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10E8.4/iMab Bispecific Antibody in HIV-uninfected and HIV-infected Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03875209
Recruitment Status : Recruiting
First Posted : March 14, 2019
Last Update Posted : April 9, 2019
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
International AIDS Vaccine Initiative
The Emmes Company, LLC
Information provided by (Responsible Party):
Aaron Diamond AIDS Research Center

Brief Summary:

Many HIV-infected individuals mount a broad neutralizing serologic response 2-3 years after infection. Broadly neutralizing antibodies might play an important role in protection from acquisition of HIV infection because they can protect macaques from infection, and the presence of anti-HIV antibodies was the only positive correlate of protection in an HIV vaccine efficacy trial (RV144 trial). HIV neutralizing antibodies also have the potential to alter the course of HIV infection in humans. Therefore, these antibodies might be useful to both prevent and treat HIV-1 infection.

This is a phase 1 dose escalating clinical trial to evaluate the safety, tolerability, pharmacokinetics and the antiretroviral effects of a novel bispecific monoclonal antibody 10E8.4/iMab in HIV-infected and HIV-uninfected individuals. The study will be conducted as a multi-center study at the Columbia University Medical Center in New York City and the Orlando Immunology Center in Orlando FL.


Condition or disease Intervention/treatment Phase
HIV-1-infection Biological: 10E8.4/iMab Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Dose escalation, open-label (IV or SC administration), placebo-controlled (SC administration)
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Participants in SC dosing Arm 4 Groups J and K will be blinded as will providers and members of the study site team. Study pharmacists will not be blinded. Safety monitoring committee will not be blinded. All participants treated IV and participants treated 1 mg/kg SC will not be masked (open-label).
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of the Bispecific Antibody 10E8.4/iMab in HIV-1-infected and Uninfected Individuals
Actual Study Start Date : April 5, 2019
Estimated Primary Completion Date : October 30, 2020
Estimated Study Completion Date : April 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Arm 1: 10E8.4/iMab IV or SC HIV-
Arm 1; Groups A-C; 3 dosing groups: HIV-uninfected individuals
Biological: 10E8.4/iMab
bispecific monoclonal antibody

Experimental: Arm 2: 10E8.4/iMab IV HIV-
Arm 2; Groups D-F; 3 dosing groups: HIV-uninfected individuals
Biological: 10E8.4/iMab
bispecific monoclonal antibody

Experimental: Arm 3: 10E8.4/iMab IV HIV+
Arm 3; Groups G-I; 3 dosing groups: HIV-infected individuals with HIV-1 RNA levels between 2,000 and 100,000 copies/mL and CD4>350 cells/mm3
Biological: 10E8.4/iMab
bispecific monoclonal antibody

Experimental: Arm 4: 10E8.4/iMab SC HIV-
Arm 4; Groups J and K: HIV-uninfected individuals
Biological: 10E8.4/iMab
bispecific monoclonal antibody




Primary Outcome Measures :
  1. Safety of the highest single intravenous dose of 10E8.4/iMab in HIV uninfected individuals. Safety of a single dose of intravenous dose of 10E8.4/iMab in HIV uninfected individuals [ Time Frame: 24 weeks ]
    Percentage of subjects experiencing a dose limiting toxicity defined as a Grade 3 or 4 adverse events as per the toxicity grading scale for healthy volunteers enrolled in preventative vaccine trials

  2. Safety of the highest single intravenous dose of 10E8.4/iMab in HIV infected individuals Safety of a single dose of intravenous dose of 10E8.4/iMab in HIV uninfected individuals [ Time Frame: 24 weeks ]
    Percentage of subjects experiencing a dose limiting toxicity defined as a Grade 3 or more adverse event as per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events v 2.1

  3. Injection site reactions associated with a single subcutaneous injection of 10 E8.4/iMab in HIV uninfected individuals [ Time Frame: 24 weeks ]
    Percentage of injections associated with a Grade 2 or greater injection site reaction as per the toxicity grading scale for healthy volunteers enrolled in preventative vaccine trials

  4. Systemic infusion reaction associated with the intravenous administration of any dose of 10E8.4/iMab [ Time Frame: 24 weeks ]
    Percentage of subjects receiving intravenous 10E8.4/iMab as per CTCAE version 5.0.


Secondary Outcome Measures :
  1. Antiviral activity of the highest single dose of 10E8.4/iMab given intravenously to viremic HIV infected individuals [ Time Frame: 7 days ]
    changes in log HIV-1 RNA levels from baseline

  2. Antiviral activity of the highest single dose of 10E8.4/iMab given intravenously to viremic HIV infected individuals [ Time Frame: 14 days ]
    changes in log HIV-1 RNA levels from baseline

  3. Antiviral activity of the highest single dose of 10E8.4/iMab given intravenously to viremic HIV infected individuals [ Time Frame: 28 days ]
    changes in log HIV-1 RNA levels from baseline

  4. Serum levels 10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals [ Time Frame: 7 days ]
    levels of 10E8.4/iMab expressed in ng/mL serum

  5. Serum levels of 10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals [ Time Frame: 14 days ]
    levels of 10E8.4/iMab expressed in ng/mL serum

  6. Serum levels of10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals. [ Time Frame: 28 days ]
    levels of 10E8.4/iMab expressed in ng/mL serum

  7. Serum levels of10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals. [ Time Frame: 56 days ]
    levels of 10E8.4/iMab expressed in ng/mL serum

  8. Serum levels of 10E8.4/iMab after the highest single dose of 10E8..4/iMab given subcutaneously to HIV uninfected individuals [ Time Frame: 7 days ]
    levels of 10E8.4/iMab expressed in ng/mL serum

  9. Serum levels of 10E8.4/iMab after the highest single dose of 10E8..4/iMab given subcutaneously to HIV uninfected individuals [ Time Frame: 14 days ]
    levels of 10E8.4/iMab expressed in ng/mL serum

  10. Serum levels of 10E8.4/iMab after the highest single dose of 10E8..4/iMab given subcutaneously to HIV uninfected individuals [ Time Frame: 28 days ]
    levels of 10E8.4/iMab expressed in ng/mL serum

  11. Serum levels of 10E8.4/iMab after the highest single dose of 10E8..4/iMab given subcutaneously to HIV uninfected individuals [ Time Frame: 56 days ]
    levels of 10E8.4/iMab expressed in ng/mL serum

  12. Percentage of subjects developing antibodies to 10E8.4/iMab after any single intravenous or subcutaneous dose of 10E8.4/iMab [ Time Frame: 84 days ]
    Percent of study participants



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for HIV uninfected volunteers: Arms 1, 2 and 4:

  • Healthy volunteers born male and female as assessed by medical history and physical examination
  • Aged >18 and <60 years at the time of screening
  • Ability and willingness to provide written informed consent
  • Willingness to comply with protocol schedule
  • Willingness to undergo HIV-1 testing
  • Non-reactive 4th generation point of care HIV-1 test at screening
  • Hepatitis B Surface antigen negative
  • Hepatitis C antibody negative, or if reactive, Hepatitis C RNA undetectable in plasma
  • Volunteers born female of reproductive potential, sexually active with a male sex partner must agree to use one effective method of contraception from the time of signing the consent to completion of the study and agree to pregnancy testing as per the schedule of events.
  • Study participants born female with reproductive potential are defined as pre-menopausal volunteers born female who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Volunteers born female are considered menopausal if they have not had a menses for at least 12 months and have an FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.

Inclusion Criteria for HIV-1-Infected Viremic Subjects: Arm 3

  • Aged >18 and <60 years at the time of screening
  • Ability and willingness to provide written informed consent
  • Willingness to comply with protocol schedule
  • Willingness to undergo HIV-1 testing
  • Reactive 4th generation point of care HIV-1 test at screening
  • Plasma HIV-1 RNA levels > 2,000 copies/mL and < 100,000 copies/mL in subjects who are either:

    • ART-naïve
    • ART-experienced and in consultation with their primary provider have discontinued therapy for at least 8 weeks
    • ART-experienced, clinically stable and without changes to their ART regimen for at least 8 weeks
  • Current CD4+ T cell count > 350 cells/mm3 and a nadir CD4+ T cell count > 250 cells/mm3
  • Agrees not to begin or change antiretroviral therapy for 6 weeks after 10E8.4/iMab infusion despite a clear explanation of current DHHS guidelines
  • Hepatitis B Surface antigen negative
  • Hepatitis C antibody negative or if reactive Hepatitis C RNA undetectable in plasma
  • Volunteers born female of reproductive potential, sexually active with a male sex partner agree to use one effective method of contraception from the time of signing the consent to completion of the study and agree to pregnancy testing as per the schedule of events.
  • Study participants born female with reproductive potential are defined as pre-menopausal volunteers born female who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Volunteers born female are considered menopausal if they have not had a menses for at least 12 months and have an FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.

Exclusion Criteria for HIV uninfected volunteers: Arms 1, 2 and 4:

  • Confirmed HIV-1 infection
  • At high risk of HIV-1 infection as defined by:

    • Unprotected intercourse with a casual or HIV-infected partner over the past 12 months
    • In a serodisconcordant relationship with an HIV-1 infected partner
    • A diagnosed new sexually transmitted infection within the past 12 months
    • Exchange of money or drugs for sex in the last 12 months
    • More than 2 sexual partners, defined as insertive or receptive vaginal or anal intercourse, within the past 6 months
  • Weight above 100 kg at screening. Note that subjects above 80 kg may not be randomized into the SC dosing group in Arm 4.
  • Any acute or chronic medical condition that in the opinion of the investigator would preclude participation
  • Immunodeficiency or chronic autoimmune disease
  • Intravenous drug use
  • Excessive use of alcohol or recreational drugs that in the opinion of the investigator would preclude participation.
  • Decompensated psychiatric illness
  • Need for chronic immunotherapy including systemic corticosteroids, other monoclonal antibody therapy, or immunosuppressive drugs
  • If born female, pregnant, lactating or planning on becoming pregnant over the study period
  • Any of the following laboratory parameters:

    • Hemoglobin <10.0 g/dL
    • Absolute neutrophil count <1,000/mm3
    • Absolute lymphocyte count <500/mm3
    • Platelet count <100,000/mm3
    • PT >1.25xULN
    • PTT >1.66xULN
    • Creatinine >1.25x Upper limit of normal (ULN)
    • AST >1.5X ULN
    • ALT >1.5X ULN
    • Glucose (non-fasting) >160mg/dL
    • Proteinuria: 2+ or greater
    • Hematuria: >10 RBC per high power field
    • Serum calcium < 8.5 mg/dL or >10.2 mg/dL
    • Serum PTH levels <10 pg/mL or >65 pg/mL
  • Any vaccine administration within 14 days of study entry
  • Experimental HIV-1 vaccine in past (active arm of an HIV-1 vaccine trial if applicable)
  • Previous receipt of an experimental mAb to HIV-1 in a research study
  • History of severe allergic reactions to drugs, vaccines, or drug infusion
  • Participation in another investigational clinical trial within the past 12 weeks or anticipated during the course of the current study

Exclusion Criteria for HIV-1-Infected Viremic Subjects: Arm 3

  • Any acute or chronic medical condition that in the opinion of the investigator would preclude participation
  • A history of virologic failure of two or more combination antiretroviral treatment regimens. A regimen switch due solely to intolerance and not virologic failure does not qualify as a failed regimen.
  • Weight above 100 kg at the time of screening.
  • Intravenous drug use
  • Excessive use of alcohol or recreational drugs that in the opinion of the investigator would preclude participation
  • Decompensated psychiatric illness
  • Need for chronic immunotherapy including systemic corticosteroids, other monoclonal antibody therapy, or immunosuppressive drugs
  • If born female, pregnant, lactating or planning on becoming pregnant over the study period
  • Any of the following laboratory parameters

    • Hemoglobin <10.0 g/dL
    • Absolute neutrophil count <1,000/mm3
    • Absolute lymphocyte count <500/mm3
    • Platelet count <100,000/mm3
    • PT >1.25xULN
    • PTT >1.66xULN
    • Creatinine >1.25x Upper limit of normal (ULN)
    • AST >1.5X ULN
    • ALT >1.5X ULN
    • Glucose (non-fasting) >160mg/dL
    • Proteinuria: 2+ or greater
    • Hematuria: >10 RBC per high power field
    • Serum calcium < 8.5 mg/dL and >10.2 mg/dL
    • Serum PTH level <10 pg/mL or >65 pg/mL
  • Any vaccine administration within 14 days of study entry
  • Experimental HIV-1 vaccine in past (active arm of an HIV-1 vaccine trial if applicable)
  • Participation in a research study of a neutralizing mAb to HIV-1
  • History of severe allergic reactions to drugs, vaccines, or drug infusion
  • Participation in another investigational clinical trial within the past 12 weeks or anticipated during the course of the current study

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): NCT03875209


Contacts
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Contact: Yang Luo, PhD 212-448-5067 yluo@adarc.org
Contact: Martin Markowitz, MD 212-448-5020 mmarkowitz@adarc.org

Locations
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United States, Florida
Orlando Immunology Center Not yet recruiting
Orlando, Florida, United States, 32803
Contact: Jocelyn M.    407-647-3960 ext 2133    RESEARCH@OICORLANDO.COM   
United States, New York
Columbia University Research Unit Recruiting
New York, New York, United States, 10032
Contact: Brett Gray, NP    212-305-1570    bg2168@cumc.columbia.edu   
Contact: Magdalena Sobieszczyk, MD, MPH    212-305-7185    mes52@cumc.columbia.edu   
Sponsors and Collaborators
Aaron Diamond AIDS Research Center
Bill and Melinda Gates Foundation
International AIDS Vaccine Initiative
The Emmes Company, LLC
Investigators
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Principal Investigator: David D. Ho, MD Aaron Diamond AIDS Research Center

Publications:
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Responsible Party: Aaron Diamond AIDS Research Center
ClinicalTrials.gov Identifier: NCT03875209     History of Changes
Other Study ID Numbers: ABA-0101
First Posted: March 14, 2019    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Antibodies
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs