Clinical trial NCT04723602: Evaluation of Safety, Tolerability and Immune Responses of Ebola-S and Marburg Vaccines in Healthy Adults
Official title: Phase 1b Trial to Evaluate Safety, Tolerability and Immune Responses of 2 Monovalent Chimpanzee Adenoviral Vectored Filovirus (Ebola-S and Marburg) Vaccines to Healthy Adults, Collection of Plasma/Serum for the Purposes of Assay Development
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Albert B. Sabin Vaccine Institute
Sponsor class: OTHER
Collaborators: name: ICON plc
name: Oklahoma Blood Institute
First posted: 2021-01-26
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 cohorts of 16 participants each.
Primary purpose: PREVENTION

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

Detailed description: Primary Endpoints: Safety

Assessment of product safety will include clinical observation and monitoring of clinical chemistry and hematology parameters. Safety will be closely monitored after injection and evaluated through Day 99 and one additional safety follow-up telephone call on Day 181 (± 14 Days). The following parameters will be assessed:

* Occurrence and severity of solicited local reactogenicity signs and symptoms for 7 days following the vaccination
* Occurrence and severity of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination
* Change from baseline for safety laboratory measures
* Occurrence of adverse events of all severities through 28 days after vaccination
* Occurrence of serious adverse events and new chronic medical conditions through the last safety follow up call at Day 181(± 14 days)

Secondary Endpoints :

* Antibody levels against vaccines cAd3-EBO-S and cAd3 Marburg as measured by enzyme-linked immunosorbent assay (ELISA) on Day 1, 15, 22, 29, 36, 43, 50, 57 and 64
* 20 Liters of plasma per vaccine group will be collected for the purpose of assay development

Eligibility criteria: Inclusion Criteria:

* 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;
* Negative antibody and reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome Covid 2 (SARS CoV-2) and free of current or prior symptoms concerning for COVID-19. Participants with a previous positive RT-PCR, at least 90 days prior to screening as reported in medical history, will not be excluded if they are antibody negative;
* Female participant specific criteria:

  * Negative pregnancy serum test at screening and, negative urine pregnancy test before vaccination unless one of the following criteria is met:
* At least 1 year post-menopausal;
* Surgically sterile;

  * Use of oral, implantable, transdermal or injectable contraceptives for 21 days prior to and agrees to use through Day 181 ;
  * Use of another reliable form of contraception must be approved by the Investigator (e.g., double barrier method, Depo-Provera, intrauterine device, Norplant, oral contraceptives, contraceptive patches);
* Male participants must agree:

  * Not to father a child or donate sperm through Day 181;
  * To use an effective means of birth control from at least 21 days prior to enrollment through Day 181 if assessed to be of reproductive potential.

Meet the criteria described in the AABB (formerly known as American Association of Blood Bank) and Uniform Donor History Questionnaire, with the exception of travel for malaria or Variant Creutzfeldt-Jakob Disease (vCJD) risk

Exclusion Criteria:

* 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);
  * Diabetes mellitus Type I or II;
  * Thyroid disease that is not well controlled ;
  * A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema;
  * Idiopathic urticaria within the last 1 year;
  * Hypertension that is not well controlled;
  * Bleeding disorder diagnosed by a doctor or use of anticoagulant medications such as, Coumadin, Eliquis, Pradaxa (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws;
  * A malignancy that is active, currently being treated, or not surgically cured (breast or prostate cancer successfully treated, with or without surgery is excluded; if diagnosed malignancy is 5 or more years prior to enrollment and cured with no ongoing treatment it will NOT be considered an exclusion);
  * Seizure in the past 3 years or treatment for seizure disorder in the past 3 years;
  * Asplenia or functional asplenia;
  * Psychiatric condition that precludes compliance with the protocol; past or present psychoses; or within five years prior to enrollment, history of a suicide plan or attempt;
  * Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent.
  * Abnormal laboratory results (per testing laboratory)
  * Positive COVID-19 symptom screen, SARS-CoV-2 RT-PCR, or SARS CoV-2 antibody test

Primary outcomes:
measure: Safety of Ebola and Marburg vaccines assessed by clinical observation.
timeFrame: 7 Days
measure: Safety of Ebola and Marburg vaccines assessed by clinical observation.
timeFrame: 7 Days
measure: Safety of Ebola and Marburg vaccines assessed by change from baseline in levels of Complete Blood Count (CBC).
timeFrame: 6 months
measure: Safety of Ebola and Marburg vaccines assessed by change from baseline in levels of Creatinine.
timeFrame: 6 months
measure: Safety of Ebola and Marburg vaccines assessed by change from baseline in levels of Alanine Transaminase (ALT).
timeFrame: 6 months
measure: Safety of Ebola and Marburg vaccines assessed by adverse experiences.
timeFrame: 28 days
measure: Safety of Ebola and Marburg vaccines assessed by serious adverse experiences.
timeFrame: 6 months
Secondary outcomes:
measure: Evaluation of antibody response to cAd3-EBO-S and cAd3 Marburg vaccines
timeFrame: Measured at Day 1, 15, 22, 29, 36, 43, 50, 57, and 64
measure: Collection of sufficient post-vaccination plasma to support further development of filovirus assays.
timeFrame: May be collected at Day 29, 36, 43, 50, 57 and/or 64
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: Oklahoma Blood Institute (OBI)
state: Oklahoma
Study officials:
affiliation: The Albert B. Sabin Vaccine Institute
name: Roxana Rustomjee, MBChB
role: STUDY_CHAIR
affiliation: Oklahoma Blood Institute
name: Michael Stevenson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ICON plc
name: David Hoover, MD
role: STUDY_DIRECTOR
affiliation: Oklahoma Blood Institute
name: Tuan Le, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: Geisbert TW, Jahrling PB. Exotic emerging viral diseases: progress and challenges. Nat Med. 2004 Dec;10(12 Suppl):S110-21. doi: 10.1038/nm1142.
citation: 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.
citation: 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.