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N-803 Combined With the Broadly Neutralizing Antibodies Plus or Minus haNK Cells for HIV

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04144335
Recruitment Status : Withdrawn (Contact issues)
First Posted : October 30, 2019
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
University of Minnesota

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.

Condition or disease Intervention/treatment Phase
Hiv HIV/AIDS HIV Infections AIDS AIDS and Infections Aids/Hiv Problem Biological: N-803 and bNAbs Biological: haNK™ Cells Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Group 1: N-803 and bNAbs Only
Group 1 will receive only N-803 and the bNAbs; they will not receive the haNK™ cells
Biological: N-803 and bNAbs
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.

Experimental: Group 2: N-803 and bNAbs with 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.
Biological: N-803 and bNAbs
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.

Biological: haNK™ Cells
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 Measures :
  1. Safety: Number of Adverse Events Grades 3, 4, 5 [ Time Frame: 27 weeks ]
    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 :
  1. Reduction of HIV Reservoir in PBMCs [ Time Frame: 27 weeks ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04144335


Locations
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United States, California
University of California
San Francisco, California, United States, 94143
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota Medical Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota
Investigators
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Principal Investigator: Timothy Schacker, MD Medical School, University of Minnesota

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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT04144335    
Other Study ID Numbers: STUDY00007810
First Posted: October 30, 2019    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Antibodies
Antibodies, Blocking
Immunologic Factors
Physiological Effects of Drugs