Clinical trial NCT04176133: Entolimod on Immunosenescence in Healthy Geriatric Subjects Receiving Influenza Vaccination
Official title: A Randomized, Double-Blind, Placebo-Controlled, Single-Administration, Dose-Escalation Study of Entolimod on Immunosenescence in Healthy Geriatric Subjects Receiving Influenza Vaccination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy
Keywords: Vaccination
Geriatric
Immunology
Influenza
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Genome Protection, Inc.
First posted: 2019-11-25
Enrollment: 61
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).


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.

Primary outcomes:
measure: Change in Anti- A/H1N1 Antibody Titer
timeFrame: Baseline, 1 month
measure: Change in Anti-A/H3N2 Antibody Titer
timeFrame: Baseline, 1 month
measure: Change in Anti-B Antibody Titer
timeFrame: Baseline, 1 month
measure: Adverse Events
timeFrame: 1 year
Secondary outcomes:
measure: Time of Onset for Upper-respiratory Infections
timeFrame: 1 year
measure: Upper Respiratory Infections
timeFrame: 1 year
measure: Change in Frailty
timeFrame: baseline, 2 months
measure: Change in 6-minute Walk Test
timeFrame: baseline, 2 months
measure: Change in Grip Strength
timeFrame: baseline, 2 months
measure: Change in Body Mass Index (BMI)
timeFrame: baseline, 2 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Robert Pignolo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: