in the other arm.

The study drugs or placebo (normal saline) will be administered 3 times at 20-week intervals. The drugs will be given through a tube attached to a needle inserted into a vein in the arm. This will take 1 hour. Some participants will receive only a saline solution. They will not know if they are getting the drugs or the placebo.

Participants will undergo leukapheresis up to 4 more times during the study.

Participants will have follow-up visits every 10 weeks until the study ends.

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Eligibility

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Ability to provide informed consent;

2. Stated willingness to comply with all study procedures and availability for the duration of the study;

3. Adult persons of any sex or gender, aged 18 years to 70;

4. Confirmed HIV-1 infection and clinically stable;

5. On antiretroviral therapy with plasma HIV-1 RNA levels of < 50 copies/mL and no reported interruption of ART for 7 consecutive days or longer for at least 96 weeks. NOTE: At least two viral load (VL) measurements within 48 weeks prior to the screening visit must be available for review. A single plasma HIV-1 RNA > 50 copies/mL but < 200 copies/mL over 48 weeks that is followed by an HIV-1 RNA < 50 copies/mL is permitted;

6. Current CD4+ T cell counts > 300 cells/mcL;

7. For participants who can become pregnant (i.e., participants who have not been postmenopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, or who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy), must have a negative pregnancy test at screening and within 48 hours prior to day 0; NOTE: Participant-reported history is acceptable as documentation of hysterectomy and bilateral oophorectomy, tubal ligation, tubal micro-inserts, and vasectomy.

8. Participants who can become pregnant must agree to use adequate measures to prevent pregnancy. This includes the use an effective method of contraception for the study duration. Contraception must be used from 10 days prior to the first dose of the investigational products (IPs), while receiving the IPs and during study follow up. Acceptable methods of contraception include:

- Contraceptive subdermal implant

- Intrauterine device or intrauterine system

- Combined estrogen and progestogen oral contraceptive

- Injectable progestogen

- Contraceptive vaginal ring

- Percutaneous contraceptive patches

NOTE: Partner sterilization with documentation of azoospermia prior to the participant's entry into the study, and this partner is the sole partner for that participant, will be allowed. The documentation of partner sterility can come from the site personnel s review of medical records, medical examination and/or semen analysis, or medical history interview provided by the participant or the partner. Self-reported documentation of reproductive potential should be entered in the source documents.

9. Participants who can impregnate a partner and who are engaging in sexual activity that could lead to pregnancy must agree to use condoms from 10 days prior to the first dose of the IPs, while receiving the IPs and during study follow up to avoid impregnating a partner who can get pregnant.

EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

1. History of AIDS-defining illness within 3 years prior to enrollment;

2. History of systemic corticosteroids (e.g., an equivalent dose of prednisone of > 20 mg daily for >14 days), immunosuppressive anti-cancer, interleukins, systemic interferons, systemic chemotherapy or other medications considered significant by the trial physician within the last 6 months;

3. Any clinically significant acute or chronic medical condition (e.g. such as autoimmune diseases, cirrhosis, active malignancy that may require systemic chemotherapy or radiation therapy), other than HIV infection, that in the opinion of the investigator would preclude participation;

4. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood. NOTE: Participants with a positive test for HCV antibody and a negative test for HCV RNA are eligible;

5. Participants with known hypersensitivity to any constituent of the investigational products;

6. Pregnancy or lactation;

7. ART initiated during acute infection (defined as p24, HIV nucleic acid amplification technique [NAAT], or HIV RNA PCR positive, and negative or indeterminate HIV antibody testing);

8. Laboratory abnormalities in the parameters listed below:

- Absolute neutrophil count < 1,000 cells/microliter

- Hemoglobin < 10 gm/dL

- Platelet count < 100,000 cells/microliter

- ALT > 1.5 x ULN

- AST > 1.5 x ULN

- Total bilirubin > 1.5 x ULN

- Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m^2

9. Any history of receipt of HIV-1 mAb therapy or HIV vaccine;

10. Participation in any clinical study of an investigational product within 12 weeks prior to study entry (day 0) or expected participation in such a study during this study;

11. Any approved or experimental non-HIV vaccination (e.g., SARS-CoV-2, hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment (day 0);

12. Inability to undergo leukapheresis due to poor venous access or other medical conditions;

13. Active drug or alcohol use or any other pattern of behavior that, in the opinion of the investigator, would interfere with adherence to study requirements.


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Citations:

Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, Lehmann C, Su(SqrRoot)(Degree)rez I, Oliveira TY, Lorenzi JCC, Cohen YZ, Wyen C, K(SqrRoot) mmerle T, Karagounis T, Lu CL, Handl L, Unson-O'Brien C, Patel R, Ruping C, Schlotz M, Witmer-Pack M, Shimeliovich I, Kremer G, Thomas E, Seaton KE, Horowitz J, West AP Jr, Bjorkman PJ, Tomaras GD, Gulick RM, Pfeifer N, F(SqrRoot) tkenheuer G, Seaman MS, Klein F, Caskey M, Nussenzweig MC. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26. PMID: 30258136; PMCID: PMC6166473.

Niessl J, Baxter AE, Mendoza P, Jankovic M, Cohen YZ, Butler AL, Lu CL, Dub(SqrRoot)(Copyright) M, Shimeliovich I, Gruell H, Klein F, Caskey M, Nussenzweig MC, Kaufmann DE. Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity. Nat Med. 2020 Feb;26(2):222-227. doi: 10.1038/s41591-019-0747-1. Epub 2020 Feb 3. PMID: 32015556; PMCID: PMC7018622.

Gaebler C, Nogueira L, Stoffel E, Oliveira TY, Breton G, Millard KG, Turroja M, Butler A, Ramos V, Seaman MS, Reeves JD, Petroupoulos CJ, Shimeliovich I, Gazumyan A, Jiang CS, Jilg N, Scheid JF, Gandhi R, Walker BD, Sneller MC, Fauci A, Chun TW, Caskey M, Nussenzweig MC. Prolonged viral suppression with anti-HIV-1 antibody therapy. Nature. 2022 Jun;606(7913):368-374. doi: 10.1038/s41586-022-04597-1. Epub 2022 Apr 13. PMID: 35418681; PMCID: PMC9177424.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Michael C. Sneller, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)



Catherine A. Seamon, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 8C404
10 Center Drive
Bethesda, Maryland 20892
(301) 402-3481
cseamon@cc.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT05612178

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