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
Condition: Respiratory Syncytial Virus
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): VRC-RSVRGP084-00-VP; Aluminum Hydroxide Suspension
Intervention type(s): Biological; Other
Intervention description(s): VRC-RSVRGP084-00-VP is an investigational respiratory syncytial virus (RSV) vaccine.; Aluminum Hydroxide Suspension, alum, is an adjuvant.
Other intervention name(s): DS-Cav1; Alum
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Immune Response; Respiratory Syncytial Virus; Vaccine-Mediated Protection; Neutralizing Antibody; Antibody Response