Back to resultsN-803 Combined With the Broadly Neutralizing Antibodies Plus or Minus haNK Cells for HIV
Primary Purpose
Hiv, HIV/AIDS, HIV Infections
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
N-803 and bNAbs
haNK™ Cells
Sponsored by
About this trial
This is an interventional treatment trial for Hiv
Eligibility Criteria
Inclusion Criteria:
- HIV-1 infection
- On continuous antiretroviral therapy for > 12 months without any interruptions of greater than 14 consecutive days in the last 12 months
- Screening plasma HIV RNA levels < 20 copies/mL on all available determinations in past 12 months (isolated single values ≥ 20 but < 200 copies/mL will be allowed if they were preceded and followed by viral load determinations < 20 copies/mL)
- Screening CD4+ T-cell count ≥ 400 cells/mm3
Exclusion Criteria:
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
- Active or recent malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months; minor surgical removal of localized skin cancers (squamous cell carcinoma, basal cell carcinoma) are not exclusionary
- Chronic liver disease defined as Class B and C on the Child-Pugh scale
- Active and poorly controlled atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 ACC/AHA guidelines, including a previous diagnosis of any of the following: (a) acute myocardial infarction, (b) acute coronary syndromes, (c) stable or unstable angina, (d) coronary or other arterial revascularization, (e) stroke, (f) transient ischemic attack (TIA), or (g) peripheral arterial disease grade IIa or greater
- History of AIDS-defining illness within the past 5 years
- History of potential immune-mediated medical conditions requiring concomitant treatment with immunomodulatory drugs, and/or exposure to any immunomodulatory drug in the 4 weeks prior to study enrollment
- Exposure to any experimental therapies within 90 days of study entry
Sites / Locations
- University of California
- Beth Israel Deaconess Medical Center
- University of Minnesota Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Group 1: N-803 and bNAbs Only
Group 2: N-803 and bNAbs with haNK™ Cells
Arm Description
Group 1 will receive only N-803 and the bNAbs; they will not receive the haNK™ cells
The protocol for Group 2 will be identical to the one followed by Group 1, except that they will receive haNK™ cells on the same day as each dose of N-803.
Outcomes
Primary Outcome Measures
Safety: Number of Adverse Events Grades 3, 4, 5
Number of serious adverse events (SAEs) graded 3 (severe pain; interferes with oral intake), 4 (life-threatening consequences; urgent intervention needed), and 5 (death) experienced in the haNK cell group compared to the group receiving no haNK cells. Lower number of SAEs indicated greater treatment safety.
Secondary Outcome Measures
Reduction of HIV Reservoir in PBMCs
HIV RNA in peripheral blood mononuclear cells (PBMCs) will be quantified using next gen sequencing. Percent reduction in HIV RNA reservoirs in these cells will be compared between groups. Greater percent reduction in viral reservoirs in haNK cell group indicates greater efficacy of haNK cell therapy compared to no haNK cell therapy.
Full Information
NCT ID
NCT04144335
First Posted
October 28, 2019
Last Updated
October 21, 2020
Sponsor
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT04144335
Brief Title
N-803 Combined With the Broadly Neutralizing Antibodies Plus or Minus haNK Cells for HIV
Official Title
A Phase 1B Study of N-803 Combined With the Broadly Neutralizing Antibodies VRC07-523LS and PGT121 Plus or Minus haNK Cells for Reduction of HIV Reservoirs
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Contact issues
Study Start Date
January 1, 2020 (Anticipated)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
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
To assess the safety of combination immune therapy in HIV-infected participants whose HIV is controlled with ART, by determining the incidence and severity of adverse events.
Detailed Description
This is a phase 1b study to examine the safety, tolerability and efficacy of the combination of 4 immunotherapies for treatment of HIV in participants with controlled HIV viremia and stable CD4 counts on antiretroviral therapy (ART).
The study will be conducted in two separate phases using two distinct to groups of participants where each group will have 10 individuals enrolled.
Treatment will consist of N-803, VRC07-523LS, PGT121, and haNK, with N-803 given for 3 cycles of 9 weeks/cycle. N-803 will be given every 3 weeks (3 doses/cycle), bNAbs will be given every 9 weeks, and haNK cells administered on the same day as each infusion of N-803. Total study duration will be 27 weeks.
Group 1 will receive only N-803 and the bNAbs; they will not receive the haNK™ cells. When 2 participants are enrolled and on active treatment for one month in Group 1, the Safety Monitoring Committee will review all data and if there are no safety concerns raised in the data recorded from administration of the interventions to those participants, Group 1 will continue. When Group 1 is complete, the SMC will again review all data before Group 2 can proceed with enrollment. The protocol for Group 2 will be identical to the one followed by Group 1, except that they will receive haNK™ cells at 2 × 109 cells/dose IV on the same day as each dose of N-803.
Optional tissue biopsies (lymph node and colonoscopy to collect gut-associated lymphoid tissue (GALT)) will occur at baseline and again 9 weeks after the last infusion of bNAbs. We aim to perform biopsies on least 8 out of 10 participants in each group.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hiv, HIV/AIDS, HIV Infections, AIDS, AIDS and Infections, Aids/Hiv Problem
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: N-803 and bNAbs Only
Arm Type
Active Comparator
Arm Description
Group 1 will receive only N-803 and the bNAbs; they will not receive the haNK™ cells
Arm Title
Group 2: N-803 and bNAbs with haNK™ Cells
Arm Type
Experimental
Arm Description
The protocol for Group 2 will be identical to the one followed by Group 1, except that they will receive haNK™ cells on the same day as each dose of N-803.
Intervention Type
Biological
Intervention Name(s)
N-803 and bNAbs
Intervention Description
Treatment will consist of N-803, VRC07-523LS, PGT121, and haNK, with N-803 given for 3 cycles of 9 weeks/cycle. N-803 will be given every 3 weeks (3 doses/cycle) and bNAbs will be given every 9 weeks.
Intervention Type
Biological
Intervention Name(s)
haNK™ Cells
Intervention Description
Treatment will consist of N-803, VRC07-523LS, PGT121, and haNK, with N-803 given for 3 cycles of 9 weeks/cycle. N-803 will be given every 3 weeks (3 doses/cycle), bNAbs will be given every 9 weeks, and haNK cells administered on the same day as each infusion of N-803.
Primary Outcome Measure Information:
Title
Safety: Number of Adverse Events Grades 3, 4, 5
Description
Number of serious adverse events (SAEs) graded 3 (severe pain; interferes with oral intake), 4 (life-threatening consequences; urgent intervention needed), and 5 (death) experienced in the haNK cell group compared to the group receiving no haNK cells. Lower number of SAEs indicated greater treatment safety.
Time Frame
27 weeks
Secondary Outcome Measure Information:
Title
Reduction of HIV Reservoir in PBMCs
Description
HIV RNA in peripheral blood mononuclear cells (PBMCs) will be quantified using next gen sequencing. Percent reduction in HIV RNA reservoirs in these cells will be compared between groups. Greater percent reduction in viral reservoirs in haNK cell group indicates greater efficacy of haNK cell therapy compared to no haNK cell therapy.
Time Frame
27 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HIV-1 infection
On continuous antiretroviral therapy for > 12 months without any interruptions of greater than 14 consecutive days in the last 12 months
Screening plasma HIV RNA levels < 20 copies/mL on all available determinations in past 12 months (isolated single values ≥ 20 but < 200 copies/mL will be allowed if they were preceded and followed by viral load determinations < 20 copies/mL)
Screening CD4+ T-cell count ≥ 400 cells/mm3
Exclusion Criteria:
Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
Active or recent malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months; minor surgical removal of localized skin cancers (squamous cell carcinoma, basal cell carcinoma) are not exclusionary
Chronic liver disease defined as Class B and C on the Child-Pugh scale
Active and poorly controlled atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 ACC/AHA guidelines, including a previous diagnosis of any of the following: (a) acute myocardial infarction, (b) acute coronary syndromes, (c) stable or unstable angina, (d) coronary or other arterial revascularization, (e) stroke, (f) transient ischemic attack (TIA), or (g) peripheral arterial disease grade IIa or greater
History of AIDS-defining illness within the past 5 years
History of potential immune-mediated medical conditions requiring concomitant treatment with immunomodulatory drugs, and/or exposure to any immunomodulatory drug in the 4 weeks prior to study enrollment
Exposure to any experimental therapies within 90 days of study entry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Schacker, MD
Organizational Affiliation
Medical School, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Minnesota Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
N-803 Combined With the Broadly Neutralizing Antibodies Plus or Minus haNK Cells for HIV
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