NCT03205917

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at P25-P50 for phase_1 hiv-infections

Timeline
Completed

Started Oct 2017

Typical duration for phase_1 hiv-infections

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 12, 2017

Completed
2 months until next milestone

First Posted

Study publicly available on registry

July 2, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

October 23, 2017

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 20, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 20, 2020

Completed
Last Updated

September 14, 2020

Status Verified

September 1, 2020

Enrollment Period

2.5 years

First QC Date

May 12, 2017

Last Update Submit

September 11, 2020

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (7)

  • 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

    6 Months post infusion

  • 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

    6 Months post infusion

  • 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.

    6 months post infusion

  • 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

    6 months post infusion

  • 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

    6 months post infusion

  • 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

    6 months post infusion

  • 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)

    6 Months post infusion

Secondary Outcomes (4)

  • Serum antibody titers against bNAbs

    6 Months post infusion

  • CD4+ T cell count

    6 Months post infusion

  • HIV genotyping of circulating virus

    6 Months post infusion

  • HIV phenotyping of circulating virus

    6 months post infusion

Study Arms (8)

Group 1A HIV-Uninfected

EXPERIMENTAL

PGDM1400 low dose

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

Group 1B HIV-Uninfected

EXPERIMENTAL

PGDM1400 mid dose

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

Group 1C HIV-Uninfected

EXPERIMENTAL

PGDM1400 high dose

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

Group 2A HIV-Uninfected

EXPERIMENTAL

PGDM1400 + PGT121 low dose

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

Group 2B HIV-Uninfected

EXPERIMENTAL

PGDM1400 + PGT121 mid dose

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

Group 2C HIV-Uninfected

EXPERIMENTAL

PGDM1400 + PGT121 high dose

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

Group 3A HIV-infected off ART

EXPERIMENTAL

PGDM1400 + PGT121 + VRC07-523LS at 20mg/kg; HIV+ without ART

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

Group 3B HIV-infected off ART

EXPERIMENTAL

PGDM1400 + PGT121 at high dose; HIV + without ART

Biological: PGDM1400 + PGT121 (MTD IV)

Interventions

PGDM1400/Placebo (3mg/kg IV)BIOLOGICAL

3/1 (6/2 if DLT)

Group 1A HIV-Uninfected
PGDM1400/Placebo (10mg/kg IV)BIOLOGICAL

3/1 (6/2 if DLT)

Group 1B HIV-Uninfected
PGDM1400/Placebo (30mg/kg IV)BIOLOGICAL

3/1 (6/2 if DLT)

Group 1C HIV-Uninfected
PGDM1400 + PGT121/Placebo (3mg/kg + 3mg/kg IV)BIOLOGICAL

3/1 (6/2 if DLT)

Group 2A HIV-Uninfected
PGDM1400 + PGT121/Placebo (10mg/kg + 10mg/kg IV)BIOLOGICAL

3/1 (6/2 if DLT);

Group 2B HIV-Uninfected
PGDM1400 + PGT121/Placebo (30mg/kg + 30mg/kg IV)BIOLOGICAL

3/1 (6/2 if DLT)

Group 2C HIV-Uninfected
PGDM1400 + PGT121 + VRC07-523LS (20mg/kg + 20mg/kg + 20 mg/kg IV)BIOLOGICAL

3 (max 9)

Group 3A HIV-infected off ART
PGDM1400 + PGT121 (MTD IV)BIOLOGICAL

3 (max 9)

Group 3B HIV-infected off ART

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities
  • 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
  • Significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

  • 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.

    PMID: 35551291DERIVED

Related Links

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Boris Juelg, MD, PhD

    Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research, Ragon Institute of MGH, MIT and Harvard

    PRINCIPAL INVESTIGATOR

  • Kathryn Stephenson, MD, MPH

    Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 12, 2017

First Posted

July 2, 2017

Study Start

October 23, 2017

Primary Completion

April 20, 2020

Study Completion

April 20, 2020

Last Updated

September 14, 2020

Record last verified: 2020-09

Locations

US(1)