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Evaluating the Safety, Pharmacokinetics, and Anti-Viral Activity of VRC01 and VRC01LS in the Serum and Mucosa of Healthy, HIV-Uninfected Adults

This study is currently recruiting participants.
Verified October 2017 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02797171
First Posted: June 13, 2016
Last Update Posted: October 26, 2017
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.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose
This study will evaluate the safety, pharmacokinetics, and antiviral activity of VRC-HIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB (VRC01LS) in the serum and mucosa of healthy, HIV-uninfected adults.

Condition Intervention Phase
HIV Infections Biological: VRC01 Biological: VRC01LS Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 1 Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Anti-Viral Activity of VRCHIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB (VRC01LS) in the Serum and Mucosa of Healthy, HIV-Uninfected Adult Participants

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency of local and systemic reactogenicity events [ Time Frame: Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in) ]
    Based on assessment of systemic symptoms that include increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, pruritus, diarrhea, and vomiting and local symptoms that include pain and/or tenderness proximal to the infusion site.

  • Frequency of adverse events (AEs) [ Time Frame: Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in) ]
    All AEs are graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.

  • Frequency of serious adverse events (SAEs) [ Time Frame: Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in) ]
    All AEs are graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.

  • Rates of participant discontinuation [ Time Frame: Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in) ]
    Tabulated by reason for discontinuation and treatment arm

  • Serum concentration of VRC01 out to Month 6 after the last infusion (for Groups 1, 2, and 4) [ Time Frame: Measured through 6 months after the last infusion ]
    Determined by laboratory assays

  • Levels of VRC01 in genital and rectal secretions, as well as cervical, vaginal, and rectal tissues (for Groups 1, 2, and 4) [ Time Frame: Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in) ]
    Determined by laboratory assays


Secondary Outcome Measures:
  • Ex vivo inhibition of HIV-1 infectivity in tissue biopsies (for Groups 1, 2, and 3) [ Time Frame: Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in) ]
    Determined from mucosal secretion and biopsy samples


Estimated Enrollment: 74
Actual Study Start Date: March 1, 2017
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Participants will receive 10 mg/kg of VRC01 at Months 0, 2, 4, and 6.
Biological: VRC01
Administered by intravenous (IV) infusion
Other Name: VRC-HIVMAB060-00-AB
Experimental: Group 2
Participants will receive 30 mg/kg of VRC01 at Months 0, 2, 4, and 6.
Biological: VRC01
Administered by intravenous (IV) infusion
Other Name: VRC-HIVMAB060-00-AB
Experimental: Group 3
Participants will receive 30 mg/kg of VRC01LS at Months 0, 3, and 6.
Biological: VRC01LS
Administered by intravenous (IV) infusion
Other Name: VRC-HIVMAB080-00-AB
Experimental: Group 4
Participants will receive 30 mg/kg of VRC01 at Month 0.
Biological: VRC01
Administered by intravenous (IV) infusion
Other Name: VRC-HIVMAB060-00-AB
Experimental: Group 5
Participants will receive 30 mg/kg of VRC01LS at Month 0.
Biological: VRC01LS
Administered by intravenous (IV) infusion
Other Name: VRC-HIVMAB080-00-AB

Detailed Description:

This study will evaluate two experimental human monoclonal antibodies (mAbs): VRC-HIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB (VRC01LS). VRC01LS is designed to have a longer half-life than VRC01. The purpose of this study is to evaluate the safety, pharmacokinetics, and antiviral activity of VRC01 and VRC01LS in the serum and mucosa of healthy, HIV-uninfected adults.

This study will enroll healthy, HIV-uninfected adults into five groups. At various time points during the study, participants in Groups 1, 2, and 4 will receive intravenous (IV) infusions of VRC01, and participants in Groups 3 and 5 will receive IV infusions of VRC01LS. Participants in Groups 1, 2, and 3 will attend 13 to 14 study visits over about 1 to 1 ½ years; participants in Groups 4 and 5 will attend 7 to 9 study visits over about 6 months to 1 year. At certain time points, study visits will include physical examinations, blood collection, urine collection, and interviews and questionnaires. At other time points, depending on group assignment and gender, visits will also include collection of cervicovaginal secretions, rectal secretions, and semen; and cervical, vaginal, and rectal biopsies.

  Eligibility

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.


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
  • Weight less than or equal to 115 kg
  • Access to a participating HIV Vaccine Trials Network (HVTN) 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; completes a questionnaire prior to enrollment 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 study 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 [low risk guidelines are found on the protocol home page on the HVTN Members' site (https://members.hvtn.org/protocols/hvtn116)] and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit

Laboratory Inclusion Values:

Hemogram/CBC

  • Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
  • White blood cell count equal to 2,500 to 12,000 cells/mm^3
  • Total lymphocyte count greater than or equal to 800 cells/mm^3
  • Remaining 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), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal; creatinine less than or equal to institutional upper limit of normal

Virology

  • Negative HIV-1 and -2 blood test: U.S. volunteers must have a negative Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA). Non-U.S. sites may use locally available assays that have been approved by HVTN 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

  • Normal urine:

    • Negative urine glucose, and
    • Negative or trace urine protein, and
    • Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range)

Reproductive Status:

  • Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to initial biopsy for groups 1-3 and prior to initial infusion for groups 4-5 on the day of enrollment. Persons who are NOT of reproductive potential due to having undergone bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.

Reproductive Status:

United States:

A volunteer who was born female must:

  • Agree to consistently use effective contraception (see the 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 116 Protocol Safety Review Team (PSRT)
    • Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner 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 had a bilateral oophorectomy, or tubal ligation;
  • Or be sexually abstinent.

South Africa:

A volunteer who was born female must:

  • Agree to consistently use effective contraception (see the 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 for participants in South Africa is defined as using 2 methods of birth control.

ONE barrier contraceptive method:

  • Condoms (male or female)
  • Diaphragm or cervical cap

PLUS ONE of the following methods:

  • Intrauterine device (IUD),
  • Hormonal contraception, or
  • Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner 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
  • Any other contraceptive method approved by the HVTN 116 PSRT

Or not be of reproductive potential, such as having had a bilateral oophorectomy, or tubal ligation;

Or be sexually abstinent.

  • Volunteers who were born female 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

Mucosal Specimen Collection

  • Volunteers 21 years of age and older who were born female: Pap smear (verified by medical records) is required within:

    • the 3 years prior to enrollment with the latest result reported as normal or ASCUS (atypical squamous cells of undetermined significance), OR
    • the 5 years prior to enrollment, with the latest result reported as normal, or ASCUS with no evidence of high risk HPV.
    • If no Pap smear was done within the last 3 years (or within the last 5 years, if high risk HPV testing was performed), the volunteer must be willing to undergo a Pap smear with the result reported (verified by medical records) as normal or ASCUS prior to sample collection.
  • Willing to have mucosal secretions and tissue biopsies collected
  • Willing to abstain from sexual intercourse for the required period after each biopsy collection

Exclusion Criteria:

General

  • Blood products received within 120 days before first infusion, unless eligibility for earlier enrollment is determined by the HVTN 116 PSRT
  • Investigational research agents received within 30 days before first infusion
  • Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 116 study
  • Pregnant or breastfeeding
  • Active duty U.S. military personnel with the potential of being deployed during the study

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 116 PSRT will determine eligibility on a case-by-case basis.
  • Non-HIV experimental vaccine(s) received within the last 6 months in a prior vaccine trial. Exceptions may be made for some vaccines and vaccine trials. For volunteers who have received an experimental vaccine(s) less than 6 months ago, eligibility for enrollment will be determined by the HVTN 116 PSRT on a case-by-case basis.
  • Live attenuated vaccines other than influenza vaccine received within 10 days before first infusion or scheduled within 10 days after first infusion (e.g., measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)
  • Previous receipt of humanized or human mAbs whether licensed or investigational

Immune System

  • Immunosuppressive medications received within 30 days before first infusion. (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; or [3] topical corticosteroids for mild, uncomplicated dermatitis)
  • Serious adverse reactions to VRC01 and VRC01LS formulation components such as sodium citrate, sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain
  • Autoimmune disease (Not exclusionary: mild, well-controlled psoriasis)
  • Immunodeficiency

Clinically Significant Medical Conditions

  • Untreated or incompletely treated syphilis infection
  • 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 infusions or blood draws, including perceived inability to establish venous access
    • A condition that requires regular use of any anticoagulant medications (not including aspirin or NSAIDs),
    • 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 for which signs or symptoms could be confused with reactions to study product, or
    • Any condition specifically listed among the exclusion criteria below.
  • 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 reactogenicity, 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) prophylaxis or therapy
  • Asthma other than mild, 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 moderate/high dose inhaled corticosteroids, or
    • In the past year has 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, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
  • Thyroidectomy, or thyroid disease unless well controlled (normal T3/T4/TSH) with medication
  • 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 (e.g., 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
  • For those undergoing rectal biopsies, a rectal condition, such as an active infection or inflammation of the colorectal area (e.g., an HSV-2 outbreak or inflamed hemorrhoids or colitis/diarrhea), internal hemorrhoids, or any other condition noted during screening rectal exam via anoscope or in medical history that in the opinion of the clinician represents a contraindication to mucosal sampling
  • For those undergoing vaginal and cervical biopsies, any condition noted during pelvic exam via speculum or in medical history that in the opinion of the clinician represents a contraindication to mucosal sampling
  • An active genital tract condition, such as an active infection or inflammation of the genital tract (e.g., genital sores or ulcers, penile or abnormal vaginal discharge, genital warts that are symptomatic or requiring treatment) or any other condition that in the opinion of the clinician represents a contraindication to mucosal sampling
  • Hysterectomy
  • Menopause
  Contacts and Locations
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): NCT02797171


Locations
United States, California
Bridge HIV CRS Recruiting
San Francisco, California, United States, 94143
Contact: Theresa M. Wagner, M.P.H.    415-437-7436    Theresa.Wagner@sfdph.org   
United States, Ohio
Case Clinical Research Site Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Baum, R.N.    216-844-2546    jb@clevelandactu.org   
United States, Pennsylvania
Penn Prevention CRS Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Debora Dunbar, M.S.N., C.R.N.P.    215-746-3713    ddunbar@mail.med.upenn.edu   
United States, Washington
Seattle Vaccine and Prevention CRS Recruiting
Seattle, Washington, United States, 98109-1024
Contact: David Berger, R.N.    206-667-2344    dberger@fhcrc.org   
South Africa
Groote Schuur HIV CRS Recruiting
Cape Town, Western Cape Province, South Africa, 7925
Contact: Christie Heiberg, B.Sc.    27-21-6503621    Christie.Heiberg@hiv-research.org.za   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Julie McElrath Seattle Vaccine Trials Unit
Study Chair: Linda-Gail Bekker Desmond Tutu HIV Centre
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02797171     History of Changes
Other Study ID Numbers: HVTN 116
20733 ( Registry Identifier: DAIDS-ES Registry Number )
First Submitted: June 7, 2016
First Posted: June 13, 2016
Last Update Posted: October 26, 2017
Last Verified: October 2017

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

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antiviral Agents
Anti-Infective Agents