Delving into the Latest Updates on VRC-01-LS with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

VRC-HIVMAB-080-00-AB, VRC 01LS, VRC01LS

Target

HIV envelope protein gp120

Mechanism

HIV envelope protein gp120 inhibitors

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

HIV Infections

Inactive Indication-

Originator Organization

National Institute of Allergy & Infectious Diseases

Active Organization

Xencor, Inc.

National Institutes of Health

Inactive Organization

National Institute of Allergy & Infectious Diseases

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 177375L

Sequence Code 4701666H

Background:
The human body uses antibodies as one way to help fight infection. VRC01LS and VRC07-523LS are antibodies directed against the HIV virus. Researchers want to see if they are safe and well tolerated. In Part A of the study, the researchers studied VRC01LS. Part A of the study was completed in 2017. In Part B, the researchers studied VRC07-523LS. Depending on which antibody received, researchers studied the amount of VRC01LS or VRC07-523LS in the body and how it changes over time. They evaluated the effect of antibodies on CD4+ (Cluster of Differentiation 4) lymphocyte count and HIV viral load, and checked to see if people who get VRC01LS or VRC07-523LS develop an immune response to it.
Objective:
To see if VRC01LS and VRC07-523LS are safe and well tolerated.
Eligibility:
Adults ages 18-70 who are HIV infected but otherwise healthy.
Design:
Participants received the study drug one time by IV infusion. A needle guided a thin tube into a vein. The study drug mixed with salt water was dripped into the vein over about 30 minutes.
Participants were monitored for 30 minutes after the infusion.
Blood samples were taken at the following times:
Once before the infusion
5 times in the 4 hours after the infusion
1 time 24 hours after infusion. Some participants may have had 3 optional blood draws in the time period between 4 and 24 hours.
For 3 days after the infusion, participants recorded their temperature and reactogenicity symptoms in a diary.
There were a total of 23 study visits over 48 weeks. Ten visits were in the first 4 weeks. At all visits, participants answered health questions and gave blood samples.

Start Date24 Apr 2017

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+1]

NCT02797171 / CompletedPhase 1IIT

A Phase 1 Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Anti-Viral Activity of VRC-HIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB (VRC01LS) in the Serum and Mucosa of Healthy, HIV-Uninfected Adult Participants

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.

Start Date01 Mar 2017

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with VRC-01-LS

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100 Translational Medicine associated with VRC-01-LS

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100 Patents (Medical) associated with VRC-01-LS

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8

Literatures (Medical) associated with VRC-01-LS

05 Jul 2023·Science translational medicineQ1 · MEDICINE

Broadly neutralizing antibody treatment maintained HIV suppression in children with favorable reservoir characteristics in Botswana

Q1 · MEDICINE

Article

Author: Sakoi, Maureen ; Giguel, Francoise ; Cooper, Marlene ; Moyo, Sikhulile ; Pretorius Holme, Molly ; Lichterfeld, Mathias ; Yu, Xu ; Makhema, Joseph ; Maphorisa, Comfort ; Gao, Ce ; Batlang, Oganne ; Ackerman, Margaret E. ; Capparelli, Edmund V. ; Kuritzkes, Daniel R. ; Maswabi, Kenneth ; Caskey, Marina ; Reeves, Jacqueline D. ; Ajibola, Gbolahan ; Shapiro, Roger L. ; McDermott, Adrian ; Reeves, Michael A. ; Yin, Dwight E. ; Nelson, Bryan S. ; Mohammed, Terence ; Bennett, Kara ; Hu, Zixin ; Gama, Lucio ; Lockman, Shahin ; Niesar, Aischa ; Jean-Philippe, Patrick ; Powis, Kathleen M. ; Hughes, Michael

Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have immunotherapeutic effects against HIV-1 reservoirs. We conducted a prospective clinical trial with two HIV-1 bNAbs (VRC01LS and 10-1074) in children (n= 25) who had previously initiated small-molecule ART treatment before 7 days of age and who continued treatment for at least 96 weeks. Both bNAbs were dosed intravenously every 4 weeks, overlapping with ART for at least 8 weeks and then continued for up to 24 weeks or until detectable viremia of HIV-1 RNA rose above 400 copies per milliliter in the absence of ART. Eleven (44%) children maintained HIV-1 RNA below 400 copies per milliliter through 24 weeks of bNAb-only treatment; 14 (56%) had detectable viremia above 400 copies per milliliter at a median of 4 weeks. Archived HIV-1 provirus susceptible to 10-1074, lower birth HIV-1 DNA reservoir in peripheral blood mononuclear cells, sustained viral suppression throughout early life, and combined negative qualitative HIV-1 DNA polymerase chain reaction and negative HIV-1 serology at entry were associated with maintaining suppression on bNAbs alone. This proof-of-concept study suggests that bNAbs may represent a promising treatment modality for infants and children living with HIV-1. Future studies using newer bNAb combinations with greater breadth and potency are warranted.

01 Oct 2022·Journal of acquired immune deficiency syndromes (1999)

Safety and Pharmacokinetics of Intravenous 10-1074 and VRC01LS in Young Children

Article

Author: Mosher, Shad ; Taylor, Alison ; Hughes, Michael D. ; Gama, Lucio ; Caskey, Marina ; Maswabi, Kenneth ; Ajibola, Gbolahan ; Mcdermott, Adrian ; O’Connell, Sarah ; Mohammed, Terence ; Moyo, Sikhulile ; Tomaras, Georgia D. ; Lockman, Shahin ; Kuritzkes, Daniel R. ; Bennett, Kara ; Lichterfeld, Mathias ; Holme, Molly P. ; Makhema, Joseph ; Narpala, Sandeep ; Shapiro, Roger L. ; Capparelli, Edmund V. ; Jean-Philippe, Patrick ; Powis, Kathleen M. ; Seaton, Kelly E. ; Maphorisa, Comfort

Background::

Broadly neutralizing monoclonal antibodies (bNAbs) suppress HIV-1 RNA and may deplete residual viral reservoirs. We evaluated the safety and pharmacokinetics (PK) of dual intravenous VRC01LS and 10-1074 in very early-treated children with HIV-1 on suppressive antiretroviral treatment (ART).

Setting::

Botswana.

Methods::

Children with HIV-1 (median age 3.1 years) on ART from <7 days old were enrolled. In phase A, 6 children received 10-1074 (30 mg/kg at day 0, 28, and 56) and 6 children received VRC01LS (30 mg/kg at day 0, 10 mg/kg at days 28 and 56) by intravenous infusion. In phase B, 6 children received the 2 bNAbs combined (with higher VRC01LS maintenance dose, 15 mg/kg) every 4 weeks for 32 weeks with PK evaluations over 8 weeks. Population PK models were developed to predict steady-state concentrations.

Results::

BNAb infusions were well tolerated. There were no infusion reactions nor any bNAb-related grade 3 or 4 events. The median (range) first dose Cmax and trough (day 28) combined from both phases were 1405 (876–1999) μg/mL and 133 (84–319) μg/mL for 10-1074 and 776 (559–846) μg/mL and 230 (158–294) μg/mL for VRC01LS. No large differences in bNAb clearances were observed when given in combination. The estimated VRC01LS half-life was shorter than in adults. Predicted steady-state troughs [median (90% prediction interval)] were 261 (95–565) and 266 (191–366) μg/mL for 10-1074 and VRC01LS, respectively, when given in combination.

Conclusions::

10-1074 and VRC01LS were safe and well-tolerated among children receiving ART. Troughs exceeded minimal targets with every 4-week administration of 10-1074 at 30 mg/kg and VRC01LS at 15 mg/kg.

01 Dec 2021·The Journal of infectious diseases

Safety, Tolerability, and Pharmacokinetics of a Long-Acting Broadly Neutralizing Human Immunodeficiency Virus Type 1 (HIV-1) Monoclonal Antibody VRC01LS in HIV-1–Exposed Newborn Infants

Article

Author: Anderson, Thuy ; Graham, Barney S ; Capparelli, Edmund V ; Eysallenne, Zulma ; Leon, Dayana ; Rogo, Tanya ; Flach, Britta ; Rossouw, Lindie ; Maraqa, Nizar ; Cavallo, Martha ; Rossouw, Magdel ; Rathore, Mobeen H ; Navarro, Kacey ; Agwu, Allison ; Cunningham, Coleen K ; Baig, Mahboobullah M ; Purswani, Murli ; Louw, Jeanne ; Persaud, Deborah ; Vhembo, Tichaona ; Smith, Betsy ; Robinson, Lisa-Gaye ; Morgan, Patricia ; McMullen-Jackson, Chivon ; Purdue, Lynette ; Paul, Mary E ; Puga, Ana M ; McDermott, Adrian B ; Pontifes, Mariam ; Matibe, Petronella ; Maldonado, Alexandrea ; Buschur, Shelley ; Glenny, Carrie ; Mujuru, Hilda ; Mahmoudi, Saniyyah ; Taylor, Alison ; Golden, W Christopher ; Mhembere, Tsungai Patience ; Collinson-Streng, Aleisha ; Lin, Bob C ; Mascola, John R ; McFarland, Elizabeth J ; Dunn, Jennifer ; Muresan, Petronella ; Perlowski, Charlotte ; Harding, Paul A ; Theron, Gerhard ; Hazra, Rohan ; Sung, Joyce

Abstract:

Background:

Perinatal human immunodeficiency virus type 1 (HIV-1) continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs).

Methods:

An extended half-life bNAb, VRC01LS, was administered subcutaneously at 80 mg/dose after birth to HIV-1–exposed, nonbreastfed (cohort 1, n = 10) and breastfed (cohort 2, n = 11) infants. Cohort 2 received a second dose (100 mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort.

Results:

Local reactions (all grade ≤2) occurred in 67% and 20% after dose 1 and dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administered subcutaneously achieved a mean (standard deviation) plasma level of 222.3 (71.6) µg/mL by 24 hours and 44.0 (11.6) µg/mL at week 12, prior to dose 2. The preestablished target of ≥50 µg/mL was attained in 95% and 32% at weeks 8 and 12, respectively. The terminal half-life was 37–41 days. VRC01LS level after 1 dose was significantly greater (P <.002) than after a VRC01 dose (20 mg/kg). No infants acquired HIV-1.

Conclusions:

VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.

100 Deals associated with VRC-01-LS

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 2	BW	National Institute of Allergy & Infectious Diseases	17 Jun 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02256631 (CTgov)	Phase 1	HIV Infections	83	VRC01 (Dose Group 1)	qaqdnxirar(mvfjlwwkqm) = dihqwrntpu usycfuebby (rruhgfewkb, ajfxebzcix - zxducggsvu) View more	-	23 Aug 2021
				VRC01 (Dose Group 2)	qaqdnxirar(mvfjlwwkqm) = qmbcyvkssy usycfuebby (rruhgfewkb, eofksyxbtg - mjtmvzxbht) View more
NCT02256631 (Pubmed)	Phase 1	HIV Infections	83	VRC01LS 80mg	igqpbovwkw(lxxvaxaokq) = pkbynhntxy opchpomcgj (ywroyverqj, + 71.6)	-	02 May 2021
				VRC01LS 100mg	igqpbovwkw(lxxvaxaokq) = eddnbzyfzj opchpomcgj (ywroyverqj, + 11.6)
NCT02840474 (CTgov)	Phase 1	HIV Infections	16	VRC-HIVMAB080-00-AB (Part A: VRC01LS (40 mg/kg))	nfgsmnupnd(cibsnlhusg) = phejottdjp sowuwuwvxk (rbdwrdeprn, owpyucusea - eqexixyonv) View more	-	23 Feb 2021
				VRC-HIVMAB075-00-AB (Part B: VRC07-523LS (40 mg/kg))	nfgsmnupnd(cibsnlhusg) = kzspybqnmx sowuwuwvxk (rbdwrdeprn, xrjbvawgdz - sboxxpislg) View more
VRC 607/ACTG 5378 (IAS2019)	Not Applicable	HIV Infections	16	VRC01LS	xszhxdrdyg(ylkzkvbpfr) = zsrrvygcbq bgztsythti (nmperyrwma )	-	01 Jan 2019
				VRC07-523LS	xszhxdrdyg(ylkzkvbpfr) = bfckqipnfx bgztsythti (nmperyrwma )
NCT02599896 (Pubmed \| PLoS Med) Manual	Phase 1	HIV Infections	37	VRC01LS	sfvagpzhas(hlxzkivwsr) = gimdbpcmsk vtmneheoky (zcrlcvbgft ) View more	Positive	24 Jan 2018