Single Center Study Of N-803 Stimulation On Expansion, Enrichment, Proliferation Of Natural Killer Cells Collected By Apheresis

Study Overview
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Brief Summary
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This is phase 1 single cohort study evaluating the effects of N-803 administration on mononuclear cells (MNC) collected from healthy donors undergoing a procedure called apheresis.

Detailed Description
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This phase 1, single cohort study will enroll up to 10 healthy subjects. All subjects will be pre-screened for eligibility. If the subject meets eligibility for study participation, informed consent will be obtained. Screening will include a history and physical, review of concomitant medications, assessment of NYHA functional status, assessment of ECOG performance status, clinical laboratory tests, pregnancy test (for women of child-bearing abilities), assessment of peripheral venous access, and a donor history questionnaire (DHQ). If subjects meet eligibility criteria, they will be asked to undergo two apheresis collections and donate their mononuclear cells (MNCs) for research purposes. Subjects will be scheduled for the first apheresis collection on study Day 1. Two total blood volume (TBV) will be processed during each apheresis collections, which is currently the collection centers standard practice. All subjects will receive N-803 at a fixed dose of 1 mg by subcutaneous (SC) injection 4 to 5 days prior to the second apheresis collection. The N-803 dose may be administered starting on study Day 8 but no later than study Day 24. The study day for N-803 administration will be determined based on the planned date of the second apheresis collection. The second apheresis collection should occur between study Day 12 and study Day 29. Two TBV will be processed during this collection. Subjects will be followed for collection of adverse events (AEs) from study Day 1 (first apheresis collection) through the end of study (EOS) visit. Subjects will be instructed to contact the study team in the event they experience AEs post N-803 administration (e.g., injection site reaction). In addition, AEs will be elicited from subjects during follow-up phone calls.

Official Title
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Single Center Study Evaluating The Effects Of N-803 Stimulation On The Expansion, Enrichment, And Proliferation Of Natural Killer Cells Collected By Apheresis

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: N-803


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old. Healthy donors must be free of acute or chronic medical conditions (e.g., hypertension, kidney disease, diabetes, autoimmune disease, cardiovascular disease). Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. Adequate organ function, evidenced by the following laboratory results: Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 Platelet count ≥ 100,000 cells/mm3 Hemoglobin ≥ 9.0 g/dL Total bilirubin ≤ 1.5 x upper limit of normal (ULN); unless the subject has documented Gilbert's syndrome Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 x ULN Serum creatinine ≤ 2.0 mg/dL or 177 μmol/L Adequate peripheral venous access. Must be able to be in the clinic for up to 6 hours on the day of collection. Must be able to sit or recline with limited movement for approximately 2-3 hours. Must agree to provide blood samples for clinical testing and immunological analysis. Eastern Cooperative Oncology Group (ECOG) performance status of 0. Exclusion Criteria: Received systemic antibiotics within 14 days prior to apheresis collection. New York Heart Association (NYHA) functional assessment score of > Class I. Any medical diagnosis that would prevent the donation of WBCs. History of or active human immunodeficiency virus (HIV). Active hepatitis B or hepatitis C. Have been advised by a medical provider not to donate blood. Women who are pregnant or breastfeeding. A negative serum pregnancy test in women of child-bearing potential is required at screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Up to 10 healthy subjects
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Subjects<br>Subjects will be scheduled for first apheresis collection on study Day 1. All subjects will receive N-803 at a fixed dose of 1 mg by subcutaneous (SC) injection 4 to 5 days prior to the second apheresis collection. The study day for N-803 administration will be determined based on the planned date of the second apheresis collection. | Drug: N-803<br>* fixed dose of 1 mg by subcutaneous (SC) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious adverse events (SAEs) and overall adverse events (AEs) coded in MedDRA | Incidence of SAEs and overall AEs coded in MedDRA | Study Day 1 through End of Study, assessed up to 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious adverse events (SAEs) and overall adverse events (AEs) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0) | Incidence of SAEs and overall AEs graded using the NCI CTCAE v5.0 | Study Day 1 through End of Study, assessed up to 45 days | 
| Evaluate and compare peripheral blood pre-apheresis and apheresis products collected without N-803 administration (unstimulated) and with N-803 administration (stimulated): - Percentage of NK cells | - Percentage of NK cells as measured by flow cytometry. | Study Day 1 through Study Day 24, assessed up to 24 days | 
| Evaluate and compare peripheral blood pre-apheresis and apheresis products collected without N-803 administration (unstimulated) and with N-803 administration (stimulated): - Immune profile | - Function and cell receptor profile of NK cells as measured by intracellular staining for cytokines, surface marker staining and assessments of cytotoxicity. | Study Day 1 through Study Day 24, assessed up to 24 days | 
| Evaluate and compare peripheral blood pre-apheresis and apheresis products collected without N-803 administration (unstimulated) and with N-803 administration (stimulated): - Serum cytokines | - Serum Cytokines | Study Day 1 through Study Day 24, assessed up to 24 days |