Entolimod, an Adjuvant for Vaccine Augmentation

NCT03063736 | Completed Early Phase 1 FDA Drug

• 1 other identifier: H-39354
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this pilot study to evaluate the safety of low dose Entolimod in normal, healthy, non-patient normals. This clinical trial in 40 normal humans compares a single dose of 4 ug Td (2 ug of TT and 2 ug of diphtheria toxoid + 3000 ug of alum with or without entolimod. Subjects will be randomized to: Td alone (n=15) and Td+ entolimod (n=25). The investigators expect that Td + entolimod will double the anti-TT and anti-diphtheria AB levels over Td alone.

Conditions

Substance Use Disorders

Outcome Measures

Primary Outcomes (1)

• Adverse events associated with entolimod augmentation.

  The proposed dose of entolimod used in our study is 30-40 times lesser than that previously given safely to humans. Although our pre-clinical data suggest that these very low levels of entolimod efficiently enhances the antibody levels to TT vaccine in rodents, the safety and success rate at these low doses of entolimod to enhance anti-TT AB in humans requires examination.

  6 weeks

Secondary Outcomes (1)

• Antibody titer comparison with entolimod augmentation of Td vaccine

  6 weeks

Study Arms (2)

Td vaccine with entolimod

EXPERIMENTAL

Td vaccine (4 ug) + Entolimod (1 ug) (n=25)

Drug: Entolimod; Biological: Td Vaccine

Td vaccine only

PLACEBO COMPARATOR

Td vaccine (4 ug) (n=15)

Biological: Td Vaccine

Interventions

Entolimod DRUG

The objective is to compare adverse events and anti-tetanus (TT) antibody levels between patients getting entolimod vs no entolimod combined with tetanus-diphtheria (Td) vaccine. This clinical trial in 40 normal health subjects compares a single dose of 4 ug Td (2 ug of TT and 2 ug of diphtheria toxoid + 3000 ug of alum) with or without entolimod (1μg).

Also known as: CBLB502

Td vaccine with entolimod

Td Vaccine BIOLOGICAL

The objective is to compare adverse events and anti-tetanus (TT) antibody levels between patients getting entolimod vs no entolimod combined with tetanus-diphtheria (Td) vaccine. This clinical trial in 40 normal health subjects compares a single dose of 4 ug Td (2 ug of TT and 2 ug of diphtheria toxoid + 3000 ug of alum) with or without entolimod (1μg).

Also known as: Tetanus and Diphtheria Toxoids Adsorbed

Td vaccine only; Td vaccine with entolimod

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, non-patient normal males between 18 and 40 years of age
• No baseline anti-TT AB (tetanus toxoid antibody) levels greater than 5 µg/ml
• Able to read/write/understand English and provide signed written informed consent prior to any study specific procedures.

You may not qualify if:

• Inability to read/write English
• Inability to provide written informed consent.
• Any major cardiovascular, renal, endocrine, immunological (including positive test result for human immunodeficiency virus types 1 or 2 antibodies) or hepatic disorder (including positive test result for hepatitis B, hepatitis C virus antibodies, or liver function tests (LFT's)(SGOT, SGPT) that are 20% greater than normal levels or history of severe alcohol use disorder (defined as a score of 5 of greater on the MINI, based on DSM criteria).
• Medical contraindication to treatment with vaccine as indicated by a history of autoimmune disease, immune deficiency, or hypersensitivity to other vaccines. Specific disorders include a prior Arthus-type hypersensitivity reaction to tetanus vaccine or any of its components, prior Guillain-Barre Syndrome, Ongoing active infection of any kind with clinical signs of febrile illness (temperature \>99.5ºF).
• Use of psychoactive or hepatotoxic medications or medications that might interact with the tetanus toxoid based vaccine including steroids within 30 days of screening, immunosuppressive or immunostimulant therapy.
• Received other vaccines, including flu vaccine, within 30 days prior to screening or Tetanus vaccine within 5 years of this study (Advisory Committee on Immunization Practices (ACIP) guidelines.
• Blood or blood products given in the 3 months prior to vaccination.
• Participation in another investigational pharmaceutical trial within 30 days prior to screening.
• Greater than Grade 1 abnormality in baseline safety labs (e.g, CBC and CMP), as defined using the FDA Guidance Document entitled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials"
• Greater than Grade 1 abnormality in baseline vital signs
• Women, as a standard safety measure, will be excluded from the study due to childbearing potential and to minimize the effects of differences in hormonal levels during the menstrual cycle and of sex differences in antibody titer responses to vaccines. Furthermore, our sample size is too small to control for these effects in women.
• Other concerns that in the PI's judgment will be a potential safety issue for the subject including cognitive impairment that precludes the ability to provide informed consent, and individuals with behavioral issues evidenced during screening or through the course of the trial that are disruptive and/or pose a safety concern to self or other subjects.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (5)

• Krivokrysenko VI, Toshkov IA, Gleiberman AS, Krasnov P, Shyshynova I, Bespalov I, Maitra RK, Narizhneva NV, Singh VK, Whitnall MH, Purmal AA, Shakhov AN, Gudkov AV, Feinstein E. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates. PLoS One. 2015 Sep 14;10(9):e0135388. doi: 10.1371/journal.pone.0135388. eCollection 2015.

  PMID: 26367124 BACKGROUND

• Krivokrysenko VI, Shakhov AN, Singh VK, Bone F, Kononov Y, Shyshynova I, Cheney A, Maitra RK, Purmal A, Whitnall MH, Gudkov AV, Feinstein E. Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure. J Pharmacol Exp Ther. 2012 Nov;343(2):497-508. doi: 10.1124/jpet.112.196071. Epub 2012 Jul 26.

  PMID: 22837010 BACKGROUND

• Leigh ND, Bian G, Ding X, Liu H, Aygun-Sunar S, Burdelya LG, Gudkov AV, Cao X. A flagellin-derived toll-like receptor 5 agonist stimulates cytotoxic lymphocyte-mediated tumor immunity. PLoS One. 2014 Jan 14;9(1):e85587. doi: 10.1371/journal.pone.0085587. eCollection 2014.

  PMID: 24454895 BACKGROUND

• Howell BA, Siler SQ, Shoda LK, Yang Y, Woodhead JL, Watkins PB. A mechanistic model of drug-induced liver injury AIDS the interpretation of elevated liver transaminase levels in a phase I clinical trial. CPT Pharmacometrics Syst Pharmacol. 2014 Feb 5;3(2):e98. doi: 10.1038/psp.2013.74.

  PMID: 24500662 BACKGROUND

• Danilova E, Shiryayev A, Kristoffersen EK, Sjursen H. Attenuated immune response to tetanus toxoid in young healthy men protected against tetanus. Vaccine. 2005 Oct 10;23(42):4980-3. doi: 10.1016/j.vaccine.2005.05.028.

  PMID: 15985319 BACKGROUND

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

CBLB502; Diphtheria-Tetanus Vaccine; Tetanus Toxoid

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Vaccines, Combined

Study Officials

• Thomas Kosten, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Waggoner Chair and Professor of Psychiatry, Neuroscience, Pharmacology, Immunology & Pathology Director, Dan Duncan Institute for Clinical and Translational Research

Study Record Dates

• First Submitted: February 21, 2017
• First Posted: February 24, 2017
• Study Start: December 8, 2017
• Primary Completion: March 9, 2018
• Study Completion: December 31, 2019
• Last Updated: September 1, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)