Entolimod on Immunosenescence in Healthy Geriatric Subjects Receiving Influenza Vaccination

Study Overview
=================
Brief Summary
-----------------
Researchers are evaluating the safety and effectiveness of a single administration of entolimod when administered at the same time as the influenza vaccine (flu vaccine).

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Single-Administration, Dose-Escalation Study of Entolimod on Immunosenescence in Healthy Geriatric Subjects Receiving Influenza Vaccination

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Entolimod
* Drug: Placebo
* Drug: Influenza vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion: Men and women of age 65 years and older at the time of enrollment Eligible to receive Fluzone High-Dose Female subjects must be past menopause and not pregnant No history of anaphylactic reaction to gelatin, neomycin, or other vaccine component Must not have had the flu vaccine within the past 90 days Medically stable with no exacerbations or changes in medication regimen for chronic diseases in the past 3 months and no hospitalizations in the past 6 months Must be able to read/write English in order to provide informed consent and comply with study procedures Expected to be available for the duration of the study Exclusion: Receipt of any other vaccines within the past 30 days prior to enrollment Acute illness within the last 7 days History of hypersensitivity to the flu vaccine or its components (including gelatin, formaldehyde, octoxinol, thimerosal, and chicken protein). History of Guillain Barré syndrome (GBS) History of bleeding disorders Medical contraindication to treatment with vaccine as indicated by a history of autoimmune disease, immune deficiency, or hypersensitivity to other vaccines. Unstable major cardiovascular, renal, endocrine, immunological or hepatic disorder Systolic blood pressure (SBP) < 110 mmHg or orthostatic hypotension [>20 mmHg fall in SBP or >10 mmHg fall in diastolic blood pressure (DBP) with standing] at the time of screening. Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) (within 14 days prior to entolimod administration). Note: Subjects with localized fungal infections of skin or nails are eligible. Clinical signs of febrile illness (temperature >99.5oF) Baseline vital signs with ≥Grade 2 abnormalities Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism, venous thromboembolism) within 6 months prior to study drug administration; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; or uncontrolled Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg) despite antihypertensive therapy. o Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation, 2nd-degree atrioventricular (AV) block type II, 3rd degree AV block, or Grade ≥2 bradycardia (within 14 days prior to entolimod administration). Inadequate hepatic function (within 14 days prior to entolimod administration): Serum alanine aminotransferase (ALT) ≥3 × upper limit of normal (ULN) (Grade ≥1). Serum aspartate aminotransferase (AST) ≥3 × ULN (Grade ≥1) Serum alkaline phosphatase (ALP) ≥5 × ULN (Grade ≥2) Serum bilirubin ≥1.5 × ULN (Grade ≥1) Positive antiviral serology: Positive hepatitis C virus (HCV) antibody or positive HCV ribonucleic acid (RNA) by quantitative PCR. Positive hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) antibody or undetectable hepatitis B (HBV) deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction (PCR) testing. Positive human immunodeficiency virus (HIV) antibody. Use of medication that might interact with the flu vaccine including (but not limited to) specifically: aminopyrine, phenytoin sodium, theophylline, and warfarin sodium. Any ongoing treatment with immunosuppressive or immune-stimulant therapy Ongoing use of systemic corticosteroids. Blood or blood products given within the three months prior to vaccination and two months after vaccination Current and/or expected receipt of chemotherapy, radiation therapy or any other cytotoxic or immunosuppressive therapy [i.e. more than 10 mg of prednisone given daily or on alternative days for 2 weeks or more in the past 3 months] Receipt of another investigational pharmaceutical product within 60 days of treatment Diagnosis of Parkinson's Disease, previous stroke, or significant cognitive impairment (defined as MMSE <20) Other concerns that in the opinion of the PI would preclude a subject from participating in study procedures or from completing the study.

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entolimod 1 mcg<br>Subjects will receive entolimod as a single dose administered intramuscularly (1mcg) | Drug: Entolimod<br>* Intramuscular (IM) single dose administration. Entolimod is provided as a sterile, clear, colorless or slightly yellow liquid for IM injection.<br>* Other names: CBLB502;Drug: Influenza vaccine<br>* Intramuscular (IM) single dose administration. Fluzone, high-dose split virion influenza virus vaccine, Sanofi Pasteur<br>* Other names: Fluzone;|
| Experimental: Entolimod 3 mcg<br>Subjects will receive entolimod as a single dose administered intramuscularly (3mcg) | Drug: Entolimod<br>* Intramuscular (IM) single dose administration. Entolimod is provided as a sterile, clear, colorless or slightly yellow liquid for IM injection.<br>* Other names: CBLB502;Drug: Influenza vaccine<br>* Intramuscular (IM) single dose administration. Fluzone, high-dose split virion influenza virus vaccine, Sanofi Pasteur<br>* Other names: Fluzone;|
| Experimental: Entolimod 10 mcg<br>Subjects will receive entolimod as a single dose administered intramuscularly (10mcg) | Drug: Entolimod<br>* Intramuscular (IM) single dose administration. Entolimod is provided as a sterile, clear, colorless or slightly yellow liquid for IM injection.<br>* Other names: CBLB502;Drug: Influenza vaccine<br>* Intramuscular (IM) single dose administration. Fluzone, high-dose split virion influenza virus vaccine, Sanofi Pasteur<br>* Other names: Fluzone;|
| Placebo Comparator: Placebo<br>Subjects will receive a placebo as a single dose administered intramuscularly (no study drug); placebo that looks exactly like the study drug, but contains no active ingredient. | Drug: Placebo<br>* Intramuscular (IM) single dose administration, no active ingredient. A matching placebo is provided as a sterile, clear, colorless to slightly yellow liquid for IM injection in prefilled vials that are identical in appearance to the vials containing active drug.<br>Drug: Influenza vaccine<br>* Intramuscular (IM) single dose administration. Fluzone, high-dose split virion influenza virus vaccine, Sanofi Pasteur<br>* Other names: Fluzone;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Anti- A/H1N1 Antibody Titer | Change of the anti- A/H1N1 influenza virus strains serum circulating antibodies (as assessed using hemagglutination inhibition (HAI) assay) levels from baseline to 1 month. | Baseline, 1 month | 
| Change in Anti-A/H3N2 Antibody Titer | Change of the anti-A/H3N2 influenza virus strains serum circulating antibodies (as assessed using hemagglutination inhibition (HAI) assay) levels from baseline to 1 month. | Baseline, 1 month | 
| Change in Anti-B Antibody Titer | Change of the anti-B influenza virus strains serum circulating antibodies (as assessed using hemagglutination inhibition (HAI) assay) levels from baseline to 1 month.. | Baseline, 1 month | 
| Adverse Events | The number of adverse events (AEs) related to dose limiting toxicities (DLTs); laboratory abnormalities; oxygen saturation and vital sign changes, and adverse electrocardiogram (ECG) findings for 1 year | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Onset for Upper-respiratory Infections | Subject self-reporting of the number of days to develop an upper-respiratory infection | 1 year | 
| Upper Respiratory Infections | The total number of subjects to self-report an upper-respiratory infection | 1 year | 
| Change in Frailty | Change in self-reported 5 items frail scale. Frail scale scores range from 0-5, 1 point for each component, 0 = best 5 = worst (robust=0 points; pre-frail=0-1 points; frail 3-5 points) | baseline, 2 months | 
| Change in 6-minute Walk Test | Distance a subject is able to walk over 6 minutes over a hard flat surface | baseline, 2 months | 
| Change in Grip Strength | Measured by a grip dynamometer as reported in units of pounds. | baseline, 2 months | 
| Change in Body Mass Index (BMI) | Subject's BMI calculated as weight in kilograms divided by height in meters squared. Uses measurements of height and weight obtained during study (with appropriate metric conversions) | baseline, 2 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunology, Influenza, Vaccination, Geriatric