Evaluation of Safety, Tolerability and Immune Responses of Ebola-S and Marburg Vaccines in Healthy Adults

NCT04723602 | Completed Phase 1 FDA Drug

• 1 other identifier: Sabin 001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective:

• To evaluate the safety and tolerability of cAd3-EBO-S and cAd3 Marburg vaccines when administered Intramuscular (IM) at a dose of 1 x 10\^11 particle units (PU) to healthy adults. Secondary Objectives:
• To evaluate the antibody response to Monovalent Chimpanzee Adenoviral Vectored Filovirus Ebola-S (cAd3-EBO-S) and Monovalent Chimpanzee Adenoviral Vectored Filovirus (Marburg) (cAd3 Marburg) vaccines as assessed by antigen glycoprotein (GP) specific (enzyme-linked immunosorbent assay) ELISA
• To collect sufficient post-vaccination plasma to support further development of filovirus assays

Conditions

Ebola Virus Disease; Marburg Virus Disease

Keywords

Coronavirus Disease; Creatine phosphokinase; Clinical Research Associate; Contract Research Organization; Division of AIDS; Disseminated Intravascular Coagulation; Diagnostic Lab of Oklahoma; Deoxyribonucleic Acid; Species Zaire Ebolavirus; Electronic Case Report Form; Ethylenediaminetetraacetic Acid; Ebola Hemorrhagic Fever; Enzyme-Linked Immunosorbent Assay; Food and Drug Administration; Ebola Virus Disease; Degrees Fahrenheit; Good Clinical Practices; Good Laboratory Practices; Grams; Glycoprotein; Government and Public Health Solutions; GlaxoSmithKline; Hemagglutinin; Hereditary Angioedema; Hepatitis B Virus; Hepatitis C Virus; Human immunodeficiency virus; Human T-cell Leukemia Lymphoma Virus; Investigator's Brochure; International Council for Harmonisation; International Committee on the Taxonomy of Viruses; Identification; Immunoglobulin G; Immunoglobulin M; Intramuscular(ly); Investigational New Drug; Investigational product; Intravenous; Marburg Virus; Marburg Virus Disease; Marburg hemorrhagic fever; Milliliter; Millimeters of Mercury; Modified Vaccinia Ankara; Nucleic Acid Test; Non-Disclosure Agreement; Non-Human Primate; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Nucleoprotein; Nonsteroidal Anti-Inflammatory Drug; Oklahoma Blood Institute; Office for Human Research Protection; Plasmapheresis Assessment Review Team; Plaque Forming Unit; Physical Exam; Principal Investigator; Post Injection Reactogenicity; Project Manager; Prothrombin Time; Partial Thromboplastin Time; Particle Units; Ravn Virus; Recombinant Human Adenovirus Serotype 5; Species Reston ebolavirus; Ribonucleic Acid; Rapid Plasma Regain; Reverse Transcription Polymerase Chain Reaction; Serious Adverse Event; Severe Acute Respiratory Syndrome Coronavirus 2; Statistical Analysis System; Schedule of Events; Standard Operating Procedure; Serum Separator Tube; Species Sudan Ebolavirus; Suspected, Unexpected and Serious Adverse Reaction; Species Taï Forest Ebolavirus; Technical Resources International, Inc; Universal Donor History Questionnaire; Upper Limit of Normal; Viral Particles; Vaccine Research Center; Vesicular Stomatitis Virus; Variant Creutzfeldt-Jakob Disease; White blood cell; World Health Organization; Western Institutional Review Board; Wild type; Zaire Ebola virus; Acquired Angioedema; Program, Inc.; Human adenovirus Serotype 5; Activities of Daily Living; Adverse Event; Acquired Immunodeficiency Syndrome; Alanine aminotransferase; Assessment of Understanding; Aspartate Aminotransferase; Biomedical Advanced Research and Development Authority; Species Bundibugyo ebolavirus; Blood Establishment Computer System; Body mass index; Blood Urea Nitrogen; Recombinant Chimpanzee Adenovirus Serotype 3; Recombinant Chimpanzee Adenovirus; Recombinant Chimpanzee Adenovirus Serotype 63; Complete blood count; Center for Disease Control and Prevention; Code of Federal Regulations; Confidence Interval; Centimeters; Type 3-Vectored Ebola virus Vaccine; Type 3-Vectored Ebola Sudan Vaccine; Type 3-Vectored Marburg Vaccine

Outcome Measures

Primary Outcomes (7)

• Safety of Ebola and Marburg vaccines assessed by clinical observation.

  Safety of Ebola and Marburg vaccines, as seen in local reactogenicity signs and symptoms with diary questionnaire card.

  7 Days

• Safety of Ebola and Marburg vaccines assessed by clinical observation.

  Safety of Ebola and Marburg vaccines, as seen in systemic reactogenicity signs and symptoms with diary questionnaire card.

  7 Days

• Safety of Ebola and Marburg vaccines assessed by change from baseline in levels of Complete Blood Count (CBC).

  Safety of Ebola and Marburg vaccines assessed by change in levels of Complete Blood Count (CBC) w/differential count as laboratory measures of safety from baseline.

  6 months

• Safety of Ebola and Marburg vaccines assessed by change from baseline in levels of Creatinine.

  Safety of Ebola and Marburg vaccines assessed by change in levels of Creatinine as laboratory measures of safety from baseline.

  6 months

• Safety of Ebola and Marburg vaccines assessed by change from baseline in levels of Alanine Transaminase (ALT).

  Safety of Ebola and Marburg vaccines assessed by change in levels of Alanine Transaminase (ALT) as laboratory measures of safety from baseline.

  6 months

• Safety of Ebola and Marburg vaccines assessed by adverse experiences.

  Safety of Ebola and Marburg vaccines assessed by adverse events of all severities (Mild, moderate, and severe)

  28 days

• Safety of Ebola and Marburg vaccines assessed by serious adverse experiences.

  Safety of Ebola and Marburg vaccines assessed by serious adverse events of all severities (Mild, moderate, and severe)

  6 months

Secondary Outcomes (2)

• Evaluation of antibody response to cAd3-EBO-S and cAd3 Marburg vaccines

  Measured at Day 1, 15, 22, 29, 36, 43, 50, 57, and 64

• Collection of sufficient post-vaccination plasma to support further development of filovirus assays.

  May be collected at Day 29, 36, 43, 50, 57 and/or 64

Study Arms (2)

cAd3-Marburg at 1 x 10^11 Particle Units (PU)

ACTIVE COMPARATOR

A total of 16 healthy adults will be enrolled and vaccinated with a single dose of vaccine. Group 1 (N = 16) will receive a single injection of cAd3-Marburg at 1 x 10\^11 Particle Units (PU) vaccine.

Biological: cAd3-Marburg

cAd3-EBO-S at 1 x 10^11 PU vaccine

ACTIVE COMPARATOR

A total of 16 healthy adults will be enrolled and vaccinated with a single dose of vaccine. Group 2 (N = 16) will receive a single injection of cAd3-EBO-S at 1 x 10\^11 Particle Units (PU) vaccine.

Biological: cAd3-EBO-S

Interventions

cAd3-Marburg BIOLOGICAL

A total of 16 healthy adults will be enrolled and vaccinated with a single dose of vaccine. Group 1 (N = 16) will receive a single injection of cAd3-Marburg at 1 x 10\^11 Particle Units (PU) vaccine.

cAd3-Marburg at 1 x 10^11 Particle Units (PU)

cAd3-EBO-S BIOLOGICAL

A total of 16 healthy adults will be enrolled and vaccinated with a single dose of vaccine. Group 2 (N = 16) will receive a single injection of cAd3-EBO-S at 1 x 10\^11 Particle Units (PU) vaccine.

cAd3-EBO-S at 1 x 10^11 PU vaccine

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female participant must be between 18-50 (inclusive) years of age;
• Meet criteria for plasma donation\*;
• Available for clinic follow-up through Day 99 and one additional follow-up call on Day 181 (±14 days);
• Agrees not to receive any vaccine from day of enrollment through Day 99;
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process;
• Agree to have photos taken of the vaccination site, if indicated ;
• Willing to complete repeated plasmapheresis and other protocol requirements;
• Must complete an Assessment of Understanding (AoU) by answering 9 out of 10 questions correctly at least once in 3 attempts;
• Willing to donate blood for sample storage and future unspecified assay development;
• Able to read (English) and willing to complete informed consent process;
• In good general health without clinically significant medical history, based on medical history, physical examination, vital signs and clinical laboratory results;
• Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) ≥ 17 and ≤ 35 within the 28 days prior to vaccination;
• Laboratory Criteria within 28 days prior to vaccination (normal per testing laboratory) for: complete blood count (CBC) with differential count, alanine aminotransferase (ALT), serum creatinine and total protein;
• Serology screen negative for infectious diseases (hepatitis B, hepatitis C, HIV, HTLV (Human T-cell leukemia lymphoma virus), Chagas disease, Syphilis;
• Nucleic acid test (NAT) negative for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), West Nile and Zika;

You may not qualify if:

• Investigational COVID-19, Ebola or Marburg vaccine in a prior clinical trial or prior receipt of a cAd3 adenoviral vectored investigational vaccine;
• Use of immunomodulators and systemic glucocorticoids in daily doses of glucocorticoid equivalence \> 20 mg of prednisolone in the last 90 days and for periods exceeding 10 days. Non-steroidal anti-inflammatory drugs \[NSAIDS\] are permitted. Participants that have used less than the stated glucocorticoid dose may still be excluded at the Investigator's discretion;
• Blood products within 112 days prior to enrollment;
• Investigational research agents within 90 days prior to enrollment;
• Any licensed vaccine, inclusive of "live-attenuated" vaccine (e.g., oral polio, yellow fever, measles, etc.), killed, or subunit vaccine, within 28 days prior to enrollment;
• Any experimental vaccines within 6 months prior to enrollment;
• Current anti-tuberculosis prophylaxis or therapy;
• Female participant specific criteria: woman who is pregnant, breast-feeding or planning to become pregnant through Day 181 (±14 days);
• Unsatisfactory vein assessment for plasmapheresis via peripheral access (more details in Section 5.2.1)
• History of any of the following clinically significant conditions:
• Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain;
• Allergic reaction to excipients in the study vaccine including gentamycin, neomycin or streptomycin;
• Clinically significant autoimmune disease or immunodeficiency;
• Asthma that is not well controlled;
• Positive result on a rapid plasma regain (RPR) test (A blood test for Syphilis);

Sponsors & Collaborators

• Albert B. Sabin Vaccine Institute: lead
• ICON plc: collaborator
• Oklahoma Blood Institute: collaborator

Study Sites (1)

Oklahoma Blood Institute (OBI)

Oklahoma City, Oklahoma, 73104, United States

Location

Related Publications (5)

• Sanchez A, Kiley MP, Klenk HD, Feldmann H. Sequence analysis of the Marburg virus nucleoprotein gene: comparison to Ebola virus and other non-segmented negative-strand RNA viruses. J Gen Virol. 1992 Feb;73 ( Pt 2):347-57. doi: 10.1099/0022-1317-73-2-347.

  PMID: 1538192 RESULT

• Sanchez A, Kiley MP, Holloway BP, Auperin DD. Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res. 1993 Sep;29(3):215-40. doi: 10.1016/0168-1702(93)90063-s.

  PMID: 8237108 RESULT

• Geisbert TW, Jahrling PB. Exotic emerging viral diseases: progress and challenges. Nat Med. 2004 Dec;10(12 Suppl):S110-21. doi: 10.1038/nm1142.

  PMID: 15577929 RESULT

• Hensley LE, Jones SM, Feldmann H, Jahrling PB, Geisbert TW. Ebola and Marburg viruses: pathogenesis and development of countermeasures. Curr Mol Med. 2005 Dec;5(8):761-72. doi: 10.2174/156652405774962344.

  PMID: 16375711 RESULT

• Ledgerwood JE, DeZure AD, Stanley DA, Coates EE, Novik L, Enama ME, Berkowitz NM, Hu Z, Joshi G, Ploquin A, Sitar S, Gordon IJ, Plummer SA, Holman LA, Hendel CS, Yamshchikov G, Roman F, Nicosia A, Colloca S, Cortese R, Bailer RT, Schwartz RM, Roederer M, Mascola JR, Koup RA, Sullivan NJ, Graham BS; VRC 207 Study Team. Chimpanzee Adenovirus Vector Ebola Vaccine. N Engl J Med. 2017 Mar 9;376(10):928-938. doi: 10.1056/NEJMoa1410863. Epub 2014 Nov 26.

  PMID: 25426834 RESULT

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola; Marburg Virus Disease; Disseminated Intravascular Coagulation; Angioedemas, Hereditary; Hepatitis B; Hepatitis C; Acquired Immunodeficiency Syndrome; Communicable Diseases; Creutzfeldt-Jakob Syndrome; Acquired angioedema

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections; Monkey Diseases; Primate Diseases; Animal Diseases; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Thrombophilia; Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes; Blood-Borne Infections; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Flaviviridae Infections; HIV Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Prion Diseases; Central Nervous System Infections; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Roxana Rustomjee, MBChB

  The Albert B. Sabin Vaccine Institute

  STUDY CHAIR

• Michael Stevenson, MD

  Oklahoma Blood Institute

  PRINCIPAL INVESTIGATOR

• David Hoover, MD

  ICON plc

  STUDY DIRECTOR

• Tuan Le, MD

  Oklahoma Blood Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2 cohorts of 16 participants each.

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: January 26, 2021
• Study Start: January 6, 2021
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2021
• Last Updated: August 3, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)