Carcinoma, Lymphoma
Conditions
Keywords
Pharmacokinetics of lL-15, Cytokine Therapy, Effects of rhlL-15 on T-cells and NK cells, Immunotherapy
Brief summary
Background: \- People with cancer can have a weak immune system as a result of the cancer itself, or from prior treatments. Still, treatments that stimulate the immune system have been shown to be effective against a number of different cancers. Recombinant human interleukin-15 (rhIL-15) is a drug that is designed to boost the immune system. Researchers are interested in seeing if rhIL-15 can strengthen the immune system's response against cancer. The drug will be given through a vein without a break for 10 days (240 hours). Objectives: * To see rhIL-15 given as a continuous infusion over 10 days can be used to treat advanced cancer * Identify the side effects associated with this treatment. Eligibility: \- Individuals at least 18 years of age with advanced cancer for which there are no effective treatments. Design: * Participants screening procedures will include a physical exam and medical history, laboratory (blood) tests and x-rays (Imaging studies) to determine suitability for the protocol. * Appropriate participants with easily accessible tumor deposits may also be asked to have one pretreatment and one post (cycle 1) treatment tumor biopsy. * Eligible participants will be admitted to the hospital for the rhIL-15 treatment and will spend about 12 days in the hospital. * Participants will receive one 10 day infusion each cycle (about every 42 days) for as long as there are no serious side effects and the disease does not progress. * Participants will continue treatment as long as imaging studies show that the tumor continues to shrink or for two additional cycles after it has disappeared from the x-rays to make that the cancer is completely gone. * Participants who stop treatment for side effects or because their tumor did not shrink or stopped responding to the treatment will continue to have follow-up visits to monitor the outcome of the rhIL-15 treatment until there is evidence their cancer has progress or they begin another treatment.
Detailed description
BACKGROUND: * Interleukin-15 (IL-15) is a stimulatory cytokine with a number of desirable immunotherapeutic features, and clinical trials evaluating recombinant human interleukin-15 (rhIL-15) are underway. * In contrast to IL-2, IL-15 treatment does not stimulate activation-induced cell death of T-cells; potentially inhibits immunosuppressive cluster of differentiation 4 (CD4) + Interleukin-2 receptor alpha chain (CD25) + T regulatory cells, contributes to the proliferation, differentiation and activation of CD8+ T-cells and NK-cells and the maintenance of long-term cluster of differentiation 8 (CD8) + memory T-cells. * IL-15 is active in a number of syngeneic mouse preclinical tumor models, and vaccinia-based constructs expressing IL-15 induced long-lasting, high-avidity cytotoxic CD8+ T-lymphocyte response that appears to be more effective than similar IL-2 expressing vaccines. * Pharmacology/toxicology (pharm/tox) experiments in non-human primate (NHP) rhesus macaques and preliminary results from the first-in-human phase I trial examining rhIL-15 given as an intravenous (IV) bolus (IVB) for 12 consecutive days indicate significant stimulation and expansion of NK-cells and CD8+ T-cells. * rhIL-15 given as an IVB at 1 mcg/kg dose level appears to be well tolerated despite the presence of some common cytokine-related side effects indicating that 0.1 mcg/kg/day is an appropriate initial dose level for a phase I safety trial of continuous intravenous infusion (CIV) of rhIL-15. * Comparison of the pharmacokinetic and immunologic assessments from the IVB phase I trial with the data from both sets of NHP pharm/tox experiments suggest that continuous intravenous (CIV) of rhIL-15 may have greater potential for stimulating an anticancer cellular immune response with a more manageable safety profile. OBJECTIVES: Primary Objective: \- Determine the safety, toxicity profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of rhIL-15 administered as a CIV for 10 consecutive days (240 hours) in subjects with metastatic unresectable cancers for which curative or palliative measures either do not exist or are not associated with a survival advantage. ELIGIBILITY CRITERIA: * Patients greater than or equal to18 years-old, Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than or equal to 1, with pathologically confirmed metastatic unresectable cancers for which curative or palliative measures either do not exist or are not associated with a survival advantage. * Patients with measurable or evaluable disease, normal organ and bone marrow function. DESIGN: * This is a single-institution, open-label, non-randomized 3 + 3 design phase I dose escalation study. * Groups of 3 to 6 subjects will receive CIV rhIL-15 at doses of 0.1, 0.25, 0.5 1, 2, 4, 6 and 8 mcg/kg/day for 10 days provided that DLT has not been observed. * After assessments of the 10-day dosing cohorts have been completed, new groups of 3 to 6 subjects will receive CIV rhIL-15 at doses of 3, 4 and 5 mcg/kg/day for 5 days provided that a DLT has not been observed. * Patients with evidence of response and the absence of significant toxicities will be eligible for repeat cycles of treatment. * Samples for correlative studies will be obtained prior to treatment and at specific times points during and after treatment to assess pharmacokinetics of rhIL-15, the effect of rhIL-15 on immune cell subset populations and pro-inflammatory cytokine levels in the peripheral blood and for the development of neutralizing anti-rhIL-15 antibodies.
Interventions
BIOLOGICALrh IL-15 (10 DAYS)
Continuous infusion of recombinant human Interleukin-15 (rh IL-15) intravenous (IV) for first 10 days of each cycle
BIOLOGICALrh IL-15 (5 DAYS)
Continuous infusion of recombinant human Interleukin-15 (rh IL-15) for first 5 days of each cycle
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA * Age greater than or equal to 18 years. * Patients must have histologically confirmed (by the National Cancer Institute (NCI) Pathology Department) solid tumor malignancy or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are associated with minimal patient survival benefit (as defined the Metabolism Branch physicians or if the patient refuses standard of care treatment). Enrollment of patients with tumors that can be safely biopsied is encouraged. * Patients must have evaluable or measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan. * Patients must have recovered to \< grade 1 Common Terminology Criteria for Adverse Events (CTCAE)v4 from toxicity of prior chemotherapy or biologic therapy and must not have had prior chemotherapy or biologic therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C, 8 weeks for 7-hydroxystaurosporine (UCN-01). * Patients must be at least 1 month since any prior radiation or major surgery. * Patients on bisphosphonates for any cancer or on hormone therapy for prostate cancer will not need to discontinue this therapy to be eligible. However, patients with prostate cancer will need to have metastatic prostate cancer that has progressed despite hormonal therapy. Castrate testosterone levels occur within hours after castration and within 2 to 3 weeks of a luteinizing hormone-releasing hormone agonist. The current standard is to continue androgen suppression despite progressive disease. * Diffusing capacity for carbon monoxide (DLCO)/alveolar volume (VA) and forced expiratory volume (FEV)-1.0 \> 60% of predicted on pulmonary function tests. * Serum creatinine of less than or equal to 1.5 X the upper limit of normal. * Aspartate aminotransferase (AST) and alanine aminotransferase (AST) \< 2.5 x the upper limit of normal. * Absolute neutrophil count greater than or equal to 1,500/mm(3) and platelets greater than or equal to 100,000/mm(3). * Karnofsky performance status greater than or equal to 70% or Eastern Cooperative Oncology Group (ECOG) less than or equal to 1 * Subjects with inactive central nervous system (CNS) metastasis are eligible. Inactive CNS metastasis is defined as: no signs of cerebral edema after successful definitive treatment of brain metastases (surgical resection, whole brain irradiation, stereotactic radiation therapy, or a combination of these) with stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan at least 1 month after completion of treatment.
Exclusion criteria
* Patients who have received any systemic corticosteroid therapy within 3 weeks prior to the start of therapy with the exception of physiological replacement doses of cortisone acetate or equivalent. * Patients who have received any cytotoxic therapy, immunotherapy, antitumor vaccines, monoclonal antibodies or major surgery in the 4 weeks prior to the start of the study. * Life expectancy of less than 3 months. * Patients with more than 30% replacement of hepatic parenchyma by tumor or any history of drug related hepatic encephalopathy. * History of complex ventricular or supraventricular arrhythmias * Documented human immunodeficiency virus (HIV), active bacterial infections, active or chronic hepatitis B, or hepatitis C infection. * A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antigen (HBsAb) positive and hepatitis B core antibody (HBcAb) negative), or a fully resolved acute hepatitis B infection is not an exclusion criterion. * A positive hepatitis C serology is an exclusion criterion. * Concurrent anticancer therapy (including other investigational agents), with the exception of hormone therapy for prostate cancer. * Active central nervous system (CNS) metastases (inactive CNS metastases are defined). * History of severe asthma or presently on chronic inhaled corticosteroid medications (patients with a history of mild asthma controlled with inhaled bronchodilators are eligible). * History of autoimmune disease, with the exception of an autoimmune event associated with prior ipilimumab (anti-cluster of differentiation 152 (CTLA-4) therapy that has been completely resolved for more than 4 weeks. * Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding (men and women of childbearing potential must use an effective method of birth control or abstinence during treatment and for 4 months after completion of treatment). * Cognitive impairment, history of medical or psychiatric disease, other uncontrolled intercurrent illness, active substance abuse, or social circumstances, which in the view of the Principal Investigator (PI), would preclude safe treatment or the ability to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | After one cycle (one cycle is either 42 or 21 days) | A DLT is Grade 2 diarrhea lasting more than 24 hours or any grade 3 or 4 toxicity, if deemed possibly, probable or definitely related to the study drug by the principal investigator during the first cycle of treatment; and/or Grade 5 death related to adverse event. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4. Grade 3 is severe, and Grade 4 is life-threatening. |
| Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 10 Day Dosing | After one cycle (one cycle is 42 days for 10-day dosing) | The MTD is the dose level at which less than one-third of patients (0/3 or 0-1/6 participants) treated at that dose experience a dose-limiting toxicity (DLT), with the next higher dose level demonstrating a one-third or greater number of participants (≥ 2/3 or ≥ 2/6 participants) having DLT. A DLT is Grade 2 diarrhea lasting more than 24 hours or any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4. Grade 3 is severe, and Grade 4 is life-threatening. |
| Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 5 Day Dosing | After one cycle (one cycle is 21 days for 5-day dosing) | The MTD is the dose level at which less than one-third of patients (0/3 or 0-1/6 participants) treated at that dose experience a dose-limiting toxicity (DLT), with the next higher dose level demonstrating a one-third or greater number of participants (≥ 2/3 or ≥ 2/6 participants) having DLT. A DLT is Grade 2 diarrhea lasting more than 24 hours or any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4. Grade 3 is severe, and Grade 4 is life-threatening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15) | Prior to 1st dose, at 10 minutes after 1st dose, once daily on days 7-10 at completion of treatment, at 10 and 30 minutes after completion of treatment and at 1, 2, 4, and approximately 24 hours after completion of treatment. | The maximum observed analyte concentration in serum was reported. |
| Concentration of Drug in Plasma at Steady State (Css) | Days 7 through 10 | Concentration of drug in plasma at steady state (Css). |
| Inflammatory Cytokines | Pre, 0.16, 1, 2, 4, 8, 12, and 24 hours on Day 1. Days 2, 7, 8, 9, and 10. 0, 0.16, 0.32, 1, 2, 4, and 12 hours on Day 11. And 24 hours on Day 12. | Serum samples was obtained from participants and inflammatory cytokine analyses was performed by flow cytometry to determine levels of Interleukin - 1, Interferon γ, Interleukin-6 and Tumor Necrosis Factor ἁ. |
| Area Under the Curve (AUClast) | Prior to 1st dose, at 10 minutes after 1st dose, once daily on days 7-10 at completion of treatment, at 10 and 30 minutes after completion of treatment and at 1, 2, 4, and approximately 24 hours after completion of treatment. | AUClast is from dosing to the time of the last measured concentration \>/= lower limit of quantitation (LLOQ)(Clast) of that dosing period. |
| Clinical Response Rate | Both cycles 1 and 2 (each cycle is 42 days) for the 10 day treatment, up to 84 days. And clinical responses for the 5-day treatment cohorts (21 day cycle length) were assessed after cycles 2, 4, 6, 8 and so on treatment cycles. | Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Time to Progression (TTP) | From the date of protocol consent until date of progressive disease is documented, up to 263 days | TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | Date treatment consent signed to date off study, approximately 18 months (m)/27 days(d), 3 m, 9 m/13d, 15 m/20d, 28 m/17d, 1 m/23d, 15 m/8d, 4 m/5d, and 6 m/30d for levels 1-9 respectively. | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
Countries
United States
Participant flow
Pre-assignment details
No participants were enrolled in the dose expansion phase of the study.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation Level 1 - 0.1 mcg/kg/Day x 10 Days Level 1 - 0.1 mcg/kg/day x 10 Days | 4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days Level 2 - 0.25 mcg/kg/day x 10 Days | 3 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days Level 3 - 0.5 mcg/kg/day x 10 Days | 3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days Level 4 - 1 mcg/kg/day x 10 Days | 6 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days Level 5 - 2 mcg/kg/day x 10 Days | 9 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days Level 6 - 4 mcg/kg/day x 10 Days | 2 |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days Level 7 - 3 mcg/kg/day x 5 Days | 4 |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days Level 8 - 4 mcg/kg/day x 5 Days | 3 |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days Level 9 - 5 mcg/kg/day x 5 Days | 4 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Switched to alternative treatment | 0 | 1 | 2 | 1 | 2 | 0 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Dose Escalation Level 1 - 0.1 mcg/kg/Day x 10 Days | Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Total | Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 5 Participants | 0 Participants | 14 Participants | 2 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 24 Participants | 1 Participants | 3 Participants |
| Age, Continuous | 66.63 years STANDARD_DEVIATION 5.11 | 61.15 years STANDARD_DEVIATION 7.42 | 60.9 years STANDARD_DEVIATION 5.42 | 60.05 years STANDARD_DEVIATION 10.92 | 62.75 years STANDARD_DEVIATION 2.33 | 56.58 years STANDARD_DEVIATION 12.89 | 55.05 years STANDARD_DEVIATION 5.82 | 58.48 years STANDARD_DEVIATION 9.8 | 55.83 years STANDARD_DEVIATION 18.4 | 51.97 years STANDARD_DEVIATION 7.26 |
| Diagnosis Adenoid Cystic | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Diagnosis Adrenal | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Diagnosis Cholangiocarcinoma | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Diagnosis Colorectal cancer | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 7 Participants | 0 Participants | 0 Participants |
| Diagnosis Endometrial | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants |
| Diagnosis Esophageal | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Diagnosis Gastric neuro-ectodermal | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Diagnosis Gastrointestinal Stromal Tumor | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Diagnosis Head and Neck cancer | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants |
| Diagnosis Metastatic Melanoma | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants |
| Diagnosis Non-Small Cell Lung cancer (NSCLC) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Diagnosis Pancreatic cancer | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants |
| Diagnosis Prostate | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Diagnosis Renal Cell carcinoma | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 2 Participants |
| Diagnosis Sarcoma | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 0 Participants | 0 Participants |
| Diagnosis Small bowel | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 9 Participants | 6 Participants | 34 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants |
| Performance Status - Eastern Cooperative Oncology Group (ECOG) 0 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Performance Status - Eastern Cooperative Oncology Group (ECOG) 1 | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 9 Participants | 6 Participants | 38 Participants | 3 Participants | 3 Participants |
| Prior Therapy Checkpoint Inhibitors | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Therapy Chemotherapy | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 4 Participants | 5 Participants | 28 Participants | 1 Participants | 3 Participants |
| Prior Therapy Hormonal Therapy | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 0 Participants |
| Prior Therapy Immunotherapy | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 14 Participants | 0 Participants | 2 Participants |
| Prior Therapy Molecular Therapy | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Therapy Radiation Therapy | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 18 Participants | 2 Participants | 3 Participants |
| Prior Therapy Surgery | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 5 Participants | 26 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 5 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 2 Participants | 6 Participants | 4 Participants | 29 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 4 participants | 4 participants | 3 participants | 4 participants | 2 participants | 9 participants | 6 participants | 38 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 7 Participants | 2 Participants | 21 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 17 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 3 | 1 / 6 | 0 / 9 | 1 / 2 | 0 / 4 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 3 / 3 | 6 / 6 | 9 / 9 | 2 / 2 | 4 / 4 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 2 / 4 | 1 / 3 | 1 / 3 | 3 / 6 | 2 / 9 | 2 / 2 | 0 / 4 | 1 / 3 | 2 / 4 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 10 Day Dosing
The MTD is the dose level at which less than one-third of patients (0/3 or 0-1/6 participants) treated at that dose experience a dose-limiting toxicity (DLT), with the next higher dose level demonstrating a one-third or greater number of participants (≥ 2/3 or ≥ 2/6 participants) having DLT. A DLT is Grade 2 diarrhea lasting more than 24 hours or any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4. Grade 3 is severe, and Grade 4 is life-threatening.
Time frame: After one cycle (one cycle is 42 days for 10-day dosing)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 10 Day Dosing | 2 mcg/kg/day |
Primary
Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 5 Day Dosing
The MTD is the dose level at which less than one-third of patients (0/3 or 0-1/6 participants) treated at that dose experience a dose-limiting toxicity (DLT), with the next higher dose level demonstrating a one-third or greater number of participants (≥ 2/3 or ≥ 2/6 participants) having DLT. A DLT is Grade 2 diarrhea lasting more than 24 hours or any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4. Grade 3 is severe, and Grade 4 is life-threatening.
Time frame: After one cycle (one cycle is 21 days for 5-day dosing)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 5 Day Dosing | NA mcg/kg/day |
Primary
Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug
A DLT is Grade 2 diarrhea lasting more than 24 hours or any grade 3 or 4 toxicity, if deemed possibly, probable or definitely related to the study drug by the principal investigator during the first cycle of treatment; and/or Grade 5 death related to adverse event. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4. Grade 3 is severe, and Grade 4 is life-threatening.
Time frame: After one cycle (one cycle is either 42 or 21 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Participants | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 2 Participants |
| All Participants | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 0 Participants |
| All Participants | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 2 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 0 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 0 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 0 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 0 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 0 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 0 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 0 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 1 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 0 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 0 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 0 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 0 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 1 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 1 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 0 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 0 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 0 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 0 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 0 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 0 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 0 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 4 | 0 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 3 | 0 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug | Grade 5 | 0 Participants |
Secondary
Area Under the Curve (AUClast)
AUClast is from dosing to the time of the last measured concentration \>/= lower limit of quantitation (LLOQ)(Clast) of that dosing period.
Time frame: Prior to 1st dose, at 10 minutes after 1st dose, once daily on days 7-10 at completion of treatment, at 10 and 30 minutes after completion of treatment and at 1, 2, 4, and approximately 24 hours after completion of treatment.
Population: 3/4 participants in dose level 1, and 2/3 participants in dose level 2 were not evaluable for this outcome measure. AUClast was only performed for the 10 day dosing cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Area Under the Curve (AUClast) | 7756 pg/mL | — |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Area Under the Curve (AUClast) | 10907 pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Area Under the Curve (AUClast) | 20798 pg/mL | Geometric Coefficient of Variation 8667 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Area Under the Curve (AUClast) | 187453 pg/mL | Geometric Coefficient of Variation 206143 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Area Under the Curve (AUClast) | 321747 pg/mL | Geometric Coefficient of Variation 300686 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Area Under the Curve (AUClast) | 262651 pg/mL | Geometric Coefficient of Variation 77613 |
Secondary
Clinical Response Rate
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Both cycles 1 and 2 (each cycle is 42 days) for the 10 day treatment, up to 84 days. And clinical responses for the 5-day treatment cohorts (21 day cycle length) were assessed after cycles 2, 4, 6, 8 and so on treatment cycles.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Participants | Clinical Response Rate | Not Assessed | 1 Participants |
| All Participants | Clinical Response Rate | Partial Response | 0 Participants |
| All Participants | Clinical Response Rate | Stable Disease | 2 Participants |
| All Participants | Clinical Response Rate | Progressive Disease | 1 Participants |
| All Participants | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Clinical Response Rate | Partial Response | 0 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Clinical Response Rate | Progressive Disease | 3 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Clinical Response Rate | Not Assessed | 0 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Clinical Response Rate | Stable Disease | 0 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Clinical Response Rate | Progressive Disease | 1 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Clinical Response Rate | Not Assessed | 0 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Clinical Response Rate | Partial Response | 0 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Clinical Response Rate | Stable Disease | 2 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Clinical Response Rate | Partial Response | 0 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Clinical Response Rate | Stable Disease | 3 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Clinical Response Rate | Progressive Disease | 2 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Clinical Response Rate | Not Assessed | 1 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Clinical Response Rate | Not Assessed | 2 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Clinical Response Rate | Stable Disease | 4 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Clinical Response Rate | Partial Response | 0 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Clinical Response Rate | Progressive Disease | 3 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Clinical Response Rate | Stable Disease | 0 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Clinical Response Rate | Partial Response | 0 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Clinical Response Rate | Not Assessed | 0 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Clinical Response Rate | Progressive Disease | 2 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Clinical Response Rate | Stable Disease | 2 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Clinical Response Rate | Not Assessed | 1 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Clinical Response Rate | Progressive Disease | 1 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Clinical Response Rate | Partial Response | 0 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Clinical Response Rate | Partial Response | 0 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Clinical Response Rate | Not Assessed | 0 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Clinical Response Rate | Progressive Disease | 2 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Clinical Response Rate | Stable Disease | 1 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Clinical Response Rate | Not Assessed | 1 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Clinical Response Rate | Complete Response | 0 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Clinical Response Rate | Stable Disease | 0 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Clinical Response Rate | Partial Response | 0 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Clinical Response Rate | Progressive Disease | 3 Participants |
Secondary
Concentration of Drug in Plasma at Steady State (Css)
Concentration of drug in plasma at steady state (Css).
Time frame: Days 7 through 10
Population: 3/4 participants in dose level 1, and 2/3 participants in dose level 2 were not evaluable for this outcome measure. Css was only performed for the 10 day dosing cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Concentration of Drug in Plasma at Steady State (Css) | 44.5 pg/mL | — |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Concentration of Drug in Plasma at Steady State (Css) | 48.5 pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Concentration of Drug in Plasma at Steady State (Css) | 73.2 pg/mL | Geometric Coefficient of Variation 22.6 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Concentration of Drug in Plasma at Steady State (Css) | 489 pg/mL | Geometric Coefficient of Variation 463 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Concentration of Drug in Plasma at Steady State (Css) | 2020 pg/mL | Geometric Coefficient of Variation 2309 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Concentration of Drug in Plasma at Steady State (Css) | 9562 pg/mL | Geometric Coefficient of Variation 59.35 |
Secondary
Inflammatory Cytokines
Serum samples was obtained from participants and inflammatory cytokine analyses was performed by flow cytometry to determine levels of Interleukin - 1, Interferon γ, Interleukin-6 and Tumor Necrosis Factor ἁ.
Time frame: Pre, 0.16, 1, 2, 4, 8, 12, and 24 hours on Day 1. Days 2, 7, 8, 9, and 10. 0, 0.16, 0.32, 1, 2, 4, and 12 hours on Day 11. And 24 hours on Day 12.
Population: This outcome measure was only performed for 10 day dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 11 | 82 pg/mL | Standard Error 136 |
| All Participants | Inflammatory Cytokines | Interferon γ - 24 hours on Day 1 | 24.6 pg/mL | Standard Error 34 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 1 | 2.7 pg/mL | Standard Error 1.7 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 1 | 4 pg/mL | Standard Error 2.3 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 1 | 6.3 pg/mL | Standard Error 7 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 8 hours on Day 1 | 3 pg/mL | Standard Error 0.45 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 1 | 3.4 pg/mL | Standard Error 2.4 |
| All Participants | Inflammatory Cytokines | Interferon γ on Day 2 | 11.1 pg/mL | Standard Error 12 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 1 | 1.8 pg/mL | Standard Error 1 |
| All Participants | Inflammatory Cytokines | Interleukin-6, Pre Day 1 | 3.4 pg/mL | Standard Error 2.6 |
| All Participants | Inflammatory Cytokines | Interferon γ - 24 hours on Day 12 | 8.3 pg/mL | Standard Error 84.6 |
| All Participants | Inflammatory Cytokines | Interferon γ - 12 hours on Day 11 | NA pg/mL | — |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 1 | 1.7 pg/mL | Standard Error 0.8 |
| All Participants | Inflammatory Cytokines | Interferon γ - 1 hour on Day 11 | 12 pg/mL | Standard Error 12.4 |
| All Participants | Inflammatory Cytokines | Interferon γ - 0.32 hours on Day 11 | 11.6 pg/mL | Standard Error 12 |
| All Participants | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 11 | 11.3 pg/mL | Standard Error 12 |
| All Participants | Inflammatory Cytokines | Interferon γ on Day 9 | 15 pg/mL | Standard Error 20 |
| All Participants | Inflammatory Cytokines | Interferon γ on Day 8 | 13.2 pg/mL | Standard Error 18 |
| All Participants | Inflammatory Cytokines | Interleukin - 1 on Day 9 | 0.54 pg/mL | Standard Error 0.5 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 0 hours on Day 11 | 0.72 pg/mL | Standard Error 0.8 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 12 | 2.3 pg/mL | Standard Error 0.6 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 11 | 3.7 pg/mL | Standard Error 1.3 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 11 | 5.5 pg/mL | Standard Error 4 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 0.32 hours on Day 11 | 3.4 pg/mL | Standard Error 1.4 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 11 | 3.6 pg/mL | Standard Error 1.5 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 11 | 0.62 pg/mL | Standard Error 0.6 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 11 | NA pg/mL | — |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 0 hours on Day 11 | 3.7 pg/mL | Standard Error 2.4 |
| All Participants | Inflammatory Cytokines | Interleukin-6 on Day 10 | 3.8 pg/mL | Standard Error 2.4 |
| All Participants | Inflammatory Cytokines | Interleukin-6 on Day 8 | 4 pg/mL | Standard Error 4.4 |
| All Participants | Inflammatory Cytokines | Interleukin-6 on Day 7 | 15.2 pg/mL | Standard Error 17 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 0.32 hours on Day 11 | 0.69 pg/mL | Standard Error 0.7 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 11 | 2.7 pg/mL | Standard Error 0.9 |
| All Participants | Inflammatory Cytokines | Interleukin-6 on Day 2 | 2.2 pg/mL | Standard Error 0.7 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 1 | 5.1 pg/mL | Standard Error 4.3 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 1 | 4.1 pg/mL | Standard Error 4.2 |
| All Participants | Inflammatory Cytokines | Interferon γ - 4 hours on Day 1 | 9.4 pg/mL | Standard Error 6.8 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 11 | 8.69 pg/mL | Standard Error 13.3 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 11 | 4.4 pg/mL | Standard Error 2.2 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 1 | 3.7 pg/mL | Standard Error 3.8 |
| All Participants | Inflammatory Cytokines | Interferon γ - 4 hours on Day 11 | 12.5 pg/mL | Standard Error 13 |
| All Participants | Inflammatory Cytokines | Interferon γ - 2 hours on Day 11 | 8.6 pg/mL | Standard Error 8 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 11 | 1.2 pg/mL | Standard Error 1.1 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.32 hours on Day 11 | 2.5 pg/mL | Standard Error 1.5 |
| All Participants | Inflammatory Cytokines | Interferon γ - 0 hours on Day 11 | 11 pg/mL | Standard Error 11.4 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 11 | 2.2 pg/mL | Standard Error 0.6 |
| All Participants | Inflammatory Cytokines | Interferon γ on Day 10 | 13.3 pg/mL | Standard Error 16 |
| All Participants | Inflammatory Cytokines | Interferon γ on Day 7 | 10 pg/mL | Standard Error 10 |
| All Participants | Inflammatory Cytokines | Interferon γ - 1 hour on Day 1 | 6.5 pg/mL | Standard Error 5.5 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 11 | NA pg/mL | — |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0 hours on Day 11 | 2.4 pg/mL | Standard Error 1.2 |
| All Participants | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 1 | 2.5 pg/mL | Standard Error 1.6 |
| All Participants | Inflammatory Cytokines | Interferon γ, Pre Day 1 | 6.8 pg/mL | Standard Error 6.9 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 11 | 0.51 pg/mL | Standard Error 0.3 |
| All Participants | Inflammatory Cytokines | Interleukin - 1 on Day 7 | 1.18 pg/mL | Standard Error 0.9 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 12 | 0.44 pg/mL | Standard Error 0.3 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 9 | 2.6 pg/mL | Standard Error 1.2 |
| All Participants | Inflammatory Cytokines | Interleukin - 1 on Day 2 | 0.42 pg/mL | Standard Error 0.3 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 1 | 0.54 pg/mL | Standard Error 0.2 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 8 hours on Day 1 | 0.73 pg/mL | Standard Error 0.1 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 1 | 0.36 pg/mL | Standard Error 0.2 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 1 | 0.59 pg/mL | Standard Error 0.3 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 1 | 0.58 pg/mL | Standard Error 0.3 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 1 | 0.47 pg/mL | Standard Error 0.3 |
| All Participants | Inflammatory Cytokines | Interferon γ - 2 hours on Day 1 | 6.8 pg/mL | Standard Error 5.9 |
| All Participants | Inflammatory Cytokines | Interleukin - 1 on Day 8 | 0.43 pg/mL | Standard Error 0.3 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 1 | 0.28 pg/mL | Standard Error 0 |
| All Participants | Inflammatory Cytokines | Interleukin - 1, Pre Day 1 | 0.38 pg/mL | Standard Error 0.24 |
| All Participants | Inflammatory Cytokines | Interleukin - 1 on Day 10 | 0.45 pg/mL | Standard Error 0.3 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 11 | 1.9 pg/mL | Standard Error 0.6 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 10 | 2.7 pg/mL | Standard Error 1.6 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 8 | 2.7 pg/mL | Standard Error 0.9 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 7 | 2.9 pg/mL | Standard Error 0.5 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ Day 2 | 2.3 pg/mL | Standard Error 0.7 |
| All Participants | Inflammatory Cytokines | Interferon γ - 8 hours on Day 1 | 27 pg/mL | Standard Error 14 |
| All Participants | Inflammatory Cytokines | Interleukin-6 on Day 9 | 3.4 pg/mL | Standard Error 2.5 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 1 | 2.1 pg/mL | Standard Error 0.5 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 1 | 2.5 pg/mL | Standard Error 1 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 1 | 1.2 pg/mL | Standard Error 0.4 |
| All Participants | Inflammatory Cytokines | Interferon γ - 12 hours on Day 1 | 22.7 pg/mL | Standard Error 24 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 8 hours on Day 1 | 1.7 pg/mL | Standard Error 0.5 |
| All Participants | Inflammatory Cytokines | Tumor Necrosis Factor ἁ, Pre Day 1 | 1.85 pg/mL | Standard Error 0.8 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 12 | 2.9 pg/mL | Standard Error 0.7 |
| All Participants | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 2 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 9 | 6.8 pg/mL | Standard Error 5.4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 8 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0 hours on Day 11 | 0.27 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 11 | 2.98 pg/mL | Standard Error 4.7 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.32 hours on Day 11 | 0.26 pg/mL | Standard Error 0.4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 11 | 0.81 pg/mL | Standard Error 0.9 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 11 | 0.32 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 1 | 4.9 pg/mL | Standard Error 1 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 11 | 0.81 pg/mL | Standard Error 0.6 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 12 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 1 | 4 pg/mL | Standard Error 1 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 1 | 4.7 pg/mL | Standard Error 1.6 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 8 hours on Day 1 | 5 pg/mL | Standard Error 2.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 1 | 5.7 pg/mL | Standard Error 2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 1 | 6.6 pg/mL | Standard Error 1.1 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 2 | 8.1 pg/mL | Standard Error 2.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 7 | 8.6 pg/mL | Standard Error 1.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 8 | 9.5 pg/mL | Standard Error 0.4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 9 | 8.9 pg/mL | Standard Error 2.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 11 | 7.7 pg/mL | Standard Error 0.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.32 hours on Day 11 | 7.6 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 11 | 7.5 pg/mL | Standard Error 0.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 12 | 5.1 pg/mL | Standard Error 0.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6, Pre Day 1 | 5.3 pg/mL | Standard Error 4.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 1 | 5.3 pg/mL | Standard Error 3.7 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 8 hours on Day 1 | 6.6 pg/mL | Standard Error 5.4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 1 | 6.7 pg/mL | Standard Error 5.9 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 1 | 7.2 pg/mL | Standard Error 5.8 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 11 | 6.8 pg/mL | Standard Error 6.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 12 | 7.7 pg/mL | Standard Error 6.6 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ, Pre Day 1 | 2.3 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 1 | 1.7 pg/mL | Standard Error 0.7 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 1 | 2.6 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 1 | 2.9 pg/mL | Standard Error 0.7 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ Day 2 | 3.6 pg/mL | Standard Error 0.4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 7 | 3 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 8 | 3.5 pg/mL | Standard Error 1.5 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 11 | 3 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 11 | 4 pg/mL | Standard Error 3.8 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, Pre Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 8 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 7 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 9 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 10 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 11 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ, Pre Day 1 | 4.6 pg/mL | Standard Error 1.6 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 1 | 3.4 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 10 | 8.9 pg/mL | Standard Error 1.9 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0 hours on Day 11 | 7.8 pg/mL | Standard Error 1 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 11 | 5.5 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 11 | 7.6 pg/mL | Standard Error 1.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 1 | 5.2 pg/mL | Standard Error 4.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 1 | 6.6 pg/mL | Standard Error 5.4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 1 | 6.9 pg/mL | Standard Error 5.8 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 2 | 6.2 pg/mL | Standard Error 4.5 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 7 | 4.8 pg/mL | Standard Error 2.8 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 8 | 6.1 pg/mL | Standard Error 4.1 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 10 | 5.9 pg/mL | Standard Error 4.7 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0 hours on Day 11 | 7.7 pg/mL | Standard Error 6.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 11 | 6.8 pg/mL | Standard Error 6.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.32 hours on Day 11 | 113 pg/mL | Standard Error 184 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 11 | 45.7 pg/mL | Standard Error 66 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 11 | 8.5 pg/mL | Standard Error 7.6 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 1 | 2.3 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 1 | 2.4 pg/mL | Standard Error 1.4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 1 | 2.2 pg/mL | Standard Error 1.1 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 8 hours on Day 1 | 2.4 pg/mL | Standard Error 1.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 9 | 3.4 pg/mL | Standard Error 1.6 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 10 | 2.8 pg/mL | Standard Error 1.4 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0 hours on Day 11 | 2.9 pg/mL | Standard Error 1 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.32 hours on Day 11 | 14.2 pg/mL | Standard Error 20 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 11 | 2.9 pg/mL | Standard Error 0.9 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 11 | 2.9 pg/mL | Standard Error 1.3 |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 12 | 2.8 pg/mL | Standard Error 1 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 1 | 78 pg/mL | Standard Error 127 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 1 | 4.4 pg/mL | Standard Error 3.3 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 10 | 43 pg/mL | Standard Error 10.7 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 11 | 16.2 pg/mL | Standard Error 0 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 12 | 15.4 pg/mL | Standard Error 20 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0 hours on Day 11 | 57.4 pg/mL | Standard Error 34 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.32 hours on Day 11 | 41 pg/mL | Standard Error 1.1 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 1 | 4.4 pg/mL | Standard Error 1.1 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 11 | 16.3 pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.32 hours on Day 11 | 5.5 pg/mL | Standard Error 2.9 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 11 | 25.3 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 1 | 348 pg/mL | Standard Error 596 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 11 | 4 pg/mL | Standard Error 1.9 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 11 | 36.9 pg/mL | Standard Error 10 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 1 | 5.1 pg/mL | Standard Error 3.2 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0 hours on Day 11 | 11.6 pg/mL | Standard Error 12 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 11 | 0.45 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ Day 2 | 5.1 pg/mL | Standard Error 2.8 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 1 | 179 pg/mL | Standard Error 303 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 11 | 0.64 pg/mL | Standard Error 0.21 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 10 | 3.1 pg/mL | Standard Error 1 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 1 | 18.1 pg/mL | Standard Error 23 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 1 | 16 pg/mL | Standard Error 25 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 8 hours on Day 1 | 10.6 pg/mL | Standard Error 6.5 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.32 hours on Day 11 | 0.56 pg/mL | Standard Error 0.16 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 9 | 5.2 pg/mL | Standard Error 5.2 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 2 | 6.2 pg/mL | Standard Error 5.3 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6, Pre Day 1 | 200 pg/mL | Standard Error 342 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 8 | 2.9 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 11 | 4.9 pg/mL | Standard Error 2.5 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 7 | 6.6 pg/mL | Standard Error 4.9 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 7 | 5.5 pg/mL | Standard Error 4.5 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 1 | 6.3 pg/mL | Standard Error 8 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 2 | 17 pg/mL | Standard Error 10.1 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 8 | 5.6 pg/mL | Standard Error 4.3 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 11 | 5 pg/mL | Standard Error 2.7 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 1 | 6.8 pg/mL | Standard Error 3.2 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 11 | 4.7 pg/mL | Standard Error 1.6 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 12 | 19 pg/mL | Standard Error 6.4 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 2 | 0.94 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 12 | 30.4 pg/mL | Standard Error 27 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 1 | 13.3 pg/mL | Standard Error 8 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 1 | 11.2 pg/mL | Standard Error 7.4 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 9 | 5.3 pg/mL | Standard Error 3.3 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, Pre Day 1 | 9.8 pg/mL | Standard Error 15.9 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 8 | 0.25 pg/mL | Standard Error 0.2 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 11 | 37.5 pg/mL | Standard Error 4.7 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 1 | 6.9 pg/mL | Standard Error 4.4 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 1 | 2.2 pg/mL | Standard Error 3 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ, Pre Day 1 | 12.4 pg/mL | Standard Error 18 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 7 | 56 pg/mL | Standard Error 55 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 10 | 5.6 pg/mL | Standard Error 3.8 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 1 | 4.4 pg/mL | Standard Error 6.8 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 1 | 8.4 pg/mL | Standard Error 8 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 1 | 13.4 pg/mL | Standard Error 21 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 8 hours on Day 1 | 4.9 pg/mL | Standard Error 2.5 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 11 | 37.8 pg/mL | Standard Error 6 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 8 hours on Day 1 | 1.3 pg/mL | Standard Error 1.4 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 1 | 39 pg/mL | Standard Error 66 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 1 | 0.36 pg/mL | Standard Error 0.2 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 1 | 0.62 pg/mL | Standard Error 0.65 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 9 | 26.8 pg/mL | Standard Error 21 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 1 | 24 pg/mL | Standard Error 39 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 7 | 0.44 pg/mL | Standard Error 0.35 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 11 | 16 pg/mL | Standard Error 13.5 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 8 | 55.7 pg/mL | Standard Error 57 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0 hours on Day 11 | 6.3 pg/mL | Standard Error 1.9 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 9 | 0.76 pg/mL | Standard Error 0.23 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 10 | 0.59 pg/mL | Standard Error 0.13 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 1 | 17.9 pg/mL | Standard Error 30 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 8 hours on Day 1 | 3.6 pg/mL | Standard Error 2.2 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 1 | 3.9 pg/mL | Standard Error 2.4 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 11 | 13.3 pg/mL | Standard Error 10 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 12 | 16.2 pg/mL | Standard Error 27 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0 hours on Day 11 | 0.69 pg/mL | Standard Error 0.21 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ, Pre Day 1 | 8.3 pg/mL | Standard Error 8.9 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 11 | 14.6 pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 1 | 5.7 pg/mL | Standard Error 4.7 |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.32 hours on Day 11 | 19.7 pg/mL | Standard Error 13 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ, Pre Day 1 | 4.7 pg/mL | Standard Error 3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 8 hours on Day 1 | 4.3 pg/mL | Standard Error 1.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 11 | 4.7 pg/mL | Standard Error 3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 11 | 0.75 pg/mL | Standard Error 0.6 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 1 | 2.5 pg/mL | Standard Error 1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 11 | 89 pg/mL | Standard Error 77 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 10 | 262 pg/mL | Standard Error 432 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 1 | 6.4 pg/mL | Standard Error 2.1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 11 | 7.9 pg/mL | Standard Error 8.9 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 1 | 4.5 pg/mL | Standard Error 2.9 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 11 | 2.17 pg/mL | Standard Error 1.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 8 | 52.9 pg/mL | Standard Error 36 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, Pre Day 1 | 0.86 pg/mL | Standard Error 0.8 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 11 | 106 pg/mL | Standard Error 119 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 2 | 0.43 pg/mL | Standard Error 0.3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 1 | 5 pg/mL | Standard Error 1.9 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 1 | 6.2 pg/mL | Standard Error 6.4 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 7 | 0.32 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 9 | 6.6 pg/mL | Standard Error 2.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 11 | 96.6 pg/mL | Standard Error 93 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 11 | 5.1 pg/mL | Standard Error 1.8 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 1 | 19 pg/mL | Standard Error 45 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 11 | 0.75 pg/mL | Standard Error 0.6 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.32 hours on Day 11 | 6 pg/mL | Standard Error 1.3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.32 hours on Day 11 | 5.1 pg/mL | Standard Error 1.8 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0 hours on Day 11 | 7.1 pg/mL | Standard Error 7.6 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 12 | 0.34 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ, Pre Day 1 | 2.2 pg/mL | Standard Error 0.9 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.32 hours on Day 11 | 101 pg/mL | Standard Error 123 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 1 | 4 pg/mL | Standard Error 3.3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 8 | 4.3 pg/mL | Standard Error 1.9 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 1 | 3.7 pg/mL | Standard Error 3.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ Day 2 | 6.8 pg/mL | Standard Error 2.3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0 hours on Day 11 | 6.6 pg/mL | Standard Error 1.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 10 | 5.6 pg/mL | Standard Error 3.1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 1 | 3.5 pg/mL | Standard Error 8 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 1 | 5.1 pg/mL | Standard Error 3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 1 | 3.2 pg/mL | Standard Error 2.2 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 7 | 43.8 pg/mL | Standard Error 29 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 11 | 0.72 pg/mL | Standard Error 0.4 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6, Pre Day 1 | 2.1 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 1 | 9.1 pg/mL | Standard Error 20 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 1 | 17 pg/mL | Standard Error 23 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 1 | 2.9 pg/mL | Standard Error 1.6 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 10 | 7.4 pg/mL | Standard Error 2 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 1 | 4.7 pg/mL | Standard Error 1.9 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 10 | 0.3 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 1 | 0.53 pg/mL | Standard Error 0.3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 8 hours on Day 1 | 24 pg/mL | Standard Error 20 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 2 | 3.4 pg/mL | Standard Error 1.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 11 | 99 pg/mL | Standard Error 111 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 11 | 6.4 pg/mL | Standard Error 1.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 1 | 2.9 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.32 hours on Day 11 | 0.65 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 7 | 3.2 pg/mL | Standard Error 0.9 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 8 hours on Day 1 | 0.83 pg/mL | Standard Error 0.8 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 7 | 7.5 pg/mL | Standard Error 2.1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 11 | 5.4 pg/mL | Standard Error 1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 1 | 11 pg/mL | Standard Error 7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 1 | 2.7 pg/mL | Standard Error 1.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 8 | 7.7 pg/mL | Standard Error 2 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 9 | 4.7 pg/mL | Standard Error 2 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0 hours on Day 11 | 451 pg/mL | Standard Error 794 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 12 | 27.4 pg/mL | Standard Error 27 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 11 | 12.2 pg/mL | Standard Error 16 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 1 | 29 pg/mL | Standard Error 14.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 9 | 132 pg/mL | Standard Error 183 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 11 | 6.5 pg/mL | Standard Error 1.6 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 1 | 32.8 pg/mL | Standard Error 19 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 1 | 0.5 pg/mL | Standard Error 0.3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 8 | 0.36 pg/mL | Standard Error 0.3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 1 | 1.2 pg/mL | Standard Error 1.4 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 1 | 3.40 pg/mL | Standard Error 2 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 12 | 3.3 pg/mL | Standard Error 1.1 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 12 | 3.5 pg/mL | Standard Error 0.7 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0 hours on Day 11 | 1.1 pg/mL | Standard Error 0.8 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 2 | 58.4 pg/mL | Standard Error 47 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 9 | 0.38 pg/mL | Standard Error 0.3 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 8 hours on Day 1 | 6.6 pg/mL | Standard Error 3.4 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 11 | 0.42 pg/mL | Standard Error 0.3 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 8 | 8.8 pg/mL | Standard Error 9.1 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 11 | 9.8 pg/mL | Standard Error 8.8 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 1 | 66.6 pg/mL | Standard Error 39 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 1 | 5.5 pg/mL | Standard Error 3.7 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 12 | 8.3 pg/mL | Standard Error 9.38 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ, Pre Day 1 | 2.4 pg/mL | Standard Error 0.6 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 8 hours on Day 1 | 110 pg/mL | Standard Error 170 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 1 | 7.8 pg/mL | Standard Error 15 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 1 | 8.6 pg/mL | Standard Error 3.3 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 1 | 11.5 pg/mL | Standard Error 6.4 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 8 hours on Day 1 | 13.3 pg/mL | Standard Error 20 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ Day 2 | 11.6 pg/mL | Standard Error 4.7 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 1 | 131 pg/mL | Standard Error 289 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 7 | 13.8 pg/mL | Standard Error 2.7 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 8 | 13.4 pg/mL | Standard Error 2.9 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 9 | 11.2 pg/mL | Standard Error 3.7 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 1 | 7 pg/mL | Standard Error 19.7 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 11 | 9.8 pg/mL | Standard Error 2.4 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 11 | 7.7 pg/mL | Standard Error 2 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 12 | 5 pg/mL | Standard Error 1.4 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 9 | 0.42 pg/mL | Standard Error 0.4 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 1 | 11.5 pg/mL | Standard Error 7.2 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, Pre Day 1 | 0.34 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 1 | 77 pg/mL | Standard Error 229 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 1 | 10.6 pg/mL | Standard Error 10 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 1 | 22 pg/mL | Standard Error 65 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 1 | 6.3 pg/mL | Standard Error 16 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 10 | 11.1 pg/mL | Standard Error 3.6 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 8 hours on Day 1 | 209 pg/mL | Standard Error 605 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ, Pre Day 1 | 9.2 pg/mL | Standard Error 6.3 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 1 | 4.3 pg/mL | Standard Error 8 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 2 | 1.1 pg/mL | Standard Error 1.5 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 7 | 0.27 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 10 | 0.37 pg/mL | Standard Error 0.2 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0 hours on Day 11 | 10.7 pg/mL | Standard Error 3 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 11 | 0.52 pg/mL | Standard Error 0.4 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 12 | 0.27 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 1 | 21 pg/mL | Standard Error 40 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 1 | 19 pg/mL | Standard Error 24 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 8 | 145 pg/mL | Standard Error 109 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 1 | 57 pg/mL | Standard Error 170 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 10 | 238 pg/mL | Standard Error 214 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 11 | 204 pg/mL | Standard Error 172 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 11 | 0.6 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 11 | 101 pg/mL | Standard Error 170 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 1 | 232 pg/mL | Standard Error 682 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.32 hours on Day 11 | 9.4 pg/mL | Standard Error 2.3 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 1 | 262 pg/mL | Standard Error 773 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 1 | 120 pg/mL | Standard Error 349 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.32 hours on Day 11 | 0.56 pg/mL | Standard Error 0.4 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 1 | 23.7 pg/mL | Standard Error 30 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 2 | 13.2 pg/mL | Standard Error 14 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 7 | 8 pg/mL | Standard Error 7.2 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 11 | 0.61 pg/mL | Standard Error 0.6 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 9 | 9.9 pg/mL | Standard Error 9.2 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 11 | 9.7 pg/mL | Standard Error 2.4 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 10 | 12 pg/mL | Standard Error 14 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0 hours on Day 11 | 10.2 pg/mL | Standard Error 8.6 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 11 | 11.4 pg/mL | Standard Error 9.7 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0 hours on Day 11 | 0.62 pg/mL | Standard Error 0.6 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.32 hours on Day 11 | 11.4 pg/mL | Standard Error 9.2 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 11 | 11.2 pg/mL | Standard Error 8.9 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 11 | 9 pg/mL | Standard Error 2.1 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 11 | 11.4 pg/mL | Standard Error 10 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 1 | 13.5 pg/mL | Standard Error 34 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 9 | 149 pg/mL | Standard Error 112 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0 hours on Day 11 | 315 pg/mL | Standard Error 327 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 7 | 136 pg/mL | Standard Error 74 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 11 | 223 pg/mL | Standard Error 180 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 1 | 11.2 pg/mL | Standard Error 27 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.32 hours on Day 11 | 207 pg/mL | Standard Error 177 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 11 | 190 pg/mL | Standard Error 141 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 2 | 230 pg/mL | Standard Error 205 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 8 | 0.29 pg/mL | Standard Error 0.1 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 12 | 97 pg/mL | Standard Error 145 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6, Pre Day 1 | 7.1 pg/mL | Standard Error 9.6 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 1 | 106 pg/mL | Standard Error 84 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 8 hours on Day 1 | 607 pg/mL | Standard Error 1767 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 1 | 18.4 pg/mL | Standard Error 27 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 2 | 639 pg/mL | Standard Error 678 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 8 hours on Day 1 | 97 pg/mL | Standard Error 67 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 1 | 94.6 pg/mL | Standard Error 38 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 1 | 2.9 pg/mL | Standard Error 1.9 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 1 | 2.5 pg/mL | Standard Error 0.6 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 1 | 131 pg/mL | Standard Error 3.3 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 1 | 9.2 pg/mL | Standard Error 2.8 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 12 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 2 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 1 hour on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 1 | 45.6 pg/mL | Standard Error 59 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 1 | 1.9 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 8 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 10 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 7 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 8 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 7 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 2 | 0.7 pg/mL | Standard Error 0.6 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 24 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 12 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.32 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 10 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 1 | 6.3 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ, Pre Day 1 | 1.8 pg/mL | Standard Error 0.5 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 8 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ, Pre Day 1 | 2.8 pg/mL | Standard Error 1 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 4 hours on Day 1 | 0.36 pg/mL | Standard Error 0.2 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 12 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 2 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 8 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 8 hours on Day 1 | 16.9 pg/mL | Standard Error 9.4 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.32 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 1 | 1.7 pg/mL | Standard Error 0.4 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, Pre Day 1 | 0.24 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 4 hours on Day 1 | 6 pg/mL | Standard Error 1.2 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 4 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 4 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 0.16 hours on Day 1 | 1.72 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1 on Day 9 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 1 | 38.7 pg/mL | Standard Error 13 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 24 hours on Day 12 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 1 | 7 pg/mL | Standard Error 2 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.16 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 9 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 7 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 24 hours on Day 1 | 12.7 pg/mL | Standard Error 10 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.16 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 2 | 141 pg/mL | Standard Error 112 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 12 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 8 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 9 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 2 hours on Day 1 | 3.8 pg/mL | Standard Error 3.5 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ on Day 7 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 0.32 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0.32 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 8 hours on Day 1 | 6 pg/mL | Standard Error 3 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 on Day 10 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 1 hour on Day 1 | 3.9 pg/mL | Standard Error 3.7 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ - 1 hour on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 1 | 6.8 pg/mL | Standard Error 0 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 24 hours on Day 12 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Tumor Necrosis Factor ἁ Day 2 | 24 pg/mL | Standard Error 7 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin - 1, 0 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 2 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ - 1 hour on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 10 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 12 hours on Day 1 | 7.3 pg/mL | Standard Error 4.8 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6 - 0.16 hours on Day 11 | NA pg/mL | — |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interleukin-6, Pre Day 1 | 4.6 pg/mL | Standard Error 4.7 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Inflammatory Cytokines | Interferon γ on Day 9 | NA pg/mL | — |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15)
The maximum observed analyte concentration in serum was reported.
Time frame: Prior to 1st dose, at 10 minutes after 1st dose, once daily on days 7-10 at completion of treatment, at 10 and 30 minutes after completion of treatment and at 1, 2, 4, and approximately 24 hours after completion of treatment.
Population: 3/4 participants in dose level 1, and 2/3 participants in dose level 2 were not evaluable for this outcome measure. Cmax was only performed for the 10 day dosing cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15) | 51 pg/mL | — |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15) | 59 pg/mL | — |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15) | 116 pg/mL | Geometric Coefficient of Variation 72 |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15) | 1413 pg/mL | Geometric Coefficient of Variation 1478 |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15) | 5662 pg/mL | Geometric Coefficient of Variation 5961 |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15) | 26852 pg/mL | Geometric Coefficient of Variation 11374 |
Secondary
Time to Progression (TTP)
TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.
Time frame: From the date of protocol consent until date of progressive disease is documented, up to 263 days
Population: One participant in dose level 1 and dose level 2, two participants in dose level 3, three participants in dose level 4, two participants in dose level 5, one participant in dose level 6 and dose level 7, and one participant in dose level 9 were not evaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Time to Progression (TTP) | 74 Days |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Time to Progression (TTP) | 54 Days |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Time to Progression (TTP) | 29 Days |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Time to Progression (TTP) | 77 Days |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Time to Progression (TTP) | 68 Days |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Time to Progression (TTP) | 6 Days |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Time to Progression (TTP) | 87 Days |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Time to Progression (TTP) | 42 Days |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Time to Progression (TTP) | 34.5 Days |
Other Pre-specified
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Date treatment consent signed to date off study, approximately 18 months (m)/27 days(d), 3 m, 9 m/13d, 15 m/20d, 28 m/17d, 1 m/23d, 15 m/8d, 4 m/5d, and 6 m/30d for levels 1-9 respectively.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 4 Participants |
| Dose Escalation Level 2 - 0.25 mcg/kg/Day x 10 Days | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 3 Participants |
| Dose Escalation Level 3 - 0.5 mcg/kg/Day x 10 Days | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 3 Participants |
| Dose Escalation Level 4 - 1 mcg/kg/Day x 10 Days | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 6 Participants |
| Dose Escalation Level 5 - 2 mcg/kg/Day x 10 Days | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 9 Participants |
| Dose Escalation Level 6 - 4 mcg/kg/Day x 10 Days | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 2 Participants |
| Dose Escalation Level 7 - 3 mcg/kg/Day x 5 Days | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 4 Participants |
| Dose Escalation Level 8 - 4 mcg/kg/Day x 5 Days | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 3 Participants |
| Dose Escalation Level 9 - 5 mcg/kg/Day x 5 Days | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 4 Participants |