Entolimod on Immunosenescence in Healthy Geriatric Subjects Receiving Influenza Vaccination

Robert J. Pignolo

Status and phase: Completed; Phase 2

Conditions: Healthy

Treatments: Drug: Influenza vaccine; Drug: Entolimod; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04176133

19-004847

Details and patient eligibility

About

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).

Enrollment: 61 patients

Sex: All

Ages: 65+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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61 participants in 4 patient groups, including a placebo group

Entolimod 1 mcg

Experimental group

Description:

Subjects will receive entolimod as a single dose administered intramuscularly (1mcg)

Treatment:

Drug: Entolimod

Drug: Influenza vaccine

Entolimod 3 mcg

Experimental group

Description:

Subjects will receive entolimod as a single dose administered intramuscularly (3mcg)

Treatment:

Drug: Entolimod

Drug: Influenza vaccine

Entolimod 10 mcg

Experimental group

Description:

Subjects will receive entolimod as a single dose administered intramuscularly (10mcg)

Treatment:

Drug: Entolimod

Drug: Influenza vaccine

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Influenza vaccine