Back to resultsSafety, 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
Primary Purpose
HIV Infection
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
N-803 (IL-15 Superagonist)
VRC07-523LS
10-1074
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infection
Eligibility Criteria
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
Sites / Locations
- UCLA CARE Center CRS
- UCSD Antiviral Research Center CRS (Site ID: 701)Recruiting
- Ucsf Hiv/Aids CrsRecruiting
- Whitman-Walker Institute, Inc. CRS (Site ID: 31791)Recruiting
- Northwestern University CRSRecruiting
- Massachusetts General Hospital CRS (MGH CRS) (Site ID: 101)
- Washington University Therapeutics (WT) CRSRecruiting
- New Jersey Medical School Clinical Research Center CRS [Site ID: 31786]
- Columbia P&S CRS
- Weill Cornell Uptown CRS (Site ID: 7803)Recruiting
- Chapel Hill CRS (Site ID: 3201)
- Case Clinical Research SiteRecruiting
- Penn Therapeutics, CRS (Site ID: 6201)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A: N-803 only
Arm B: N-803 in combination with 10-1074 and VRC07-523LS
Arm Description
Participants will receive N-803 6 mcg/kg 1 week after Step 2 entry and then every 3 weeks for a total of eight doses.
Participants will receive N-803 in combination with 10-1074 and VRC07-523LS as follows: At Step 2 entry: VRC07-523LS 20 mg/kg 10-1074 30 mg/kg At Step 2, week 1: N-803 6 mcg/kg every 3 weeks for eight doses At Step 2, week 9: 10-1074 30 mg/kg
Outcomes
Primary Outcome Measures
Occurrence of a Grade ≥3 adverse event (AE) that is at least possibly related to N-803, as judged by the Clinical Management Committee (CMC)
Number of N-803 doses completed
Eight doses of N-803 are scheduled at the distinct time points listed in Time Frame. At each timepoint, dose completion status is recorded. Number of N-803 doses completed is the total number completed doses across all 8 timepoints.
Proportion of participants requiring dose reduction
Eight doses of N-803 are scheduled at distinct time points (Step 2 weeks 1, 4, 7, 10, 13, 16, 19 and 22). Proportion of participants requiring dose reduction is calculated as the number of participants who receive a reduced dose of N-803 at any of the 7 scheduled doses occurring after the first dose, divided by the total number of participants receiving N-803.
Proportion of participants with plasma HIV-1 RNA <200 copies/mL 8 weeks after interruption of ART
Secondary Outcome Measures
Occurrence of a Grade ≥2 AE without regard to relationship to study treatment
Occurrence of a Grade ≥2 AE that is at least possibly related to N-803, as judged by the CMC
Occurrence of a Grade ≥2 AE that is at least possibly related to VRC07-523LS or 10-1074
Cell-associated HIV-1 RNA
Measurement of HIV-1 reservoir (dQVOA)
Measurement of plasma viremia by HIV-1 single copy assay
Measurement of intact proviral DNA
Total HIV-1 DNA
Proportion of participants with plasma HIV-1 RNA <200 copies/mL at 4, 12 and 24 weeks after interruption of ART in Step 3
PK parameters: AUC0-τ of 10-1074
PK parameters: AUC0-τ of VRC07-523LS
Proportion of participants with antidrug antibodies
Presence of anti-N803, anti-10-1074, and anti-VRC07-523LS antibodies
Full Information
NCT ID
NCT04340596
First Posted
March 23, 2020
Last Updated
September 25, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Rockefeller University, ImmunityBio, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04340596
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 21, 2021 (Actual)
Primary Completion Date
October 31, 2025 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Rockefeller University, ImmunityBio, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
Detailed 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A: N-803 only
Arm Type
Experimental
Arm Description
Participants will receive N-803 6 mcg/kg 1 week after Step 2 entry and then every 3 weeks for a total of eight doses.
Arm Title
Arm B: N-803 in combination with 10-1074 and VRC07-523LS
Arm Type
Experimental
Arm Description
Participants will receive N-803 in combination with 10-1074 and VRC07-523LS as follows:
At Step 2 entry:
VRC07-523LS 20 mg/kg
10-1074 30 mg/kg
At Step 2, week 1: N-803 6 mcg/kg every 3 weeks for eight doses
At Step 2, week 9: 10-1074 30 mg/kg
Intervention Type
Biological
Intervention Name(s)
N-803 (IL-15 Superagonist)
Intervention Description
Administered by subcutaneous (SQ) injection
Intervention Type
Biological
Intervention Name(s)
VRC07-523LS
Intervention Description
Administered by intravenous (IV) infusion
Intervention Type
Biological
Intervention Name(s)
10-1074
Intervention Description
Administered by intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Occurrence of a Grade ≥3 adverse event (AE) that is at least possibly related to N-803, as judged by the Clinical Management Committee (CMC)
Time Frame
Step 2 week 1 to week 52
Title
Number of N-803 doses completed
Description
Eight doses of N-803 are scheduled at the distinct time points listed in Time Frame. At each timepoint, dose completion status is recorded. Number of N-803 doses completed is the total number completed doses across all 8 timepoints.
Time Frame
From step 2 week 1 to step 2 week 22
Title
Proportion of participants requiring dose reduction
Description
Eight doses of N-803 are scheduled at distinct time points (Step 2 weeks 1, 4, 7, 10, 13, 16, 19 and 22). Proportion of participants requiring dose reduction is calculated as the number of participants who receive a reduced dose of N-803 at any of the 7 scheduled doses occurring after the first dose, divided by the total number of participants receiving N-803.
Time Frame
From step 2 week 4 to step 2 week 22
Title
Proportion of participants with plasma HIV-1 RNA <200 copies/mL 8 weeks after interruption of ART
Time Frame
At step 3 week 8
Secondary Outcome Measure Information:
Title
Occurrence of a Grade ≥2 AE without regard to relationship to study treatment
Time Frame
Study entry to participant's last study visit, at approx. study week 100
Title
Occurrence of a Grade ≥2 AE that is at least possibly related to N-803, as judged by the CMC
Time Frame
Step 2 week 1 to week 52
Title
Occurrence of a Grade ≥2 AE that is at least possibly related to VRC07-523LS or 10-1074
Time Frame
Step 2 week 0 to week 52
Title
Cell-associated HIV-1 RNA
Time Frame
At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Title
Measurement of HIV-1 reservoir (dQVOA)
Time Frame
At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Title
Measurement of plasma viremia by HIV-1 single copy assay
Time Frame
At step 1 pre-entry evaluation and step 2 weeks 0, 1, 7, 13, 22 and 32
Title
Measurement of intact proviral DNA
Time Frame
At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Title
Total HIV-1 DNA
Time Frame
At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Title
Proportion of participants with plasma HIV-1 RNA <200 copies/mL at 4, 12 and 24 weeks after interruption of ART in Step 3
Time Frame
At step 3 weeks 4, 12, and 24
Title
PK parameters: AUC0-τ of 10-1074
Time Frame
At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46
Title
PK parameters: AUC0-τ of VRC07-523LS
Time Frame
At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46
Title
Proportion of participants with antidrug antibodies
Description
Presence of anti-N803, anti-10-1074, and anti-VRC07-523LS antibodies
Time Frame
At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Wilkin, MD, MPH
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Study Chair
Facility Information:
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90035
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aleen Khodabakhshian
Phone
310-557-2273
Ext
20891
Email
akhodabakhshian@mednet.ucla.edu
Facility Name
UCSD Antiviral Research Center CRS (Site ID: 701)
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Hendrickx, R.N.
Phone
619-543-6968
Email
smhendrickx@health.ucsd.edu
Facility Name
Ucsf Hiv/Aids Crs
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elvira Gomez
Phone
415-476-4082
Ext
106
Email
elvira.gomez@ucsf.edu
Facility Name
Whitman-Walker Institute, Inc. CRS (Site ID: 31791)
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20005
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Avery A Wimpelberg, B.A., CCRC
Phone
202-797-3589
Email
awimpelberg@whitman-walker.org
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Baiba Berzins, M.P.H.
Phone
312-695-5012
Email
Baiba@northwestern.edu
Facility Name
Massachusetts General Hospital CRS (MGH CRS) (Site ID: 101)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy Sbrolla, R.N., B.S.N., A.C.R.N.
Phone
1-617-7265598
Email
asbrolla@mgh.harvard.edu
Facility Name
Washington University Therapeutics (WT) CRS
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael K Klebert
Phone
314-747-1098
Email
mklebert@wustl.edu
Facility Name
New Jersey Medical School Clinical Research Center CRS [Site ID: 31786]
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christie L Costanza
Phone
973-972-9069
Email
costancl@njms.rutgers.edu
Facility Name
Columbia P&S CRS
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Palmer, PA-C
Phone
212-342-2958
Email
sp500@cumc.columbia.edu
Facility Name
Weill Cornell Uptown CRS (Site ID: 7803)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Fry, M.S.N., FNP
Phone
212-746-4166
Email
ref2007@med.cornell.edu
Facility Name
Chapel Hill CRS (Site ID: 3201)
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Becky Straub, B.S.N., M.P.H., R.N.
Phone
1-919-843-9975
Email
bstraub@med.unc.edu
Facility Name
Case Clinical Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jane Baum, R.N.
Phone
216-844-2546
Email
baum.jane@clevelandactu.org
Facility Name
Penn Therapeutics, CRS (Site ID: 6201)
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Baer, M.B., MBS
Phone
215-349-5023
Email
Baer2@pennmedicine.upenn.edu
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie results in the publication, after deidentification.
IPD Sharing Time Frame
Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
IPD Sharing Access Criteria
With whom?
Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.
For what types of analyses?
To achieve aims in the proposal approved by the AIDS Clinical Trials Group.
By what mechanism will data be made available?
Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.
Links:
URL
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables
Description
Related Info
URL
https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids
Description
Related Info
Learn more about this trial
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
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