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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/14/2021.

Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants

Clinicaltrials.gov identifier NCT03928821

Recruitment Status Active, not recruiting

First Posted April 26, 2019

Last update posted March 2, 2020

Study Description

Brief summary:

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-uninfected adults.

  • Condition or Disease:HIV Infections
  • Intervention/Treatment: Biological: PGT121
    Biological: PGDM1400
    Biological: 10-1074
    Biological: VRC07-523LS
  • Phase: Phase 1
Detailed Description

This study will evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-uninfected adults. Participants will initially be enrolled into one of three groups. At Day 0, Groups 1, 2, and 3 will receive dual combinations of mAbs administered sequentially via IV. Group 1 will receive a combination of PGT121 and VRC07-523LS, Group 2 will receive PGDM1400 and VRC07-523LS, and Group 3 will receive 10-1074 and VRC07-523LS. Study staff will review study data from Groups 1, 2, and 3 and determine if Group 4 may begin to enroll. Participants in Group 4 will receive PGDM1400, PGT121, and VRC07-523LS administered in sequence via IV on Day 0 and at Month 4. Study duration will be 12 months for participants in Groups 1, 2, and 3, and 16 months for participants in Group 4. Participants will attend several study visits, which may include physical examinations, blood and urine collection, HIV testing and pretest counseling, risk reduction counseling, and questionnaires.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 27 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Prevention
  • Official Title: A Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants
  • Actual Study Start Date: July 2019
  • Estimated Primary Completion Date: January 2021
  • Estimated Study Completion Date: January 2021
Arms and interventions
Arm Intervention/treatment
Experimental: Group 1: PGT121 + VRC07-523LS
Participants will receive PGT121 and VRC07-523LS administered sequentially in this order at Day 0.
Biological: PGT121
20 mg/kg administered intravenously

Biological: VRC07-523LS
20 mg/kg administered intravenously
Experimental: Group 4: PGDM1400 + PGT121 + VRC07-523LS
Participants will receive PGDM1400, PGT121, and VRC07-523LS administered sequentially in this order at Day 0 and Month 4.
Biological: PGT121
20 mg/kg administered intravenously

Biological: PGDM1400
20 mg/kg administered intravenously

Biological: VRC07-523LS
20 mg/kg administered intravenously
Experimental: Group 2: PGDM1400 + VRC07-523LS
Participants will receive PGDM1400 and VRC07-523LS administered sequentially in this order at Day 0.
Biological: PGDM1400
20 mg/kg administered intravenously

Biological: VRC07-523LS
20 mg/kg administered intravenously
Experimental: Group 3: 10-1074 + VRC07-523LS
Participants will receive 10-1074 and VRC07-523LS administered sequentially in this order at Day 0.
Biological: 10-1074
20 mg/kg administered intravenously

Biological: VRC07-523LS
20 mg/kg administered intravenously
Outcome Measures
  • Primary Outcome Measures: 1. Frequency of systemic Solicited AEs [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    Systemic symptoms to be assessed as Solicited AEs in this trial include increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, urticaria, non-exertional dyspnea, non-exertional tachycardia, generalized pruritus, facial flushing, and unexplained diaphoresis.
  • 2. Frequency of local Solicited adverse events (AEs) [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    Local symptoms to be assessed as Solicited AEs in this trial include pain and/or tenderness at the infusion site.
  • 3. Frequency of Unsolicited AEs [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    Unsolicited AEs will be summarized using MedDRA System Organ Class and preferred terms.
  • 4. Frequency of serious adverse events (SAEs) [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
  • 5. Number of participants who discontinue administration early [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
  • 6. Number of participants who terminate the study early [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
  • 7. Serum concentrations of PGT121 among participants who received all scheduled product administrations [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A quantitative immunoassay will be used to determine the concentration of each mAb.
  • 8. Serum concentrations of PGDM1400 among participants who received all scheduled product administrations [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A quantitative immunoassay will be used to determine the concentration of each mAb.
  • 9. Serum concentrations of 10-1074 among participants who received all scheduled product administrations [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A quantitative immunoassay will be used to determine the concentration of each mAb.
  • 10. Serum concentrations of VRC07-523LS among participants who received all scheduled product administrations [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A quantitative immunoassay will be used to determine the concentration of each mAb.
  • 11. Magnitude of serum neutralizing activity among participants who received all scheduled product administrations [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    Measured with mAb-specific Env-pseudotyped viruses in TZM-bl cells.
  • Secondary Outcome Measures: 1. Serum concentrations of PGT121 for all participants in all groups regardless of how many product administrations and how much product they received [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A quantitative immunoassay will be used to determine the concentration of each mAb.
  • 2. Serum concentrations of PGDM1400 for all participants in all groups regardless of how many product administrations and how much product they received [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A quantitative immunoassay will be used to determine the concentration of each mAb.
  • 3. Serum concentrations of 10-1074 for all participants in all groups regardless of how many product administrations and how much product they received [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A quantitative immunoassay will be used to determine the concentration of each mAb.
  • 4. Serum concentrations of VRC07-523LS for all participants in all groups regardless of how many product administrations and how much product they received [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A quantitative immunoassay will be used to determine the concentration of each mAb.
  • 5. Magnitude of serum neutralizing activity for all participants in all groups regardless of how many product administrations and how much product they received [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    Measured with Env pseudotyped viruses in TZM-bl cells
  • 6. Magnitude of neutralizing activity for all participants in all groups regardless of how many product administrations and how much product they received [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    Measured against a panel of Env pseudotyped reference viruses in TZM-bl cells
  • 7. Anti-drug antibody (ADA) titers for all participants in all groups regardless of how many product administrations and how much product they received [ Time Frame: Measured through participant's last study visit, which will be Month 12 or 16 depending on group ]
    A tiered testing approach will be used to identify and characterize ADAs that may arise.
Eligibility Criteria
  • Ages Eligible for Study: 18 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 low risk of HIV exposure through the last
required protocol clinic visit (see the protocol for more information)

Laboratory Inclusion Values

Hemogram/Complete Blood Count

- 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 feminizing 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 persons assigned female sex at birth).

- White blood cell count equal to 2,500 to 12,000 cells/mm^3

- White blood cell (WBC) differential either within institutional normal range or with
site clinician 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; creatinine less than or equal to institutional upper limit of
normal

Virology

- Negative HIV-1 and -2 blood test: US volunteers must have a negative Food and Drug
Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent
microparticle immunoassay (CMIA).

- 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 product administration. 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 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 one of the
following methods:

- Condoms (male or female) with or without a spermicide,

- Diaphragm or cervical cap with spermicide,

- Intrauterine device (IUD),

- Hormonal contraception,

- Tubal ligation,

- Any other contraceptive method approved by the HVTN 130/HPTN 089 Protocol Safety
Review Team (PSRT)

- Successful vasectomy in any partner assigned male sex at birth (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 reached menopause (no menses
for 1 year) or having undergone hysterectomy or bilateral oophorectomy;

- Or be sexually abstinent.

- 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 130/HPTN 089 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 130/HPTN 089 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 130/HPTN 089 PSRT will determine
eligibility on a case-by-case basis.

- Previous receipt of humanized or human mAbs, whether licensed or investigational; the
HVTN 130/HPTN 089 PSRT will determine eligibility on a case-by-case basis.

- Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-523LS, PGT121,
PGDM1400, or 10-1074

Immune System

- Immunosuppressive medications received within 30 days before first study product
administration (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled
corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatological
condition; or [4] a single course of oral/parenteral prednisone or equivalent at doses
less than 20 mg/day and length of therapy less than 14 days.)

- Serious adverse reactions to VRC07-523LS, PGT121, PGDM1400, or 10-1074 formulation
components (acetate, sucrose, polysorbate 80, histidine, and sorbitol; see the
protocol for more information), including history of anaphylaxis and related symptoms
such as hives, respiratory difficulty, angioedema, and/or abdominal pain

- Immunoglobulin received within 90 days before first study product administration,
unless eligibility for earlier enrollment is determined by the HVTN 130/HPTN 089 PSRT
(for mAb see criterion above)

- 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 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 infusions, or blood draws, including inability
to establish venous or sub-cutaneous 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 skin condition (eg, tattoos) that, in the
judgment of the investigator, would interfere with, or serve as a contraindication to,
protocol adherence, assessment of safety, 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, 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 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 exclusionary: 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 clinician (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

Contacts and Locations
Contacts
Locations

United States, Massachusetts
Fenway Health (FH) CRS
Boston

United States, New York
Harlem Prevention Center CRS
New York

United States, New York
Columbia P&S CRS
New York

United States, Tennessee
Vanderbilt Vaccine (VV) CRS
Nashville

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: Magdalena Sobieszczyk Columbia University

Study Chair: Sharon Mannheimer Columbia University

More Information
  • Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
  • ClinicalTrials.gov Identifier: NCT03928821 History of Changes
  • Other Study ID Numbers: HVTN 130/HPTN 089, 38531
  • First Posted: April 26, 2019 Key Record Dates
  • Last Update Posted: March 2, 2020
  • Last Verified: February 2020
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: HIV Infections