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Trial record 3 of 12 for:    sneller

Combination Therapy With 3BNC117 and 10-1074 in HIV-Infected Individuals

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ClinicalTrials.gov Identifier: NCT03571204
Recruitment Status : Recruiting
First Posted : June 27, 2018
Last Update Posted : September 13, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

Background:

Human immunodeficiency virus (HIV) affects the immune system. The main function of the immune system is protect you from infections and other diseases such as cancer. HIV attacks and cripples the immune system making people more susceptible to a variety of infections and cancers. Currently, the standard treatment for HIV infection is a daily administration of anti-HIV drugs. These drugs are called combination antiretroviral therapy (ART). ART is very effective at suppressing HIV, but does not cure HIV infection. ART must be taken continuously for life to be effective. ART can stop being effective if not taken correctly and can cause permanent side effects. Researchers want to see if two new products can control HIV infection without the use of ART. The products are the antibodies 3BNC117 and 10-1074.

Objective:

To see if 3BNC117 and 10-1074 are safe and can control HIV levels in the blood of people who are not taking ART or people who stop taking their ART during the study. .

Eligibility:

Adults ages 18-65 with HIV who are:

  • on ART and willing to stop treatment for at least 28 weeks
  • OR not taking ART with low levels of HIV in the blood

Design:

Participants will be screened with a physical exam, medical history, and blood, heart, and urine tests.

Participants will get the 2 study products or salt water (placebo). A thin tube will be placed in an arm vein. Each product will be given directly into the vein for about 1 hour.

To help collect blood cells to study in the laboratory, participants may have a procedure known as leukapheresis in which blood will be removed through a needle in the arm. Some of the white blood cells will be separated from the blood and used for research studies to see how 3BNC117 and 10-1074 effects HIV and the immune system. The rest of the blood will be returned to the person through another needle in the arm.

Participants will have 18 study visits over 28 weeks. They will repeat some screening tests. They may have leukapheresis again.

At 8 study visits, participants will get the study products or placebo.

All participants will be followed for at least 24 weeks after their last dose of the study infusions. Participants who are in the Group that stops ART will be monitored closely to make sure the levels of virus in their blood do not go to high. If at any time during this the study a person develops HIV-related symptoms, or if the viral levels go up to high levels for more than 4 weeks, ART will be restarted and no further infusions of 3BNC117 and 10-1074 will be given.


Condition or disease Intervention/treatment Phase
HIV Biological: 3BNC117 Biological: 10-1074 Other: Normal saline placebo Phase 1

Detailed Description:

Recent advances in antibody cloning technologies have led to the discovery of a number of highly potent and HIV-specific broadly neutralizing monoclonal antibodies (bNAbs) from B cells of HIV-infected individuals. It has been shown that certain bNAbs can prevent acquisition of the virus, suppress viral replication, delay and/or prevent plasma viral rebound following treatment interruption in Simian Immunodeficiency virus (SIV)-infected animals and block cell-to-cell transmission of laboratory-adapted HIV in vitro. In light of these encouraging outcomes, a number of clinical trials have been conducted in recent years in order to explore the feasibility of achieving sustained virologic suppression using a single bNAb in HIV-infected individuals following analytical treatment interruption (ATI). Despite the fact that repeated administration of a single bNAb was safe and well-tolerated, the vast majority of study subjects experienced plasma viral rebound following ATI, clearly demonstrating that successful passive immunotherapy will require different approach, including the use of a combination of 2 or more bNAbs to achieve extended periods of virologic suppression.

Given a major emphasis on current HIV research lies in the possibility of achieving ART-free virologic remission, it is of great interest to investigate whether a combination of potent HIV- specific bNAbs, such as 3BNC117 and 10-1074, can prevent plasma viral rebound in infected individuals upon discontinuation of ART or suppress viral replication in subjects who are not taking ART.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: An Exploratory Study of Combination Therapy With 3BNC117 and 10-1074 in HIV-Infected Individuals
Actual Study Start Date : September 10, 2018
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Group-1 active treatment
Group 1, 15 individuals who began ART during primary HIV-1 infection will be randomized to treatment with 3BNC117 plus 10-1074. Study staff and participants will be blinded to Group 1 treatment assignments.
Biological: 3BNC117
Both 3BNC117 and 10-1074 will be administered intravenously at 30 mg/kg dose level. Both study groups will receive 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy is 24 weeks; the duration may be shorter if criteria listed in section 3.1 are met. The dose of both 3BNC117 and 10- 1074 for this study is 30 mg/kg in 250 ml normal saline. The two antibodies will be mixed in separate bags of saline for sequential administration. To prepare an IV infusion, the pharmacist will calculate the total milligrams of each antibody needed, thaw the minimum number of vials needed to obtain the full dose and add the calculated total milligrams needed to a final volume of 250 ml of normal saline using good pharmacy practices to maintain sterility. The infusion solution must be used within 3 hours. Any unused portion of an antibody vial will not be used for another subject.

Biological: 10-1074
Both 3BNC117 and 10-1074 will be administered intravenously at 30 mg/kg dose level. Both study groups will receive 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy is 24 weeks; the duration may be shorter if criteria listed in section 3.1 are met. The dose of both 3BNC117 and 10- 1074 for this study is 30 mg/kg in 250 ml normal saline. The two antibodies will be mixed in separate bags of saline for sequential administration. To prepare an IV infusion, the pharmacist will calculate the total milligrams of each antibody needed, thaw the minimum number of vials needed to obtain the full dose and add the calculated total milligrams needed to a final volume of 250 ml of normal saline using good pharmacy practices to maintain sterility. The infusion solution must be used within 3 hours. Any unused portion of an antibody vial will not be used for another subject.

Placebo Comparator: Group-1 placebo
Group 1, 15 individuals who began ART during primary HIV-1 infection will be randomized to treatment with normal saline placebo. Study staff and participants willbe blinded to Group 1 treatment assignments.
Other: Normal saline placebo
8 infusions of placebo at weeks 0, 2, 4, 8, 12, 16, 20, and 24 will be administered. The total duration of therapy is 24 weeks; the duration may be shorter if criteria listed in section 3.1 are met. The placebo will be normal saline alone. The placebo will be in separate bags for sequential administration.

Experimental: Group-2 active treatment
Group 2, up to 15 viremic individuals not taking ARTwill receive 3BNC117 combined with 10-1074.
Biological: 3BNC117
Both 3BNC117 and 10-1074 will be administered intravenously at 30 mg/kg dose level. Both study groups will receive 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy is 24 weeks; the duration may be shorter if criteria listed in section 3.1 are met. The dose of both 3BNC117 and 10- 1074 for this study is 30 mg/kg in 250 ml normal saline. The two antibodies will be mixed in separate bags of saline for sequential administration. To prepare an IV infusion, the pharmacist will calculate the total milligrams of each antibody needed, thaw the minimum number of vials needed to obtain the full dose and add the calculated total milligrams needed to a final volume of 250 ml of normal saline using good pharmacy practices to maintain sterility. The infusion solution must be used within 3 hours. Any unused portion of an antibody vial will not be used for another subject.

Biological: 10-1074
Both 3BNC117 and 10-1074 will be administered intravenously at 30 mg/kg dose level. Both study groups will receive 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy is 24 weeks; the duration may be shorter if criteria listed in section 3.1 are met. The dose of both 3BNC117 and 10- 1074 for this study is 30 mg/kg in 250 ml normal saline. The two antibodies will be mixed in separate bags of saline for sequential administration. To prepare an IV infusion, the pharmacist will calculate the total milligrams of each antibody needed, thaw the minimum number of vials needed to obtain the full dose and add the calculated total milligrams needed to a final volume of 250 ml of normal saline using good pharmacy practices to maintain sterility. The infusion solution must be used within 3 hours. Any unused portion of an antibody vial will not be used for another subject.




Primary Outcome Measures :
  1. To evaluate safety and tolerability of multiple 3BNC117 and 10-1074doses [ Time Frame: Throughout the ATI / Infusion Phase ]

Secondary Outcome Measures :
  1. The rate of occurrence of grade 3 or higher AEs, including SAEs, that, per standard criteria are probably or definitely related to the test article. [ Time Frame: Throughout the study ]
  2. Difference between the treatment and placebo arms in the number of subjects in study Group 1 who experience rebound of plasma viremia and meet criteria to restart ART prior to study week 28. [ Time Frame: At study completion ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

General Inclusion Criteria for both Groups:

  1. Age 18-65 years old.
  2. HIV-1 infection and clinically stable.
  3. General good health and has an identified primary health care provider for medical management of HIV infection and is willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study.
  4. CD4+ T cell count >450 cells/mm(3) at screening.
  5. Laboratory values within pre-defined limits at screening:

    1. Absolute neutrophil count >1,000/mm(3).
    2. Hemoglobin levels >10.0 g/dL for men and >9.0 g/dL for women.
    3. Platelet count >100,000/mm(3).
    4. Estimated or a measured glomerular filtration rate >60 mL/min/1.73m(2) as determined by the National Institutes of Health (NIH) Clinical Center laboratory.
    5. AST and ALT levels of <2.5 times upper limit of normal (ULN), direct bilirubin within the normal range for the NIH Clinical Center laboratory.
  6. Willingness to have samples stored for future research.

    Inclusion criteria specific for Group 1:

  7. Institution of ART within 12 weeks of being diagnosed with primary HIV-1 infection
  8. Primary HIV-1 infection is defined as meeting at least one of the following criteria:

    1. Detectable plasma HIV-1 RNA levels of >2000 copies/mL with a negative result from an HIV-1 EIA, or
    2. Positive result from an HIV-1 EIA with a negative or indeterminate result from an HIV-1 western blot or another confirmatory antibody test that subsequently evolves to a confirmed positive result, or
    3. Negative result from an HIV-1 EIA within the past 4 months and HIV-1 RNA levels of >400,000 copies/mL, in the setting of a potential exposure to HIV-1.
    4. Negative result from an HIV-1 EIA within 6 months prior to a positive result from an HIV-1 EIA and an HIV-1 western blot or another confirmatory antibody test.
    5. Presence of low level of HIV antibodies as determined by having a positive EIA or a positive Western blot with a non-reactive detuned EIA according to a serologic testing algorithm for recent infection.
  9. Documentation of continuous ART treatment with suppression of plasma viral level below the limit of detection for greater than or equal to 1 years. Individuals with blips (i.e., detectable viral levels on ART) prior to screening may be included provided they satisfy the following criteria:

    1. The blips are <400 copies/mL, and
    2. Succeeding viral levels return to levels below the limit of detection on subsequent testing.
  10. Willingness to undergo ATI
  11. Willingness for both male and female subjects to agree to use barrier protection methods or abstinence during the ATI phase of the study to decrease the risk of HIV transmission.

    Inclusion criteria specific for Group 2:

  12. No ART within 24 months of screening.
  13. HIV plasma viremia between 200 and 5,000 copies/mL at screening AND at least two documented viral level greater than or equal to 200 copies/mL in the 12 months prior to screening.

At the screening visit, subjects considering enrollment in Group 2 will be advised that current guidelines recommend treatment of all individuals with HIV infection regardless of viral levels and CD4 counts.

Reproductive Risks

Contraception: The effects of 3BNC117 and 10-1074 on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate pregnancy prevention. This includes the use an effective method of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) for the study duration. Subjects should also agree to use a male or female condom while off ART. Pregnancy prevention must be practiced continuously for the duration of study participation. Females of childbearing-age must have a negative pregnancy test result prior to receiving each infusion of 3BNC117/10-1074. During the course of the study, if a female subject, or the partner of a male subject suspects or in fact becomes pregnant, the effected subject should inform the study staff immediately, as well as the woman s primary care physician.

EXCLUSION CRITERIA:

  1. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen

    (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.

  2. HIV immunotherapy or vaccine(s) received within 1 year prior to screening.
  3. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment.
  4. Receipt of other investigational study agent within 28 days of enrollment.
  5. Any active malignancy that may require systemic chemotherapy or radiation therapy.
  6. Systemic immunosuppressive medications received within 3 months prior to enrollment (Not excluded: [1] corticosteroid nasal spray or inhaler; [2] topical corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur [length of therapy less than or equal to10 days, with completion in greater than or equal to 30 days prior to enrollment]).
  7. History or other clinical evidence of:

    1. Significant or unstable cardiac or cerebrovascular disease (e.g., angina, congestive heart failure, recent stroke or myocardial infarction).
    2. Severe illness, malignancy, immunodeficiency other than HIV, or any other condition that, in the opinion of the investigator, would make the subject unsuitable for the study.
  8. 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.
  9. Pregnancy or breast-feeding at time of screening.
  10. Documented multiclass antiretroviral drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study (Group 1 only).

Co-enrollment Guidelines: Co-enrollment in other trials is restricted to observational studies or those evaluating the use of a licensed medication and is subject to approval of the principal investigator (PI).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03571204


Contacts
Contact: Kathleen R Gittens (301) 435-8003 gittenskr@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Michael C Sneller, M.D. National Institute of Allergy and Infectious Diseases (NIAID)

Additional Information:
Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03571204     History of Changes
Other Study ID Numbers: 180115
18-I-0115
First Posted: June 27, 2018    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 4, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Treatment Interruption
Neutralizing Monoclonal Antibody

Additional relevant MeSH terms:
Antibodies
Immunologic Factors
Physiological Effects of Drugs