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HIV InfectionsPhase 1NCT03205917

A Clinical Trial of PGDM1400 and PGT121 and VRC07-523LS Monoclonal Antibodies in HIV-infected and HIV-uninfected Adults

A Phase 1 study of HIV Infections, run by International AIDS Vaccine Initiative at 1 site 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 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGDM1400 and PGT121 and VRC07-523LS mAbs 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 Infections
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
29 participants
Where
1 siteUnited States
Study dates
23 Oct 2017to 20 Apr 2020
Phase
Phase 1
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

Groups 1 and 2 Inclusion Criteria:

  • HIV-uninfected males or females age 18-50 years old
  • Willing to maintain low risk behavior for HIV infection

Groups 1 and 2 Exclusion Criteria:

  • Confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities

Group 3 Inclusion Criteria:

  • HIV-infected males or females age 18-65 years old
  • Not on antiretroviral therapy with HIV-1 RNA plasma level between 1,000 and 100,000 copies/ml, CD4 cell count ≥ 300 cells/uL

Group 3 Exclusion Criteria:

  • Significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase 1 Randomized Placebo-controlled Clinical Trial of the Safety, Pharmacokinetics and Antiviral Activity of PGDM1400 and PGT121 and VRC07-523LS Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults

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

Read the detailed description

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGDM1400, PGT121 and VRC07-523LS mAbs for HIV prevention and therapy. PGDM1400, PGT121 and VRC07-523LS mAbs are recombinant human IgG1 monoclonal antibodies that target V1V2 (PGDM1400), a V3 glycan-dependent epitope (PGT121) and the CD4 binding site (VRC07-523LS) epitope region of the HIV envelope protein. PGT121, PGDM1400 and VRC07-523LS mAb 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.

Conditions
HIV Infections
Being tested
PGDM1400/Placebo (3mg/kg IV), PGDM1400/Placebo (10mg/kg IV), PGDM1400/Placebo (30mg/kg IV), PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV), PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)
Medical subject headings
HIV Infections

What participants receive

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

  • PGDM1400/Placebo (3mg/kg IV)Biological

    3/1 (6/2 if DLT)

  • PGDM1400/Placebo (10mg/kg IV)Biological

    3/1 (6/2 if DLT)

  • PGDM1400/Placebo (30mg/kg IV)Biological

    3/1 (6/2 if DLT)

  • PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV)Biological

    3/1 (6/2 if DLT)

  • PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)Biological

    3/1 (6/2 if DLT);

  • PGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV)Biological

    3/1 (6/2 if DLT)

  • PGDM1400 + PGT121 + VRC07-523LS (20mg/kg + 20mg/kg + 20 mg/kg IV)Biological

    3 (max 9)

  • PGDM1400 + PGT121 (MTD IV)Biological

    3 (max 9)

Study groups in NCT03205917
Study groupRoleWhat they receive
Group 1A HIV-UninfectedExperimentalPGDM1400 low dose
Receives: Biological: PGDM1400/Placebo (3mg/kg IV)
Group 1B HIV-UninfectedExperimentalPGDM1400 mid dose
Receives: Biological: PGDM1400/Placebo (10mg/kg IV)
Group 1C HIV-UninfectedExperimentalPGDM1400 high dose
Receives: Biological: PGDM1400/Placebo (30mg/kg IV)
Group 2A HIV-UninfectedExperimentalPGDM1400 + PGT121 low dose
Receives: Biological: PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV)
Group 2B HIV-UninfectedExperimentalPGDM1400 + PGT121 mid dose
Receives: Biological: PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)
Group 2C HIV-UninfectedExperimentalPGDM1400 + PGT121 high dose
Receives: Biological: PGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV)
Group 3A HIV-infected off ARTExperimentalPGDM1400 + PGT121 + VRC07-523LS at 20mg/kg; HIV+ without ART
Receives: Biological: PGDM1400 + PGT121 + VRC07-523LS (20mg/kg + 20mg/kg + 20 mg/kg IV)
Group 3B HIV-infected off ARTExperimentalPGDM1400 + PGT121 at high dose; HIV + without ART
Receives: Biological: PGDM1400 + PGT121 (MTD IV)

What is being measured

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

  1. Safety and tolerability

    1. Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) for 3 days following IV infusion of PGDM1400 mAb alone, and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb
    2. Proportion of participants with adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, during the first 56 days following IV infusion of PGDM1400 mAb alone and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb, that are moderate or greater, and/or related to PGDM1400 mAb or PGT121 mAb or VRC07-523LS mAb
    3. Proportion of participants with SAEs throughout the study period following IV infusion of PGDM1400 mAb alone and a combination of PGDM1400 mAb and PGT121 mAb, and a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb, that are related to PGDM1400 mAb or PGT121 mAb or VRC07-523LS mAb

    Measured: 6 Months post infusion

  2. Elimination half-life (t1/2)

    Elimination half-life following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults

    Measured: 6 Months post infusion

  3. Clearance (CL/F)

    Clearance following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults.

    Measured: 6 months post infusion

  4. Volume of distribution (Vz/F)

    Volume of distribution following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults

    Measured: 6 months post infusion

  5. Area under the concentration decay curve (AUC)

    AUC following IV infusion of PGDM1400 mAb alone or a combination of PGDM1400 mAb and PGT121 mAb in HIV-uninfected and HIV-infected adults; or a combination of PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb in HIV-infected adults

    Measured: 6 months post infusion

  6. Impact of viral load and/or ART

    Impact of viral load and/or ART on PGDM1400 mAb and PGT121 mAb and VRC07-523LS mAb disposition

    Measured: 6 months post infusion

  7. Antiviral activity of PGDM1400 in combination with PGT121 or PGDM1400 in combination with PGT121 and VRC07-523LS mAbs

    Antiviral activity following IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb, in viremic HIV-infected adults not on ART:

    Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)

    Measured: 6 Months post infusion

Secondary outcomes (4)

  1. Serum antibody titers against bNAbs

    Serum anti-PGDM1400 antibody titers, Serum anti-PGT121 antibody titers and Serum anti-VRC07-523LS antibody titers

    Measured: 6 Months post infusion

  2. CD4+ T cell count

    Determine if IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb, has any impact on CD4+ T cell counts in HIV-infected adults. Change in CD4+ T cell count compared to baseline as measured by single platform flow cytometry

    Measured: 6 Months post infusion

  3. HIV genotyping of circulating virus

    Compare plasma virus genotype activity before and after IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb to determine if PGDM1400 mAb and PGT121 mAb and/or PGT121VRC07-523LS mAb induced viral escape mutations have developed in viremic HIV-infected adults not on ART

    Genotypic analysis: Development of sequence variations in epitopes known to result in reduced PGDM1400 mAb and/or PGT121 mAb and/or VRC07-523LS mAb neutralization susceptibility or known to cause resistance to antiretroviral drugs

    Measured: 6 Months post infusion

  4. HIV phenotyping of circulating virus

    Compare plasma virus phenotypic activity before and after IV infusion of PGDM1400 mAb in combination with PGT121 mAb, or PGDM1400 mAb in combination with PGT121 mAb and VRC07-523LS mAb to determine if PGDM1400 mAb and PGT121 mAb and/or PGT121VRC07-523LS mAb induced viral escape mutations have developed in viremic HIV-infected adults not on ART. Phenotypic analysis: Changes in viral susceptibility to PGDM1400 mAb and/or PGT121 mAb and/or VRC07-523LS mAb neutralization

    Phenotypic analysis: Changes in viral susceptibility to PGDM1400 mAb and/or PGT121 mAb and/or VRC07-523LS mAb neutralization.

    Measured: 6 months post infusion

Timeline

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

  1. First posted2 Jul 2017
  2. Study start23 Oct 2017
  3. Primary completion20 Apr 2020
  4. Study completion20 Apr 2020

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
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03205917
Sponsor's protocol ID
IAVI T002
Status last verified
Sep 2020
First submitted
12 May 2017
Last updated
14 Sep 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Julg B, Stephenson KE, Wagh K, Tan SC, Zash R, Walsh S, Ansel J, Kanjilal D, Nkolola J, Walker-Sperling VEK, Ophel J, Yanosick K, Borducchi EN, Maxfield L, Abbink P, Peter L, Yates NL, Wesley MS, Hassell T, Gelderblom HC, deCamp A, Mayer BT, Sato A, Gerber MW, Giorgi EE, Gama L, Koup RA, Mascola JR, Monczor A, Lupo S, Rolle CP, Arduino R, DeJesus E, Tomaras GD, Seaman MS, Korber B, Barouch DH. Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial. Nat Med. 2022 Jun;28(6):1288-1296. doi: 10.1038/s41591-022-01815-1. Epub 2022 May 12.

    PubMed 35551291

Questions about this trial

What is this clinical trial studying?

A Phase 1 study of HIV Infections, run by International AIDS Vaccine Initiative at 1 site 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?

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 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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.

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 (time frame: 6 Months post 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 NCT03205917, 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 14 Sep 2020.

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