A Phase I Clinical Trial of the Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption

  • STATUS
    Recruiting
  • End date
    Nov 30, 2024
  • participants needed
    46
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 11 October 2022
dolutegravir
lamivudine
HIV Vaccine
hiv-1 rna measurement

Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Description

This study will evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Participants will be screened for eligibility and undergo leukapheresis, and a subset will also undergo optional rectal biopsy and/or lymph node fine needle aspirations (FNAs) (Step 1).

After pre-entry and determination of eligibility in Step 1, participants will be randomized before Step 2 entry to either the N-803 only arm (Arm A) or the N-803 with combination bNAbs arm (Arm B):

  • Arm A will receive a dose of N-803, 6 mcg/kg, subcutaneously 1 week after Step 2 entry and then every 3 weeks for a total of eight doses (during the first 22 weeks).
  • Arm B will receive the following (during the first 22 weeks):
  • Combination bNAb at Step 2 entry with VRC07-523LS dosed at 20 mg/kg and 10-1074 dosed at 30 mg/kg, intravenously;
  • A dose of N-803, 6 mcg/kg, subcutaneously 1 week after Step 2 entry and then every 3 weeks for a total of eight doses;
  • A second dose of 10-1074 at week 9 of Step 2 dosed at 30 mg/kg, intravenously

After completing randomized treatment (Step 2), participants will interrupt antiretroviral therapy (ART) (Step 3) and will be followed closely to monitor for indications for reinitiation of ART (Step 4).

After Step 2 entry, most participants will be followed for approximately 100 weeks across the remaining three study steps (i.e., Steps 2, 3, and 4).

Step 1 will last up to 90 days, Step 2 will last approximately 52 weeks (study intervention), Step 3 will last up to 24 weeks (ATI), and Step 4 will last 24 weeks (ART restart).

Details
Condition HIV Infection
Treatment 10-1074, VRC07-523LS, N-803 (IL-15 Superagonist)
Clinical Study IdentifierNCT04340596
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on11 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

HIV-1 infection
On ART for at least 96 weeks prior to randomization
On ART regimen containing an integrase inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIs) or dolutegravir/lamivudine for at least 6 weeks prior to randomization
CD4 cell count >450 cells/mm^3 within 90 days prior to randomization
CD4 cell count nadir ≥200 cells/mm^3
Plasma HIV-1 RNA levels of <50 copies/mL for at least 96 weeks prior to randomization
Select laboratory results within 90 days of randomization
IC90 to 10-1074 of ≤1.5 mcg/mL, 10-1074 maximum percent inhibition (MPI) ≥98%, and IC80 to VRC07-523LS of ≤1 mcg/mL on the Monogram PhenoSense assay
QTcF interval ≤440 msec within 90 days prior to randomization
For cisgender women and transgender men of reproductive potential, negative urine or serum pregnancy test within 30 days prior to randomization
Cisgender women and transgender men of reproductive potential must agree to use two methods of contraception, if participating in sexual activity that could lead to pregnancy
Cisgender men and transgender women participants engaging in sexual activity that could lead to pregnancy and who are of reproductive potential must agree to use a barrier method of contraception
Willingness to abstain from sexual intercourse or use a barrier method of contraception consistently
Willingness to participate in an ATI
Weight >50 kg and <115 kg
Completion of pre-entry leukapheresis

Exclusion Criteria

History of AIDS-defining illness, with the exception of recurrent pneumonia
History of or current clinical cardiovascular disease
Current clinically significant acute or chronic medical condition
History of HIV-associated neurocognitive disease
History of an HIV-associated malignancy
ART initiated during acute HIV infection
Current receipt of ART other than NRTI and integrase inhibitor
Resistance to one or more drugs in two or more ARV drug classes
Receipt of any therapeutic HIV vaccine or monoclonal antibody therapy (anti-HIV or otherwise) at any time in the past
History of prior immunoglobulin (IgG) therapy
History of use of any immunomodulatory medications within 6 months prior to randomization
Participation in another clinical study of an investigational product currently or within past 12 weeks
Breastfeeding or pregnancy
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note