Dose, Safety, Tolerability and Immunogenicity of a Stabilized Prefusion RSV F Subunit Protein Vaccine, VRC-RSVRGP084-00-VP (DS-Cav1), Alone or With Alum Adjuvant, in Healthy Adults
- Conditions
- Respiratory Syncytial Virus
- Interventions
- Biological: VRC-RSVRGP084-00-VPOther: Aluminum Hydroxide Suspension
- Registration Number
- NCT03049488
- Brief Summary
Background:
Respiratory Syncytial Virus (RSV) is a virus that infects the lungs and breathing passages. Healthy adults who are infected generally have mild cold symptoms for a week or two. But it can also be serious, especially for infants and older adults. It can be spread by direct or indirect contact with respiratory secretions. Researchers want to study a new vaccine to prevent RSV.
Objective:
To see if a vaccine for RSV is safe and if it causes side effects.
Eligibility:
Healthy adults 18-50 years old
Design:
Volunteers were screened in a separate screening protocol.
Subjects had 13 visits over 1 year.
Some subjects received just vaccine. Some received vaccine mixed with alum adjuvant.
All subjects received their dose by injection in the upper arm. They received up to two doses, one at the beginning of the study and another 12 weeks later.
Subjects were monitored for 1 hour after injection and called to check on their safety 1 day after.
Subjects recorded their temperature and side effects for 7 days after each vaccination.
Subjects were provided with a thermometer to measure their temperature and a ruler to measure any changes if these occurred on their skin at the injection site.
At all visits, subjects were checked for health changes or problems. They may have had blood drawn.
At some visits, subjects had samples collected from their nose and mouth.
- Detailed Description
Study Design:
This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of VRC-RSVRGP084-00-VP vaccine alone or with alum adjuvant in a 2-injection regimen. The hypotheses are that the vaccine will be safe and tolerable for human administration, and will induce detectable immune response. The primary objective is to evaluate the safety and tolerability of the investigational vaccine at 3 dose levels administered alone or with alum adjuvant in healthy adults. Secondary objectives relate to humoral and cellular immunogenicity of the investigational vaccine regimen.
Product Description:
VRC-RSVRGP084-00-VP (DS-Cav1) was developed by VRC, NIAID and is composed of the respiratory syncytial virus (RSV) fusion (F) glycoprotein ectodomain assembled as a trimer stabilized in its prefusion native conformation with a foldon trimerization domain at the C-terminus and 4 internal mutations designated DS-Cav1 (4.1DHFR_RSVAF). The sequence is based on the RSV A2 strain from subtype A. The product was provided at a concentration of 0.5 mg/mL in 3 mL glass vials filled to 1.2 mL. Adjuvant was an aluminum hydroxide suspension (alum) provided in a sterile, pyrogen-free suspension at a concentration of 5 mg/mL in 3 mL glass vials filled to 0.7 mL. The alum dose was 500 mcg and was field mixed.
Subjects:
Healthy adult subjects ages 18-50 years
Study Plan:
Subjects were randomized into DS-Cav1 or DS-Cav1 plus alum in each dose during the study. Dose continuation and dose escalation evaluations occurred to ensure the safety data support proceeding to the higher doses. Subjects were evaluated for safety and immune responses through blood and mucosal sample collection at specified timepoints throughout the study.
VRC 317 Study Schema:
* Group: 1; Subjects: 15; Dose: 50mcg; Day 0: DS-Cav1; Week 12 \[1\]: DS-Cav1
* Group: 2; Subjects: 15; Dose: 50mcg; Day 0: DS-Cav1 + alum; Week 12 \[1\]: DS-Cav1 + alum
* Group: 3; Subjects: 15; Dose: 150mcg; Day 0: DS-Cav1; Week 12 \[1\]: DS-Cav1
* Group: 4; Subjects: 15; Dose: 150mcg; Day 0: DS-Cav1 + alum; Week 12 \[1\]: DS-Cav1 + alum
* Group: 5; Subjects: 15; Dose: 500mcg; Day 0: DS-Cav;1 Week 12 \[1\]: DS-Cav1
* Group: 6; Subjects: 15; Dose: 500mcg; Day 0: DS-Cav1 + alum; Week 12 \[1\]: DS-Cav1 + alum
All DS-Cav1 vaccinations were administered with needle and syringe into the deltoid muscle.
Total Planned Subjects: 90 (Up to 100 subjects could have been enrolled if needed to evaluate safety or immunogenicity.)
• \[1\] Week 12 dose: Optional for the last 5 subjects enrolled in each group who received the Day 0 injection and any additional subjects needed to evaluate safety or immunogenicity of a single injection.
Duration:
The study schedule required 13 clinic visits and a telephone contact after each injection.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 95
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Group 5: DS-Cav1 (500 mcg) VRC-RSVRGP084-00-VP DS-Cav1 (500 mcg) administered IM by Needle/Syringe (Day 0 and Week 12\*) \*To evaluate the safety or immunogenicity of a single vaccine dose, the Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection. Group 6:DS-Cav1 (500 mcg) + alum VRC-RSVRGP084-00-VP DS-Cav1 (500 mcg) + alum administered IM by Needle/Syringe (Day 0 and Week 12\*) \*To evaluate the safety or immunogenicity of a single vaccine dose, the Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection. Group 3: DS-Cav1 (150 mcg) VRC-RSVRGP084-00-VP DS-Cav1 (150 mcg) administered IM by Needle/Syringe (Day 0 and Week 12\*) \*The Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection, and for 5 additional subjects who were enrolled to evaluate the safety or immunogenicity of a single vaccine dose. Group 4: DS-Cav1 (150 mcg) + alum VRC-RSVRGP084-00-VP DS-Cav1 (150 mcg) + alum administered IM by Needle/Syringe (Day 0 and Week 12\*) \*To evaluate the safety or immunogenicity of a single vaccine dose, the Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection. Group 4: DS-Cav1 (150 mcg) + alum Aluminum Hydroxide Suspension DS-Cav1 (150 mcg) + alum administered IM by Needle/Syringe (Day 0 and Week 12\*) \*To evaluate the safety or immunogenicity of a single vaccine dose, the Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection. Group 1: DS-Cav1 (50 mcg) VRC-RSVRGP084-00-VP DS-Cav1 (50 mcg) administered intramuscularly (IM) by Needle/Syringe (Day 0 and Week 12\*) \*To evaluate the safety or immunogenicity of a single vaccine dose, the Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection. Group 2: DS-Cav1 (50 mcg) + alum VRC-RSVRGP084-00-VP DS-Cav1 (50 mcg) + alum administered IM by Needle/Syringe (Day 0 and Week 12\*) \*To evaluate the safety or immunogenicity of a single vaccine dose, the Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection. Group 2: DS-Cav1 (50 mcg) + alum Aluminum Hydroxide Suspension DS-Cav1 (50 mcg) + alum administered IM by Needle/Syringe (Day 0 and Week 12\*) \*To evaluate the safety or immunogenicity of a single vaccine dose, the Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection. Group 6:DS-Cav1 (500 mcg) + alum Aluminum Hydroxide Suspension DS-Cav1 (500 mcg) + alum administered IM by Needle/Syringe (Day 0 and Week 12\*) \*To evaluate the safety or immunogenicity of a single vaccine dose, the Week 12 dose was optional for the last 5 subjects who enrolled in this group and received the Day 0 injection.
- Primary Outcome Measures
Name Time Method Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of the First Product Administration of DS-Cav1 Alone or With Alum Adjuvant 7 days after the first product administration (Day 7) Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after the first study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects 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 subjects 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 Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of the Second Product Administration of DS-Cav1 Alone or With Alum Adjuvant 7 days after the second product administration (Day 91) Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after the second study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects 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 subjects 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 Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration of DS-Cav1 Alone or With Alum Adjuvant 7 days after each product administration Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects 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 subjects 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 Subjects With One or More Unsolicited Non-Serious Adverse Events (AEs) Day 0 through Day 28 after product administration Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 28 days after each study product administration. At other time periods between study product administrations and when greater than 28 days after the last 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 on the basis of his or her clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of the First Product Administration of DS-Cav1 Alone or With Alum Adjuvant 7 days after the first product administration (Day 7) Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after the first study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects 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 subjects reporting any systemic 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 Subjects With Serious Adverse Events (SAEs) Day 0 through Day 308 SAEs were reported from receipt of first study product administration through the last expected study visit at Day 308. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of the Second Product Administration of DS-Cav1 Alone or With Alum Adjuvant 7 days after the second product administration (Day 91) Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after the second study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects 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 subjects reporting any systemic 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 Subjects With Abnormal Laboratory Measures of Safety Day 0 through Day 308 Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, white blood cell (WBC) and red blood cell (RBC) counts, and neutrophil, lymphocyte, monocyte, eosinophil and basophil percents and counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC) differential, platelet, creatinine and ALT results were collected at screening (≤ 56 days before enrollment), Day 0 prior to study product administration (baseline), and at Days 7, 28, 84, 91 and 112. Institutional laboratory normals 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 Subjects Who Had Respiratory Syncytial Virus (RSV) Infection Following Product Administration Day 0 through Day 308 Respiratory Syncytial Virus (RSV) cases were recorded in the study database from receipt of the first study product administration through the last study visit.
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration of DS-Cav1 Alone or With Alum Adjuvant 7 days after each product administration Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects 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 subjects reporting any systemic 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).
- Secondary Outcome Measures
Name Time Method Respiratory Syncytial Virus Subtype A (RSV A) Antigen-specific Neutralizing Antibody Geometric Mean Titers (GMTs) at 4 Weeks After the First Product Administration of DS-Cav1 Alone or With Alum Adjuvant 4 weeks after the first product administration (Week 4) Neutralizing antibody titers were determined against a reporter RSV A2 virus (RSV A), and were summarized using geometric mean 50% inhibitory concentration (IC50). Negative samples were reported and IC50 titers were calculated using half the limit of detection. Measurements were normalized to international units per milliliter.
Respiratory Syncytial Virus Subtype A (RSV A) Antigen-specific Neutralizing Antibody Geometric Mean Titers (GMTs) at 4 Weeks After the Second Product Administration of DS-Cav1 Alone or With Alum Adjuvant 4 weeks after the second product administration (Week 16) Neutralizing antibody titers were determined against a reporter RSV A2 virus (RSV A), and were summarized using geometric mean 50% inhibitory concentration (IC50). Negative samples were reported and IC50 titers were calculated using half the limit of detection. Measurements were normalized to international units per milliliter.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States