cAd3-Marburg Vaccine in Healthy Adults

NCT03475056 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: RV 507WRAIR #2438
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

RV 507 was a Phase I, open-label study to examine the safety, tolerability and immunogenicity of an investigational Marburg vaccine given by intramuscular (IM) injection to healthy adults. The study was a dose escalation of VRC-MARADC087-00-VP, a chimpanzee adenovirus serotype 3 (cAd3) vector vaccine, which encodes wild type (WT) glycoprotein (GP) from Marburgvirus.

Conditions

Marburg Virus Disease

Keywords

Marburg virus; Marburg vaccine; cAd3-Marburg vaccine

Outcome Measures

Primary Outcomes (6)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-Marburg 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 (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-Marburg 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 (FDA Guidance - September 2007).The Division of AIDS AE Grading Table Corrected (Version 2.1-July 2017) 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-Marburg 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 FDA Guidance, September 2007 were used.

  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 (6)

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

  Through 28 days after study product administration

• Mean Titers of Antibodies to the Human Adenovirus Serotype 5 (Ad5) Vector at 28 Days After the cAd3-Marburg Vaccine Administration

  Through 28 days after study product administration

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

  Through 28 days after study product administration

• Magnitude of Marburg-Specific Antibody Responses After the cAd3-Marburg Vaccine Administration

  Through 28 days after study product administration

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

  Through 28 days after study product administration

Study Arms (2)

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

EXPERIMENTAL

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

Biological: cAd3-Marburg vaccine

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

EXPERIMENTAL

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

Biological: cAd3-Marburg vaccine

Interventions

cAd3-Marburg vaccine BIOLOGICAL

The recombinant chimpanzee adenovirus Type 3-vectored Marburg vaccine, VRC-MARADC087-00-VP (cAd3-Marburg) is composed of a cAd3 vector that expresses Marburg wild type glycoprotein (WT GP).

Also known as: VRC-MARADC087-00-VP

Group 1: cAd3-Marburg vaccine (1x10^10 PU); Group 2: cAd3-Marburg 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. Proof of identity includes a valid U.S. government-issued or state-issued photo identification (ID) such as a driver's license, military ID, or U.S. passport.
• Able and willing to provide a personal mobile phone number or home phone number at which the participant can be reliably contacted. Participants will be contacted primarily for study visit 2A (Appendix 1), as a reminder of an upcoming visit, and after missed visits for rescheduling purposes.
• Able and willing to complete the informed consent process and demonstrate understanding with a passing score (90% or greater) on the Assessment of Understanding (AOU) by the third attempt.
• 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 ≥ 11.5 g/dL for women; ≥13.0 g/dL for men.
• White blood cells (WBC) = 3,300-12,000 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.
• Serum creatinine ≤ 1 x upper limit of normal.
• HIV-uninfected as evidenced by a negative FDA-approved HIV diagnostic blood test.

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 vectored investigational vaccine.
• Immunosuppressive medications within 2 weeks prior to enrollment.
• 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)

WRAIR Clinical Trials Center,

Silver Spring, Maryland, 20910, United States

Location

Related Publications (5)

• 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

• Hamer MJ, Houser KV, Hofstetter AR, Ortega-Villa AM, Lee C, Preston A, Augustine B, Andrews C, Yamshchikov GV, Hickman S, Schech S, Hutter JN, Scott PT, Waterman PE, Amare MF, Kioko V, Storme C, Modjarrad K, McCauley MD, Robb ML, Gaudinski MR, Gordon IJ, Holman LA, Widge AT, Strom L, Happe M, Cox JH, Vazquez S, Stanley DA, Murray T, Dulan CNM, Hunegnaw R, Narpala SR, Swanson PA 2nd, Basappa M, Thillainathan J, Padilla M, Flach B, O'Connell S, Trofymenko O, Morgan P, Coates EE, Gall JG, McDermott AB, Koup RA, Mascola JR, Ploquin A, Sullivan NJ, Ake JA, Ledgerwood JE; RV 507 Study Team. Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial. Lancet. 2023 Jan 28;401(10373):294-302. doi: 10.1016/S0140-6736(22)02400-X.

  PMID: 36709074 DERIVED

MeSH Terms

Conditions

Marburg Virus Disease

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections; Monkey Diseases; Primate Diseases; Animal Diseases

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

Study Officials

• Melinda Hamer, M.D.

  WRAIR Clinical Trials Center

  PRINCIPAL INVESTIGATOR

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: Dose escalation

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 23, 2018
• Study Start: October 9, 2018
• Primary Completion: December 19, 2019
• Study Completion: December 19, 2019
• Last Updated: August 11, 2022
• Results First Posted: January 14, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)