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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Recruitment Status : Withdrawn (Contact issues)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

Tracking Information
First Submitted Date  ICMJE October 28, 2019
First Posted Date  ICMJE October 30, 2019
Last Update Posted Date January 28, 2020
Estimated Study Start Date  ICMJE January 1, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04144335 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2019)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE N-803 Combined With the Broadly Neutralizing Antibodies Plus or Minus haNK Cells for HIV
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hiv
  • HIV/AIDS
  • HIV Infections
  • AIDS
  • AIDS and Infections
  • Aids/Hiv Problem
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
    Intervention: Biological: N-803 and bNAbs
  • 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.
    Interventions:
    • Biological: N-803 and bNAbs
    • Biological: haNK™ Cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: January 24, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2019)
20
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04144335
Other Study ID Numbers  ICMJE STUDY00007810
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Minnesota
Study Sponsor  ICMJE University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Timothy Schacker, MD Medical School, University of Minnesota
PRS Account University of Minnesota
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP