Ebola Sudan Chimpanzee Adenovirus Vector Vaccine in Healthy Adults

• ClinicalTrials.gov Identifier: NCT04041570
• Recruitment Status: Completed
• First Posted: August 1, 2019
• Last Update Posted: September 16, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: US Military HIV Research Program
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

This is a Phase I, open-label study to examine safety, tolerability and immunogenicity of an investigational Ebola vaccine given by intramuscular (IM) injection to healthy adults. The study is a dose escalation of VRC-EBOADC086-00-VP, a chimpanzee adenovirus serotype 3 vector vaccine, which encodes wild type (WT) glycoprotein (GP) from the Sudan strain of Ebolavirus.

Condition or disease	Intervention/treatment	Phase
Ebola Virus	Biological: cAd3-EBO S vaccine	Phase 1

Detailed Description:

It is anticipated that about 100 volunteers will be screened in order to enroll a total of 40 participants. The 40 participants will be evenly split, with 20 in each of the two dosage groups for cAd3-EBO S. The dose escalation plan includes daily review of any new safety data by a study clinician, regular review of safety data by the protocol team and a staged enrollment plan with required interim safety reviews. The study will begin with enrollment of 3 participants into Group 1 at a rate of 1 participant per day. After at least 7 days of follow-up for the first 3 vaccinated participants, an interim safety review will occur before enrollment of additional participants into the group. If no safety issues are identified, an additional 17 participants will be enrolled to complete Group 1. When there is a minimum of seven days of follow-up safety data from the last enrolled participant in Group 1, an interim safety review will occur. Once no safety issues are identified, enrollment of participants into the next dose level (Group 2) will begin with the enrollment of 3 participants at a rate of 1 participant per day. After at least 7 days of followup for the first 3 vaccinated participants in Group 2, an interim safety review will occur before the enrollment of additional participants into Group 2. If no safety issues are identified, an additional 17 participants will be enrolled to complete Group 2.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Sequential Assignment Dose Escalation
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee Adenovirus Vector Vaccine, VRC-EBOADC086-00-VP (cAd3- EBO S), in Healthy Adults
• Actual Study Start Date: July 2, 2019
• Actual Primary Completion Date: September 7, 2020
• Actual Study Completion Date: September 7, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: cAd3-EBO S at 1x10^10 PU dose; Twenty (20) subjects enrolled in Group 1 will receive a 1x10^10 PU dose of cAd3-EBO S vaccine administered intramuscular (IM) with needle and syringe in a volume of 1 mL.	Biological: cAd3-EBO S vaccine; The recombinant chimpanzee adenovirus Type 3-vectored Ebola vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S) is composed of a cAd3 vector that expresses Ebola Sudan wild type glycoprotein (WT GP).; Other Name: • VRC-EBOADC086-00-VP
Experimental: cAd3-EBO S at 1x10^11 PU dose; Twenty (20) subjects enrolled in Group 2 will receive a 1x10^11 PU dose of cAd3-EBO S vaccine administered intramuscular (IM) with needle and syringe in a volume of 1 mL.	Biological: cAd3-EBO S vaccine; The recombinant chimpanzee adenovirus Type 3-vectored Ebola vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S) is composed of a cAd3 vector that expresses Ebola Sudan wild type glycoprotein (WT GP).; Other Name: • VRC-EBOADC086-00-VP

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects Experiencing Local Reactogenicity Symptoms Following a Dose of 1 x 10^10 PU [ Time Frame: Over 7 days after vaccine administration ]
   Solicited local reactogenicity (e.g., injection-site swelling, redness, and pain) will be recorded in the clinic at a minimum of 30 minutes post injection and then by the participant for 7 days using a diary card.
2. Number of Subjects Experiencing Systemic Reactogenicity Symptoms Following a Dose of 1 x 10^10 PU [ Time Frame: Over 7 days after vaccine administration ]
   Temperature and solicited systemic signs/symptoms will be recorded in the clinic prior to vaccination and at a minimum of 30 minutes post injection and then daily by the participant for 7 days using a diary card. Symptoms monitored include, for example, fever, joint pain, malaise (feeling unwell), myalgias (muscles aches other than at injection site), headache, chills, nausea, and pain at injection site.
3. Number of Subjects Reporting an Adverse Event Following a Dose of 1 x 10^10 PU [ Time Frame: Over 28 days after vaccine administration ]
   Recording of all AEs will occur during the period from study agent administration through 28 days after study agent administration. Solicited AEs will be recorded in the study database for 7 days after injection without the collection of attribute assessments. All unsolicited AEs and SAEs that occur during the period from study agent administration through 28 days after study agent administration will be recorded in the study database. After study day 28, only SAEs and new chronic medical conditions that require ongoing medical management will be recorded as AEs in the study database.
4. Number of Subjects Reporting a Serious Adverse Event Following a Dose of 1 x 10^10 PU [ Time Frame: Over 48 weeks after vaccine administration ]

   Recording of all AEs will occur during the period from study agent administration through 28 days after study agent administration. Solicited AEs will be recorded in the study database for 7 days after injection without the collection of attribute assessments. All unsolicited AEs and SAEs that occur during the period from study agent administration through 28 days after study agent administration will be recorded in the study database. After study day 28, only SAEs and new chronic medical conditions that require ongoing medical management will be recorded as AEs in the study database.

   The FDA Guidance for Industry (September 2007): "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" is the basis for the severity grading of adverse events in this protocol. Some modifications to the grading scales were made, as described in the clinical protocol.

5. Number of Subjects Experiencing Local Reactogenicity Symptoms Following a Dose of 1 x 10^11 PU [ Time Frame: Over 7 days after vaccine administration ]
   Solicited local reactogenicity (e.g., injection-site swelling and redness) will be recorded in the clinic at a minimum of 30 minutes post injection and then by the participant for 7 days using a diary card.
6. Number of Subjects Experiencing Systemic Reactogenicity Symptoms Following a Dose of 1 x 10^11 PU [ Time Frame: Over 7 days after vaccine administration ]
   Temperature and solicited systemic signs/symptoms will be recorded in the clinic prior to vaccination and at a minimum of 30 minutes post injection and then daily by the participant for 7 days using a diary card. Symptoms monitored include, for example, fever, joint pain, malaise (feeling unwell), myalgias (muscles aches other than at injection site), headache, chills, nausea, and pain at injection site.
7. Number of Subjects Reporting an Adverse Event Following a Dose of 1 x 10^11 PU [ Time Frame: Over 28 days after vaccine administration ]
   Recording of all AEs will occur during the period from study agent administration through 28 days after study agent administration. Solicited AEs will be recorded in the study database for 7 days after injection without the collection of attribute assessments. All unsolicited AEs and SAEs that occur during the period from study agent administration through 28 days after study agent administration will be recorded in the study database. After study day 28, only SAEs and new chronic medical conditions that require ongoing medical management will be recorded as AEs in the study database.
8. Number of Subjects Reporting a Serious Adverse Event Following a Dose of 1 x 10^11 PU [ Time Frame: Over 48 weeks after vaccine administration ]

   Recording of all AEs will occur during the period from study agent administration through 28 days after study agent administration. Solicited AEs will be recorded in the study database for 7 days after injection without the collection of attribute assessments. All unsolicited AEs and SAEs that occur during the period from study agent administration through 28 days after study agent administration will be recorded in the study database. After study day 28, only SAEs and new chronic medical conditions that require ongoing medical management will be recorded as AEs in the study database.

   The FDA Guidance for Industry (September 2007): "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" is the basis for the severity grading of adverse events in this protocol. Some modifications to the grading scales were made, as described in the clinical protocol.

Secondary Outcome Measures :

1. Number of Vaccinated Subjects Showing a Positive Response to Ebola GP [ Time Frame: 4 weeks after vaccination ]
   Humoral immune response to the GP insert in VRCEBOADC086-00-VP, assessed by ELISA
2. Number of Vaccinated Subjects Showing an Increase in the Presence of cAd3 Neutralizing Antibody [ Time Frame: 4 weeks after vaccination ]
   The pre-existing and post-vaccination presence of cAd3 neutralizing antibody is evaluated by vector-specific neutralization assays
3. Number of Vaccinated Subjects Showing a Positive Response to Ebola GP by intracellular cytokine staining (ICS) [ Time Frame: 4 weeks after vaccination ]
   Quantitates the cellular immune response to Ebola GP antigens

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. 18 to 50 years old.
2. Available for clinical follow-up through Week 48 after enrollment.
3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
4. Able and willing to provide fingerprints and have their photographs taken including injection site photographs.
5. Must allow home visits
6. Must complete an Assessment of Understanding (AoU) prior to enrollment by answering 9 out of 10 questions at least once in 3 attempts.
7. Able to read (English or Luganda) and willing to complete the informed consent process.
8. In good general health without clinically significant medical history.

9. Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) ≤ 40 within the 56 days prior to enrollment.

   Laboratory Criteria within 56 days prior to enrollment:

10. Hemoglobin ≥ 11.0 g/dL for women; ≥12.5 g/dL for men.
11. White blood cells (WBC) = 2,500-12,000 cells/mm3.
12. Total lymphocyte count ≥ 800 cells/mm3.
13. Platelets = 125,000 - 400,000/mm3.
14. Alanine aminotransferase (ALT) ≤ 1.25 x upper limit of normal.
15. Serum creatinine ≤ 1 x upper limit of normal.

16. HIV-uninfected as evidenced by a negative FDA-approved HIV diagnostic test.

    Female-Specific Criteria:

17. Negative β-HCG (human chorionic gonadotropin) pregnancy test; serum β-HCG at screening and urine β-HCG at enrollment if woman is of reproductive potential.
18. Agrees to use an effective means of birth control from at least 21 days prior to enrollment through 24 weeks after study vaccination if assessed to be of reproductive potential.

Exclusion Criteria:

Volunteer has received any of the following substances:

1. Investigational Ebola or Marburg vaccine in a prior clinical trial or prior receipt of a cAd3 adenoviral vectored investigational vaccine.
2. Chronic use of immunomodulators and systemic glucocorticoids in daily doses of glucocorticoid equivalence > 20 mg of prednisolone, 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.
3. Blood products within 112 days (16 weeks) prior to enrollment.
4. Investigational research agents within 28 days (4 weeks) prior to enrollment.
5. Live attenuated vaccines within 28 days (4 weeks) prior to enrollment.
6. Subunit or killed vaccines within 14 days (2 weeks) prior to enrollment.

7. Current anti-tuberculosis prophylaxis or therapy.

   Female-specific criteria:

8. Woman who is pregnant, breast-feeding or planning to become pregnant during the first 24 weeks after study vaccine administration.

   Volunteer has a history of any of the following clinically significant conditions:

9. Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain.
10. Allergic reaction to excipients in the study vaccine including gentamycin, neomycin or streptomycin.
11. Clinically significant autoimmune disease or immunodeficiency.
12. Asthma that is not well controlled.
13. Positive result on an RPR test.
14. Diabetes mellitus (type I or II).
15. Thyroid disease that is not well controlled.
16. A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema.
17. Idiopathic urticaria within the last 1 year.
18. Hypertension that is not well controlled.
19. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.
20. A malignancy that is active, currently being treated, or not surgically cured.
21. Seizure in the past 3 years or treatment for seizure disorder in the past 3 years.
22. Asplenia or functional asplenia.
23. 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.
24. 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 volunteer's ability to give informed consent.

Contacts and Locations

Locations

Uganda

Makerere University-Walter Reed Project

Kampala, Uganda

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

US Military HIV Research Program

More Information

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT04041570
• Other Study ID Numbers: RV 508; WRAIR 2439 ( Other Identifier: WRAIR )
• First Posted: August 1, 2019
• Last Update Posted: September 16, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Ebola virus; Ebola vaccine; cAd3-EBO S

Additional relevant MeSH terms:

Hemorrhagic Fever, Ebola; Virus Diseases; Hemorrhagic Fevers, Viral; RNA Virus Infections; Filoviridae Infections; Mononegavirales Infections