Marburg Virus DiseasePhase 1NCT03475056
cAd3-Marburg Vaccine in Healthy Adults
A Phase 1 study testing cAd3-Marburg vaccine in people with Marburg Virus Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Marburg Virus Disease
- What is being tested?
- cAd3-Marburg vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Oct 2018to 19 Dec 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18 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.
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- 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.
- Female-Specific Criteria:
- Negative β-HCG (human chorionic gonadotropin) pregnancy test; serum β-HCG at screening (or urine if screening is the same day as enrollment) and urine β-HCG at enrollment if woman is of reproductive potential.
- 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.
Who cannot join
- 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.
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- 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.
- Positive syphilis serology. False-positive results will also exclude a participant.
- 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 (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular (IM) injections or blood draws.
- A malignancy that is active, currently being treated, or not surgically cured.
- 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 volunteer's ability to give informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
WRAIR Clinical Trials Center,
Silver Spring, Maryland, 20910
About this study
Official title: RV 507: A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of the Marburg Chimpanzee Adenovirus Vector Vaccine, VRC-MARADC087-00-VP (cAd3-Marburg), in Healthy Adults
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.
Read the detailed description
A total of 40 participants were evenly split, with 20 in each of the two dosage groups, to receive the investigational cAd3-Marburg vaccine at a dose of either 1x10^10 particle units (PU) (Group 1) or 1x10^11 PU (Group 2). The dose escalation plan included 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 began with enrollment of 3 participants into Group 1 (1x10^10 PU) 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 occurred before enrollment of additional participants into the group. No safety issues were identified; therefore, an additional 17 participants were enrolled to complete Group 1. When there was a minimum of seven days of follow-up safety data from the last enrolled participant in Group 1, an interim safety review occurred. Once no safety issues were identified, enrollment of participants into the next dose level began with the enrollment of 3 participants at a rate of 1 participant per day. After at least 7 days of follow-up for the first 3 vaccinated participants in Group 2 (1x10^11 PU), an interim safety review occurred before the enrollment of additional participants into Group 2. No safety issues were identified and an additional 17 participants were enrolled to complete Group 2. Participants were followed for approximately 48 weeks.
- Conditions
- Marburg Virus Disease
- Being tested
- cAd3-Marburg vaccine
- Keywords
- Marburg virus, Marburg vaccine, cAd3-Marburg vaccine
- Medical subject headings
- Marburg Virus Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cAd3-Marburg vaccineBiological
Also called VRC-MARADC087-00-VP
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).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: cAd3-Marburg vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Vaccine-induced, cAd3-specific antibody responses as measured by neutralization assay. Participant blood samples were tested for cAd3-specific neutralizing activity, prior to and following vaccination, using a luciferase reporter gene virus neutralization assay as previously described (Clin Vaccine Immunol 2014; 21:783-6, References Section).
Measured: 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
Vaccine-induced, Ad5-specific antibody responses as measured by neutralization assay. Participant blood samples were tested for Ad5-specific neutralizing activity, prior to and following vaccination, using a luciferase reporter gene virus neutralization assay as previously described (Clin Vaccine Immunol 2014; 21:783-6, References Section).
Measured: Through 28 days after study product administration
Percentage of Participants With a Positive Marburg-Specific Antibody Response After the cAd3-Marburg Vaccine Administration
A positive response occurs if there is a significant increase in the ELISA post vaccination compared to baseline. For each participant, a t-test was performed to compare the post vaccination titers versus those at baseline. A participant is defined as a positive responder if the one-sided t-test has a p-value < 0.05.
Measured: Through 28 days after study product administration
Magnitude of Marburg-Specific Antibody Responses After the cAd3-Marburg Vaccine Administration
Geometric mean titer (GMT) was calculated along with 95% confidence intervals at Week 4 for each dose group.
Measured: Through 28 days after study product administration
Percentage of Participants With Positive Marburg-specific T Cell Responses After the cAd3-Marburg Vaccine Administration
T cell response was measured by Intracellular Cytokine Staining (ICS) assays using Peripheral Blood Mononuclear Cells (PBMCs) at 4 weeks after vaccination. The percentage of participants with T cell responses with Clopper-Pearson 95% Confidence Intervals are presented. Positivity is defined as a response over calculated thresholds determined by the trial statistician.
Measured: Through 28 days after study product administration
Magnitude of Marburg-specific T Cell Responses After the cAd3-Marburg Vaccine Administration
Median and interquartile ranges presented for total cytokine responses for both CD4 and CD8 memory T cells based on a T cell response with any cytokine at Week 4 for each dose group.
Measured: Through 28 days after study product administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2018
- Study start9 Oct 2018
- Primary completion19 Dec 2019
- Study completion19 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Marburg Virus DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- US Military HIV Research Program
- Responsible party
- Sponsor
- Investigators
- Melinda Hamer, M.D., Principal investigator, WRAIR Clinical Trials Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03475056
- Sponsor's protocol ID
- RV 507
- Other IDs
- WRAIR #2438
- Status last verified
- Aug 2022
- First submitted
- 14 Mar 2018
- Last updated
- 11 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25225676Kibuuka 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.
PubMed 25540891Ledgerwood 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.
PubMed 25426834Paris 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.
PubMed 24623627Hamer 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.
PubMed 36709074
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RV 507: A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of the Marburg Chimpanzee Adenovirus Vector Vaccine, VRC-MARADC087-00-VP (cAd3-Marburg), in Healthy Adults
- ClinicalTrials.gov ID
- NCT03475056
- Acronym / sponsor ID
- RV 507
- Conditions
- Marburg Virus Disease
- Keywords
- Marburg virus, Marburg vaccine, cAd3-Marburg vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- US Military HIV Research Program
- Study start
- 9 Oct 2018 (actual)
- Primary completion
- 19 Dec 2019 (actual)
- Study completion
- 19 Dec 2019 (actual)
- First posted
- 23 Mar 2018 (actual)
- Results
- Posted 14 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A total of 40 participants were evenly split, with 20 in each of the two dosage groups, to receive the investigational cAd3-Marburg vaccine at a dose of either 1x10^10 particle units (PU) (Group 1) or 1x10^11 PU (Group 2). The dose escalation plan included 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 began with enrollment of 3 participants into Group 1 (1x10^10 PU) 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 occurred before enrollment of additional participants into the group. No safety issues were identified; therefore, an additional 17 participants were enrolled to complete Group 1. When there was a minimum of seven days of follow-up safety data from the last enrolled participant in Group 1, an interim safety review occurred. Once no safety issues were identified, enrollment of participants into the next dose level began with the enrollment of 3 participants at a rate of 1 participant per day. After at least 7 days of follow-up for the first 3 vaccinated participants in Group 2 (1x10^11 PU), an interim safety review occurred before the enrollment of additional participants into Group 2. No safety issues were identified and an additional 17 participants were enrolled to complete Group 2. Participants were followed for approximately 48 weeks.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Dose escalation
| Arm | Type | Receives |
|---|---|---|
| Group 1: cAd3-Marburg vaccine (1x10^10 PU) | Experimental | Biological: cAd3-Marburg vaccinecAd3-Marburg vaccine (1x10^10 PU) administered intramuscularly (IM) with needle and syringe in a volume of 1 mL |
| Group 2: cAd3-Marburg vaccine (1x10^11 PU) | Experimental | Biological: cAd3-Marburg vaccinecAd3-Marburg vaccine (1x10^11 PU) administered IM with needle and syringe in a volume of 1 mL |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- 18 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.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cAd3-Marburg vaccineAlso: VRC-MARADC087-00-VPThe 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). | Biological | Group 1: cAd3-Marburg vaccine (1x10^10 PU), Group 2: cAd3-Marburg vaccine (1x10^11 PU) |
Primary outcome
Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-Marburg Vaccine Administration
Time frame: 7 days after study product 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).
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After the cAd3-Marburg Vaccine Administration
Time frame: 7 days after study product 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).
Total Number of Participants Reporting Any Reactogenicity Signs and Symptoms for 7 Days After the cAd3-Marburg Vaccine Administration
Time frame: 7 days after study product administration
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration.
Number of Participants With Abnormal Laboratory Measures of Safety
Time frame: Through 48 weeks after study product administration
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.
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs)
Time frame: Through 28 days after study product administration
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.
Number of Participants With Serious Adverse Events (SAEs)
Time frame: Through 48 weeks after study product administration
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.
6 secondary outcomes
Mean Titers of Antibodies to the Recombinant Chimpanzee Adenovirus Serotype 3 (cAd3) Vector at 28 Days After the cAd3-Marburg Vaccine Administration
Time frame: 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
Time frame: Through 28 days after study product administration
Percentage of Participants With a Positive Marburg-Specific Antibody Response After the cAd3-Marburg Vaccine Administration
Time frame: Through 28 days after study product administration
Magnitude of Marburg-Specific Antibody Responses After the cAd3-Marburg Vaccine Administration
Time frame: Through 28 days after study product administration
Percentage of Participants With Positive Marburg-specific T Cell Responses After the cAd3-Marburg Vaccine Administration
Time frame: Through 28 days after study product administration
Magnitude of Marburg-specific T Cell Responses After the cAd3-Marburg Vaccine Administration
Time frame: Through 28 days after study product administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25225676Sarwar 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.
- Background: PubMed 25540891Kibuuka 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.
- Background: PubMed 25426834Ledgerwood 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.
- Background: PubMed 24623627Paris 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.
- Derived from this study: PubMed 36709074Hamer 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melinda Hamer, M.D. principal investigator
WRAIR Clinical Trials Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cAd3-Marburg vaccine in people with Marburg Virus Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-Marburg Vaccine Administration (time frame: 7 days after study product administration). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03475056, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2022.