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Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults

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ClinicalTrials.gov Identifier: NCT03387150
Recruitment Status : Recruiting
First Posted : December 29, 2017
Last Update Posted : September 13, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, and serum concentrations of a human monoclonal antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and routes to healthy, HIV-uninfected adults.

Condition or disease Intervention/treatment Phase
HIV Infections Biological: VRC07-523LS Biological: Placebo Phase 1

Detailed Description:

This study will evaluate the safety, tolerability, and serum concentrations of a human monoclonal antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and routes to healthy, HIV-uninfected adults.

Participants will be randomly assigned to one of six groups. Participants in Group 1 will receive 2.5 mg/kg of VRC07-523LS by intravenous (IV) infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 2 will receive 5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 3 will receive 20 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 4 will receive 2.5 mg/kg of VRC07-523LS by subcutaneous (SC) injection at Weeks 0, 16, 32, 48, and 64. Participants in Group 5 will receive 5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64. Participants in Group 6 will receive 2.5 mg/kg of VRC07-523LS or placebo by intramuscular (IM) injection at Weeks 0, 16, 32, 48, and 64.

Participants will attend numerous study visits throughout the course of the study, beginning at Week 0 through Week 112. Visits may include physical examinations, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Multicenter, Randomized, Partially Blinded Phase 1 Clinical Trial to Evaluate the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults
Actual Study Start Date : February 2, 2018
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Group 1: VRC07-523LS
Participants in Group 1 will receive 2.5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.
Biological: VRC07-523LS
Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in
Other Name: VRC-HIVMAB075-00-AB

Experimental: Group 2: VRC07-523LS
Participants in Group 2 will receive 5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.
Biological: VRC07-523LS
Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in
Other Name: VRC-HIVMAB075-00-AB

Experimental: Group 3: VRC07-523LS
Participants in Group 3 will receive 20 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.
Biological: VRC07-523LS
Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in
Other Name: VRC-HIVMAB075-00-AB

Experimental: Group 4: VRC07-523LS
Participants in Group 4 will receive 2.5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64.
Biological: VRC07-523LS
Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in
Other Name: VRC-HIVMAB075-00-AB

Experimental: Group 5: VRC07-523LS
Participants in Group 5 will receive 5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64.
Biological: VRC07-523LS
Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in
Other Name: VRC-HIVMAB075-00-AB

Experimental: Group T6 VRC07-523LS
Participants in Group T6 will receive 2.5 mg/kg of VRC07-523LS by IM injection at Weeks 0, 16, 32, 48, and 64.
Biological: VRC07-523LS
Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in
Other Name: VRC-HIVMAB075-00-AB

Placebo Comparator: Group P6: Placebo
Participants in Group P6 will receive 2.5 mg/kg of placebo by IM injection at Weeks 0, 16, 32, 48, and 64.
Biological: Placebo
Sodium Chloride for Injection USP, 0.9%; administered by IM injection




Primary Outcome Measures :
  1. Frequency of local Solicited Adverse Events (AEs) [ Time Frame: Measured through Week 112 ]
    Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 dated July 2017

  2. Frequency of systemic Solicited Adverse Events (AEs) [ Time Frame: Measured through Week 112 ]
    Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 dated July 2017

  3. Frequency of Unsolicited AEs [ Time Frame: Measured through Week 112 ]
    Categorized by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class and preferred terms

  4. Frequency of Serious Adverse Events (SAEs) [ Time Frame: Measured through Week 112 ]
    Categorized by MedDRA System Organ Class and preferred terms

  5. Frequency of AEs of special interest (AESI) [ Time Frame: Measured through Week 112 ]
    Categorized by MedDRA System Organ Class and preferred terms

  6. Number of participants with early discontinuation of study product administration [ Time Frame: Measured through Week 112 ]
    Tabulated by reason and treatment arm

  7. Serum concentrations of VRC07-523LS [ Time Frame: Measured through Week 112 ]
    Measured by binding activity among participants who received all scheduled product administrations


Secondary Outcome Measures :
  1. Serum concentrations of VRC07-523LS [ Time Frame: Measured through Week 112 ]
    Measured by binding activity for all groups in all participants regardless of how many product administrations they received

  2. Serum concentration of anti-drug antibody (ADA) in each group [ Time Frame: Measured through Week 112 ]
    ADA measured using the Meso Scale Discovery (MSD) platform with VRC07-523LS as the target antigen

  3. Magnitude of serum neutralizing activity in each group [ Time Frame: Measured through Week 72 ]
    Measured against a panel of Tier 2 viruses that exhibit a range of known sensitivities to VRC07-523LS

  4. Magnitude of neutralization compared to serum concentration and known IC50 of VRC07-523LS for each isolate [ Time Frame: Measured through Week 72 ]
    As measured by HIV-1-specific neutralizing antibody (nAb) assays



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

General and Demographic Criteria

  • Age of 18 to 50 years
  • Access to a participating clinical research site (CRS) and willingness to be followed for the planned duration of the study
  • Ability and willingness to provide informed consent
  • Assessment of understanding: 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
  • Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit
  • Good general health as shown by medical history, physical exam, and screening laboratory tests

HIV-Related Criteria:

  • Willingness to receive HIV test results
  • Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
  • Assessed by the clinic staff as being at 'low risk' for HIV infection and committed to maintaining behavior consistent with those criteria through the last required protocol clinic visit (see the protocol for more information).

Laboratory Inclusion Values

Hemogram/Complete Blood Count (CBC)

  • Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were assigned female sex at birth, greater than or equal to 13.0 g/dL for volunteers who were assigned male sex at birth. For transgender participants who have been on hormone therapy for more than 6 consecutive months, determine hemoglobin eligibility based on the gender with which they identify (ie, a transgender female who has been on hormone therapy for more than 6 consecutive months should be assessed for eligibility using the hemoglobin parameters for volunteers assigned female sex at birth).
  • White blood cell (WBC) count equal to 2,500 to 12,000 cells/mm^3
  • WBC differential either within institutional normal range or with site physician approval
  • Platelets equal to 125,000 to 550,000/mm^3

Chemistry

  • Chemistry panel: Alanine aminotransferase (ALT) less than 1.25 times the institutional upper limit of normal and creatinine less than or equal to institutional upper limits of normal.

Virology

  • Negative HIV-1 and -2 blood test: US volunteers must have a negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA). Non-US sites may use locally available assays that have been approved by HVTN and HIV Prevention Trials Network (HPTN) Laboratory Operations.
  • Negative Hepatitis B surface antigen (HBsAg)
  • Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive

Urine

  • Negative or trace urine protein

Reproductive Status

  • Volunteers who were assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to study product administration on the day of initial study infusion/injection. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.
  • Reproductive status: A volunteer who was assigned female sex at birth must:

    • Agree to use effective contraception (see protocol for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using the following methods:
    • Condoms (male or female) with or without a spermicide,
    • Diaphragm or cervical cap with spermicide,
    • Intrauterine device (IUD),
    • Hormonal contraception, or
    • Any other contraceptive method approved by the HVTN 127/HPTN 087 Protocol Safety Review Team (PSRT)
    • Successful vasectomy in any partner assigned male sex at birth (considered successful if a volunteer reports that a partner assigned male sex at birth 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 reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;
    • Or plan to be sexually abstinent until at least 6 months following the last study product administration.
  • Volunteers who were assigned female sex at birth must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

Exclusion Criteria:

General

  • Weight greater than 115 kg
  • Blood products received within 120 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 127/HPTN 087 PSRT
  • Investigational research agents received within 30 days before first study product administration
  • Intent to participate in another study of an investigational research agent or any other study that requires non-Network HIV antibody testing during the planned duration of the HVTN 127/HPTN 087 study
  • Pregnant or breastfeeding

Vaccines and other Injections

  • HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 127/HPTN 087 PSRT will determine eligibility on a case-by-case basis.
  • Previous receipt of humanized or human mAbs, whether licensed or investigational; the HVTN 127/HPTN 087 PSRT will determine eligibility on a case-by-case basis.
  • Previous receipt of monoclonal antibodies VRC01, VRC01LS, or VRC07-523LS

Immune System

  • Immunosuppressive medications received within 30 days before first injection or infusion (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral prednisone or equivalent at doses less than 2 mg/kg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment)
  • Serious adverse reactions to VRC07-523LS formulation components, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain
  • Immunoglobulin received within 90 days before first injection or infusion, unless eligibility for earlier enrollment is determined by the HVTN 127/HPTN 087 PSRT
  • Autoimmune disease (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate Solicited and Unsolicited adverse event (AE) assessments)
  • Immunodeficiency

Clinically significant medical conditions

  • 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:

    • A process that would affect the immune response,
    • A process that would require medication that affects the immune response,
    • Any contraindication to repeated injections, 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.
  • Any medical, psychiatric, occupational, or other condition 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 volunteer's ability to give informed consent
  • Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
  • Current anti-tuberculosis (TB) therapy
  • Asthma other than mild or moderate, 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 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;
    • Needed emergency care, urgent care, hospitalization, or intubation for asthma.
  • Diabetes mellitus type 1 or type 2 (Not excluded: type 2 cases controlled with diet alone or a history of isolated gestational diabetes.)
  • 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 as consistently less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg diastolic. For these volunteers, blood pressure must be less than or equal to 140 mm Hg systolic and less than or equal to 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 greater than or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or equal to 100 mm Hg at enrollment.
  • Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
  • Malignancy (Not excluded from participation: 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)
  • Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
  • Asplenia: any condition resulting in the absence of a functional spleen
  • History of hereditary angioedema, acquired angioedema, or idiopathic angioedema

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): NCT03387150


Locations
United States, Alabama
Alabama CRS Recruiting
Birmingham, Alabama, United States, 35294
Contact: Pamela Cunningham, R.N., B.S.N., M.P.H.    205-975-2841    pamelacunningham@uabmc.edu   
United States, Georgia
The Ponce de Leon Center CRS Recruiting
Atlanta, Georgia, United States, 30308-2012
Contact: Ericka Patrick, M.S.N.    404-616-6313    erpatri@emory.edu   
United States, Massachusetts
Brigham and Women's Hospital Vaccine CRS (BWH VCRS) Recruiting
Boston, Massachusetts, United States, 02115-6110
Contact: Jose H. Licona, M.D.    617-525-9433    jlicona@partners.org   
Fenway Health (FH) CRS Recruiting
Boston, Massachusetts, United States, 02215-4302
Contact: Marcy Gelman, R.N., M.S.N., M.P.H., A.R.N.P.    617-927-6021    mgelman@fenwayhealth.org   
United States, New York
Columbia P&S CRS Recruiting
New York, New York, United States, 10032-3732
Contact: Steven Palmer, P.A. -C    212-342-2958    sp500@cumc.columbia.edu   
United States, North Carolina
Chapel Hill CRS Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Becky Straub, B.S.N., M.P.H.    919-843-9975    bstraub@med.unc.edu   
Switzerland
Lausanne Vaccine and Immunotherapy Center CRS Recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: Rosemary Hottinger    41-21-3149282    Rosemary.Hottinger@chuv.ch   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Stephen Walsh Brigham and Women's Hospital
Study Chair: Cynthia Gay University of North Carolina, Chapel Hill

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03387150     History of Changes
Other Study ID Numbers: HVTN 127/HPTN 087
38458 ( Registry Identifier: DAIDS-ES Registry Number )
First Posted: December 29, 2017    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 2018

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

Additional relevant MeSH terms:
HIV Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs