Ebola Sudan Chimpanzee Adenovirus Vector Vaccine in Healthy Adults

NCT04041570 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: RV 508WRAIR 2439
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

RV 508 was a Phase I, open-label, dose-escalation study to examine the safety, tolerability and immunogenicity of an investigational Ebola vaccine in healthy adults. VRC-EBOADC086-00-VP, a chimpanzee adenovirus serotype 3 vector-based Ebola vaccine, encodes wild type (WT) glycoprotein (GP) from the Sudan strain of Ebolavirus and is administered intramuscularly (IM).

Conditions

Ebola Virus

Keywords

Ebola virus; Ebola vaccine; cAd3-EBO S

Outcome Measures

Primary Outcomes (6)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.

  7 days after study product administration

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. The majority of the reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007. The Division of AIDS AE Grading Table, Corrected Version 2.1 was used to grade reported events of joint pain (arthralgia).

  7 days after study product administration

• Total Number of Participants Reporting Any Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration.

  7 days after study product administration

• Number of Participants With Abnormal Laboratory Measures of Safety

  Any abnormal laboratory results recorded as unsolicited AEs are summarized. Labs included hematology (hemoglobin, hemoglobin change from baseline, hematocrit percent, mean corpuscular volume (MCV), platelets, and white blood cell (WBC), red blood cell (RBC) and lymphocyte counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC) with total lymphocyte count results were collected at screening (≤ 56 days before enrollment), Day 0 prior to study product administration (baseline), Day 3, and Weeks 2, 4, 8 and 24. Creatinine and ALT results were collected at screening, Day 0, Day 3 and Weeks 2, 4 and 8. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials, modified from FDA Guidance-September 2007 were used. Neutrophil results were not collected in the study database but were captured in the subject's laboratory results documentation.

  Through 48 weeks after study product administration

• Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs)

  Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the study product administration through the visit scheduled for 28 days after study product administration. At other time periods greater than 28 days after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module), and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Through 28 days after study product administration

• Number of Participants With Serious Adverse Events (SAEs)

  SAEs were recorded from receipt of the study product administration through the last expected study visit at Week 48. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Through 48 weeks after study product administration

Secondary Outcomes (5)

• Geometric Mean Titers of Antibodies to the Recombinant Chimpanzee Adenovirus Serotype 3 (cAd3) Vector at 28 Days After the cAd3-EBO S Vaccine Administration

  Through 28 days after study product administration

• Percentage of Participants With a Positive Ebola-Specific Antibody Response After the cAd3-EBO S Vaccine Administration

  Through 28 days after study product administration

• Baseline-subtracted Geometric Mean Titers of cAd3-EBO S Antibodies After the cAd3-EBO S Vaccine Administration

  Through 28 days after study product administration

• Percentage of Participants With Positive Ebola-specific T Cell Responses After the cAd3-EBO S Vaccine Administration

  Through 28 days after study product administration

• Magnitude of T Cell Response as a Percentage of EBO S-specific T Cell Subset After the cAd3-EBO S Vaccine Administration

  Through 28 days after study product administration

Study Arms (2)

Group 1: cAd3-EBO S vaccine (1x10^10 PU)

EXPERIMENTAL

cAd3-EBO S vaccine (1x10\^10 PU) administered intramuscularly (IM) with needle and syringe in a volume of 1 mL

Biological: cAd3-EBO S vaccine

Group 2: cAd3-EBO S vaccine (1x10^11 PU)

EXPERIMENTAL

cAd3-EBO S vaccine (1x10\^11 PU) administered IM with needle and syringe in a volume of 1 mL

Biological: cAd3-EBO S vaccine

Interventions

cAd3-EBO S vaccine BIOLOGICAL

The recombinant chimpanzee adenovirus Type 3-vectored Ebola vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S), is composed of a cAd3 vector that encodes Ebola Sudan wild type glycoprotein (WT GP).

Also known as: VRC-EBOADC086-00-VP

Group 1: cAd3-EBO S vaccine (1x10^10 PU); Group 2: cAd3-EBO S vaccine (1x10^11 PU)

Eligibility Criteria

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

You may qualify if:

• to 50 years old.
• Available for clinical follow-up through Week 48 after enrollment.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• Able and willing to provide fingerprints and have their photographs taken including injection site photographs.
• Must allow home visits
• Must complete an Assessment of Understanding (AoU) prior to enrollment by answering 9 out of 10 questions at least once in 3 attempts.
• Able to read (English or Luganda) and willing to complete the informed consent process.
• In good general health without clinically significant medical history.
• 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:
• Hemoglobin ≥ 11.0 g/dL for women; ≥12.5 g/dL for men.
• White blood cells (WBC) = 2,500-12,000 cells/mm\^3.
• Total lymphocyte count ≥ 800 cells/mm\^3.
• Platelets = 125,000 - 400,000/mm\^3.
• Alanine aminotransferase (ALT) ≤ 1.25 x upper limit of normal.

You may not qualify if:

• Volunteer has received any of the following substances:
• Investigational Ebola or Marburg vaccine in a prior clinical trial or prior receipt of a cAd3 adenoviral vectored investigational vaccine.
• 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.
• Blood products within 112 days (16 weeks) prior to enrollment.
• Investigational research agents within 28 days (4 weeks) prior to enrollment.
• Live attenuated vaccines within 28 days (4 weeks) prior to enrollment.
• Subunit or killed vaccines within 14 days (2 weeks) prior to enrollment.
• Current anti-tuberculosis prophylaxis or therapy.
• Female-specific criteria:
• 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:
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• US Military HIV Research Program: collaborator

Study Sites (1)

Makerere University-Walter Reed Project

Kampala, Uganda

Location

Related Publications (7)

• Sarwar UN, Costner P, Enama ME, Berkowitz N, Hu Z, Hendel CS, Sitar S, Plummer S, Mulangu S, Bailer RT, Koup RA, Mascola JR, Nabel GJ, Sullivan NJ, Graham BS, Ledgerwood JE; VRC 206 Study Team. Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial. J Infect Dis. 2015 Feb 15;211(4):549-57. doi: 10.1093/infdis/jiu511. Epub 2014 Sep 14.

  PMID: 25225676 BACKGROUND

• Kibuuka H, Berkowitz NM, Millard M, Enama ME, Tindikahwa A, Sekiziyivu AB, Costner P, Sitar S, Glover D, Hu Z, Joshi G, Stanley D, Kunchai M, Eller LA, Bailer RT, Koup RA, Nabel GJ, Mascola JR, Sullivan NJ, Graham BS, Roederer M, Michael NL, Robb ML, Ledgerwood JE; RV 247 Study Team. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial. Lancet. 2015 Apr 18;385(9977):1545-54. doi: 10.1016/S0140-6736(14)62385-0. Epub 2014 Dec 23.

  PMID: 25540891 BACKGROUND

• 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 BACKGROUND

• Paris R, Kuschner RA, Binn L, Thomas SJ, Colloca S, Nicosia A, Cortese R, Bailer RT, Sullivan N, Koup RA. Adenovirus type 4 and 7 vaccination or adenovirus type 4 respiratory infection elicits minimal cross-reactive antibody responses to nonhuman adenovirus vaccine vectors. Clin Vaccine Immunol. 2014 May;21(5):783-6. doi: 10.1128/CVI.00011-14. Epub 2014 Mar 12.

  PMID: 24623627 BACKGROUND

• U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. [July 2017]. Available from: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf

  BACKGROUND

• Amai M, Nojima M, Yuki Y, Kiyono H, Nagamura F. A review of criteria strictness in "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials". Vaccine. 2023 Aug 31;41(38):5622-5629. doi: 10.1016/j.vaccine.2023.07.072. Epub 2023 Aug 1.

  PMID: 37532612 BACKGROUND

• Mwesigwa B, Houser KV, Hofstetter AR, Ortega-Villa AM, Naluyima P, Kiweewa F, Nakabuye I, Yamshchikov GV, Andrews C, O'Callahan M, Strom L, Schech S, Anne Eller L, Sondergaard EL, Scott PT, Amare MF, Modjarrad K, Wamala A, Tindikahwa A, Musingye E, Nanyondo J, Gaudinski MR, Gordon IJ, Holman LA, Saunders JG, Costner PJM, Mendoza FH, Happe M, Morgan P, Plummer SH, Hickman SP, Vazquez S, Murray T, Cordon J, Dulan CNM, Hunegnaw R, Basappa M, Padilla M, Gajjala SR, Swanson PA 2nd, Lin BC, Coates EE, Gall JG, McDermott AB, Koup RA, Mascola JR, Ploquin A, Sullivan NJ, Kibuuka H, Ake JA, Ledgerwood JE; RV 508 Study Team. Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial. Lancet Infect Dis. 2023 Dec;23(12):1408-1417. doi: 10.1016/S1473-3099(23)00344-4. Epub 2023 Aug 3.

  PMID: 37544326 DERIVED

Results Point of Contact

• Title: VRC Clinical Trials Program Leadership
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

ctpleadership@mail.nih.gov

301-451-8715

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: Sequential Assignment Dose Escalation

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: August 1, 2019
• Study Start: July 2, 2019
• Primary Completion: September 7, 2020
• Study Completion: September 7, 2020
• Last Updated: December 6, 2022
• Results First Posted: November 24, 2021

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)