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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
40
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).
WRAIR Clinical Trials Center,
Silver Spring, Maryland, United States
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).
Time frame: 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).
Time frame: 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.
Time frame: 7 days after study product administration
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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.
Time frame: 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.
Time frame: 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.
Time frame: Through 48 weeks after study product administration
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).
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
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).
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
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.
Time frame: 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.
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
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.
Time frame: 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.
Time frame: Through 28 days after study product administration