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HIV/AIDSPhase 1/2NCT03721510

A Phase 1/2a Study of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults

A Phase 1/2 study testing PGT121 + VRC07-523LS and PGT121 + VRC07-523LS + PGDM1400 in people with HIV/AIDS, run by International AIDS Vaccine Initiative at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1/2a open label study to evaluate the safety, tolerability, pharmacokinetics and anti-viral activity of PGT121, VRC07-523LS and PGDM1400 for HIV prevention and therapy. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
HIV/AIDS
What is being tested?
PGT121 + VRC07-523LS and PGT121 + VRC07-523LS + PGDM1400
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
3 sitesUnited States
Study dates
3 Dec 2018to 2 May 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • Any clinically significant acute or chronic medical condition, other than HIV infection, that is considered progressive or in the opinion of the investigator makes the volunteer unsuitable for participation in the study.
  • Any clinically relevant abnormality on history or examination including history of immunodeficiency (other then HIV infection) or autoimmune disease; use of systemic corticosteroids, immunosuppressive, anticancer, or other medications considered significant by the investigator within the previous 6 months. The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least 6 weeks prior to enrollment in this study.
  • If born female, pregnant, lactating or planning a pregnancy during the period of screening through completion of the study.
  • In the past 6 months a history of alcohol or substance use, including marijuana, judged by the Investigator to potentially interfere with volunteer study compliance.
  • Bleeding disorder that was diagnosed by a physician. Note: A volunteer who states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience, is eligible.
  • History of a splenectomy.
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  • Receipt of live attenuated vaccine within the previous 30 days or planned receipt within 30 days after administration of investigational product; or receipt of other vaccine within the previous 14 days or planned receipt within 14 days after infusion with investigational product (exception is live attenuated influenza vaccine within 14 days).
  • Receipt of blood transfusion or blood-derived products within the previous 3 months.
  • Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study. Note: receipt of placebo in a clinical trial in the previous 3 months will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval.
  • Prior receipt of an investigational HIV vaccine candidate, monoclonal antibody or polyclonal immunoglobulin. Note: receipt of placebo in a previous HIV vaccine or monoclonal antibody trial will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval.
  • History of severe local or systemic reactogenicity to injections or IV infusion (e.g., anaphylaxis, respiratory difficulties, angioedema).
  • Psychiatric condition that compromises safety of the volunteer and 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.
  • If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.
  • Seizure disorder: a volunteer who has had a seizure in the last 3 years is excluded.
  • Body mass index ≥ 35 or ≤ 18.5.
  • Infectious disease: chronic hepatitis B infection (HbsAg), current hepatitis C infection (HCV Ab positive and HCV RNA positive) or interferon-alfa treatment for chronic hepatitis C infection in the past year, chlamydia, gonorrhea, or active syphilis.
  • A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
  • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic, antiviral or antifungal therapy within 30 days prior to enrollment.
  • Any of the following abnormal laboratory parameters listed below:
  • Hematology
  • Hemoglobin < 10.5 g/dL in females; hemoglobin <11.0 g/dL in males
  • Absolute Neutrophil Count (ANC): ≤ 1000/mm3
  • Platelets: < 100,000 mm3 or ≥ 550,000/mm3 Chemistry
  • AST ≥ 1.5 x ULN
  • ALT ≥ 1.5 x ULN
  • Total bilirubin ≥ 1.1 x ULN
  • Alkaline phosphatase ≥ 1.5 x ULN
  • Albumin ≤ 3.0 g/dL (equivalent to ≤ 30 g/L)
  • Estimated Glomerular filtration rate (GFR) < 60 ml/min according to the Cockcroft Gault formula for creatinine clearance
  • Male: (140 - age in years) x (wt in kg) = CLcr (ml/min) / 72 x (serum creatinine in mg/dL)
  • Female: (140 - age in years) x (wt in kg) x 0.85 = CLcr (mL/min) / 72 x (serum creatinine in mg/dL)
  • Urinalysis: Any of the following abnormal findings if consistent with clinically significant disease:
  • Protein = 2+ or more
  • Blood = 2+ or more (not due to menses)
  • Specific exclusion criteria for HIV-uninfected volunteers (Group 1):
  • 1. Confirmed HIV-1 infection

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Center for Virology and Vaccine Research/ Clinical Trials Unit/ BIDMC

    Boston, Massachusetts, 02215

  • Houston AIDS Research Team (HART)

    Houston, Texas, 77030

  • Orlando Immunology Center

    Orlando, Florida, 32803

Other trials in United States

About this study

Official title: A Phase 1/2a Open Label Study of the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults

This is a Phase 1/2a open label study to evaluate the safety, tolerability, pharmacokinetics and anti-viral activity of PGT121, VRC07-523LS and PGDM1400 for HIV prevention and therapy.

Read the detailed description

This is a Phase 1/2a open label study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of PGT121, VRC07-523LS and PGDM1400 antibodies for HIV prevention and therapy. PGT121, VRC07-523LS and PGDM1400 are recombinant human IgG1 monoclonal antibodies that target a V3 glycan-dependent epitope region of the HIV envelope protein and the CD4 binding site (CD4bs) of the HIV envelope protein. PGT121, VRC07-523LS and PGDM1400 mAbs were chosen for this study because of their potency, their ability to neutralize a wide array of cross-clade HIV viruses in a complementary pattern, and their proven antiviral activity in animal studies, e.g., their capacity to robustly prevent and treat simian-human immunodeficiency virus (SHIV) in rhesus monkeys.

The potency and breadth of PGT121, VRC07-523LS and PGDM1400 raise the possibility that monoclonal antibodies may be effective for HIV prophylaxis at low doses and against global viruses. Neutralization sensitivity profiles are complementary; and the combination of these mAbs with unique epitope specificities will provide experience assessing the potential additive, synergistic, or antagonistic properties of two bNAbs given sequentially.

Conditions
HIV/AIDS
Being tested
PGT121 + VRC07-523LS, PGT121 + VRC07-523LS + PGDM1400
Keywords
HIV, AIDS, Monoclonal antibodies, Neutralizing antibodies, Analytical treatment interruption
Medical subject headings
Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PGT121 + VRC07-523LSBiological

    PGT121 + VRC07-523LS, dose 30 mg/kg each, given intravenously

  • PGT121 + VRC07-523LS + PGDM1400Biological

    PGT121 + VRC07-523LS + PGDM1400, dose 20 mg/kg each, given intravenously

Study groups in NCT03721510
Study groupRoleWhat they receive
Group 1AActive comparatorHIV-uninfected volunteers receiving one IV infusion
Receives: Biological: PGT121 + VRC07-523LS
Group 1BActive comparatorHIV-uninfected volunteers receiving one IV infusion
Receives: Biological: PGT121 + VRC07-523LS + PGDM1400
Group 2Active comparatorHIV-infected volunteers on ART receiving three or six IV infusions
Receives: Biological: PGT121 + VRC07-523LS + PGDM1400

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Tolerability - Proportion of volunteers with moderate or greater reactogenicity

    Proportion of volunteers with moderate or greater reactogenicity (i.e., solicited adverse events) for 3 days following each IV infusion of PGT121, VRC07-523LS and PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)

    Measured: 3 days post infusion for each infusion

  2. Safety and Tolerability - Proportion of volunteers with adverse events (AEs)

    Proportion of volunteers with adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, during the 56 days following IV infusion of PGT121, VRC07-523LS and PGDM1400 that are moderate or greater, and/or considered related to PGT121 and/or VRC07-523LS and/or PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)

    Measured: 56 days

  3. Safety and Tolerability - Proportion of volunteers with serious adverse events (SAEs)

    Proportion of volunteers with serious adverse events (SAEs) throughout the study period following IV infusion(s) of PGT121, VRC07-523LS and PGDM1400 that are considered related to PGT121 and/or VRC07-523LS and/or PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)

    Measured: Up to 44 weeks

  4. Pharmacokinetics - Elimination half-life (t1/2)

    Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults:

    • Elimination half-life (t1/2)

    Measured: Up to 44 weeks

  5. Pharmacokinetics - Clearance (CL/F)

    Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults:

    • Clearance (CL/F)

    Measured: Up to 44 weeks

  6. Pharmacokinetics - Volume of distribution (Vz/F)

    Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults:

    • Volume of distribution (Vz/F)

    Measured: Up to 44 weeks

  7. Pharmacokinetics - Area under the concentration decay curve (AUC)

    Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults:

    • Area under the concentration decay curve (AUC)

    Measured: Up to 44 weeks

Secondary outcomes (10)

  1. Antiviral Activity - Proportion of volunteers who meet ART re-initiation criteria

    Proportion of volunteers who meet ART re-initiation criteria (defined as plasma HIV-1 RNA ≥ 1000 copies/ml and/or CD4 count < 300 cells/μl) on two consecutive measurements following ART interruption in Group 2

    Measured: Up to 44 weeks

  2. Antiviral Activity - Time to meeting ART re-initiation criteria

    Time to meeting ART re-initiation criteria (plasma HIV-1 RNA level ≥ 1000 copies/ml, CD4+ T cell count < 300 cells/ μl in two consecutive measurements) following ART interruption in Group 2

    Measured: Up to 44 weeks

  3. mAb serum levels at the time of viral rebound in Group 2

    Serum levels of PGT121 at time of viral rebound

    Measured: Up to 44 weeks

  4. mAb serum levels at the time of viral rebound in Group 2

    Serum levels of VRC07-523LS at time of viral rebound

    Measured: Up to 44 weeks

  5. mAb serum levels at the time of viral rebound in Group 2

    Serum levels of PGDM1400 at time of viral rebound

    Measured: Up to 44 weeks

  6. CD4+ T cell count

    Change in CD4+ T cell count and frequency compared to baseline as measured by single platform flow cytometry in HIV-infected adults following IV infusion of PGT121, VRC07-523LS and PGDM1400.

    Measured: Up to 44 weeks

  7. Effects of PGT121, VRC07-523LS and PGDM1400 on viral escape mutations in rebound viruses

    Phylogenetic comparison of viruses grown from PBMCs collected from volunteers while on ART to rebound viruses collected after ART interruption (Group 2)

    Measured: Up to 44 weeks

  8. Anti-PGT121 antibodies

    Serum anti-PGT121 antibody titers

    Measured: Up to 44 weeks

  9. Anti-VRC07-523LS antibodies

    Serum anti-VRC07-523LS antibody titers

    Measured: Up to 44 weeks

  10. Anti-PGDM1400 antibodies

    Serum anti-PGDM1400 antibody titers

    Measured: Up to 44 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2018
  2. Study start3 Dec 2018
  3. Primary completion25 Oct 2021
  4. Study completion2 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03721510
Sponsor's protocol ID
IAVI T003
Status last verified
May 2022
First submitted
16 Mar 2018
Last updated
10 May 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Julg B, Walker-Sperling VEK, Wagh K, Aid M, Stephenson KE, Zash R, Liu J, Nkolola JP, Hoyt A, Castro M, Serebryannyy L, Yanosick K, Speidel T, Borducchi EN, Murzda T, Maxfield L, Arduino R, McDermott AB, Gama L, Giorgi EE, Koup RA, Seaman MS, Rolle CP, DeJesus E, Li W, Korber B, Barouch DH. Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial. Nat Med. 2024 Dec;30(12):3534-3543. doi: 10.1038/s41591-024-03247-5. Epub 2024 Sep 12.

    PubMed 39266747

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PGT121 + VRC07-523LS and PGT121 + VRC07-523LS + PGDM1400 in people with HIV/AIDS, run by International AIDS Vaccine Initiative at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability - Proportion of volunteers with moderate or greater reactogenicity (time frame: 3 days post infusion for each infusion). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03721510, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2022.

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