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

NCT03049488 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17005817-I-0058
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory Syncytial Virus

Keywords

Immune Response; Respiratory Syncytial Virus; Vaccine-Mediated Protection; Neutralizing Antibody; Antibody Response

Outcome Measures

Primary Outcomes (10)

• 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

  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).

  7 days after the first product administration (Day 7)

• 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

  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).

  7 days after the second product administration (Day 91)

• Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration of DS-Cav1 Alone or With Alum Adjuvant

  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).

  7 days after each product administration

• 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

  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).

  7 days after the first product administration (Day 7)

• 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

  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).

  7 days after the second product administration (Day 91)

• Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration of DS-Cav1 Alone or With Alum Adjuvant

  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).

  7 days after each product administration

• Number of Subjects With Abnormal Laboratory Measures of Safety

  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.

  Day 0 through Day 308

• Number of Subjects 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 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.

  Day 0 through Day 28 after product administration

• Number of Subjects With Serious Adverse Events (SAEs)

  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.

  Day 0 through Day 308

• Number of Subjects Who Had Respiratory Syncytial Virus (RSV) Infection Following Product Administration

  Respiratory Syncytial Virus (RSV) cases were recorded in the study database from receipt of the first study product administration through the last study visit.

  Day 0 through Day 308

Secondary Outcomes (2)

• 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)

• 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)

Study Arms (6)

Group 1: DS-Cav1 (50 mcg)

EXPERIMENTAL

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.

Biological: VRC-RSVRGP084-00-VP

Group 2: DS-Cav1 (50 mcg) + alum

EXPERIMENTAL

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.

Biological: VRC-RSVRGP084-00-VP; Other: Aluminum Hydroxide Suspension

Group 3: DS-Cav1 (150 mcg)

EXPERIMENTAL

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.

Biological: VRC-RSVRGP084-00-VP

Group 4: DS-Cav1 (150 mcg) + alum

EXPERIMENTAL

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.

Biological: VRC-RSVRGP084-00-VP; Other: Aluminum Hydroxide Suspension

Group 5: DS-Cav1 (500 mcg)

EXPERIMENTAL

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.

Biological: VRC-RSVRGP084-00-VP

Group 6:DS-Cav1 (500 mcg) + alum

EXPERIMENTAL

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.

Biological: VRC-RSVRGP084-00-VP; Other: Aluminum Hydroxide Suspension

Interventions

Aluminum Hydroxide Suspension OTHER

Aluminum Hydroxide Suspension, alum, is an adjuvant.

Also known as: Alum

Group 2: DS-Cav1 (50 mcg) + alum; Group 4: DS-Cav1 (150 mcg) + alum; Group 6:DS-Cav1 (500 mcg) + alum

VRC-RSVRGP084-00-VP BIOLOGICAL

VRC-RSVRGP084-00-VP is an investigational respiratory syncytial virus (RSV) vaccine.

Also known as: DS-Cav1

Group 1: DS-Cav1 (50 mcg); Group 2: DS-Cav1 (50 mcg) + alum; Group 3: DS-Cav1 (150 mcg); Group 4: DS-Cav1 (150 mcg) + alum; Group 5: DS-Cav1 (500 mcg); Group 6:DS-Cav1 (500 mcg) + alum

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 50 years of age.
• Willing and able to complete the informed consent process.
• Available for clinic visits through 44 weeks after enrollment.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• Willing to donate blood and mucosal samples to be stored and used for future research.
• In good general health without clinically significant medical history.
• Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) less than or equal to 40 within the 56 days prior to enrollment. Laboratory criteria within 56 days prior to enrollment:
• White Blood Cell (WBC) and differential either within institutional normal range or accompanied by Principal Investigator (PI) or designee approval.
• Platelets = 125,000-500,000/mm\^3.
• Hemoglobin within institutional normal range.
• Creatinine less than or equal to 1.1 x upper limit of normal (ULN).
• Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN.
• Negative for HIV infection by an FDA approved method of detection.
• Criteria applicable to women of childbearing potential:
• Negative result on a human chorionic gonadotropin pregnancy test on day of enrollment before receiving study product.

You may not qualify if:

• Criteria applicable to women of childbearing potential:
• Breast-feeding or planning to become pregnant through 4 weeks after the last injection.
• Subject has received any of the following:
• More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment.
• Blood products within 16 weeks prior to enrollment.
• Live attenuated vaccines within 4 weeks prior to enrollment.
• Inactivated vaccines within 2 weeks prior to enrollment.
• Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study.
• Current allergen immunotherapy with antigen injections, unless on maintenance schedule.
• Current anti-tuberculosis(TB) prophylaxis or therapy.
• Subject has any of the following:
• Serious reactions to vaccines that preclude receipt of study injections as determined by the investigator.
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• Asthma that is not well controlled.
• Diabetes mellitus (type I or II), with the exception of gestational diabetes.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Ruckwardt TJ, Morabito KM, Graham BS. Determinants of early life immune responses to RSV infection. Curr Opin Virol. 2016 Feb;16:151-157. doi: 10.1016/j.coviro.2016.01.003. Epub 2016 Mar 15.

  PMID: 26986236 BACKGROUND

• Ngwuta JO, Chen M, Modjarrad K, Joyce MG, Kanekiyo M, Kumar A, Yassine HM, Moin SM, Killikelly AM, Chuang GY, Druz A, Georgiev IS, Rundlet EJ, Sastry M, Stewart-Jones GB, Yang Y, Zhang B, Nason MC, Capella C, Peeples ME, Ledgerwood JE, McLellan JS, Kwong PD, Graham BS. Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera. Sci Transl Med. 2015 Oct 14;7(309):309ra162. doi: 10.1126/scitranslmed.aac4241.

  PMID: 26468324 BACKGROUND

• Graham BS, Modjarrad K, McLellan JS. Novel antigens for RSV vaccines. Curr Opin Immunol. 2015 Aug;35:30-8. doi: 10.1016/j.coi.2015.04.005. Epub 2015 Jun 10.

  PMID: 26070108 BACKGROUND

• Crank MC, Ruckwardt TJ, Chen M, Morabito KM, Phung E, Costner PJ, Holman LA, Hickman SP, Berkowitz NM, Gordon IJ, Yamshchikov GV, Gaudinski MR, Kumar A, Chang LA, Moin SM, Hill JP, DiPiazza AT, Schwartz RM, Kueltzo L, Cooper JW, Chen P, Stein JA, Carlton K, Gall JG, Nason MC, Kwong PD, Chen GL, Mascola JR, McLellan JS, Ledgerwood JE, Graham BS; VRC 317 Study Team. A proof of concept for structure-based vaccine design targeting RSV in humans. Science. 2019 Aug 2;365(6452):505-509. doi: 10.1126/science.aav9033.

  PMID: 31371616 BACKGROUND

• Chang LA, Phung E, Crank MC, Morabito KM, Villafana T, Dubovsky F, Falloon J, Esser MT, Lin BC, Chen GL, Graham BS, Ruckwardt TJ. A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine. Sci Transl Med. 2022 Dec 21;14(676):eade0424. doi: 10.1126/scitranslmed.ade0424. Epub 2022 Dec 21.

  PMID: 36542692 DERIVED

• Ruckwardt TJ, Morabito KM, Phung E, Crank MC, Costner PJ, Holman LA, Chang LA, Hickman SP, Berkowitz NM, Gordon IJ, Yamshchikov GV, Gaudinski MR, Lin B, Bailer R, Chen M, Ortega-Villa AM, Nguyen T, Kumar A, Schwartz RM, Kueltzo LA, Stein JA, Carlton K, Gall JG, Nason MC, Mascola JR, Chen G, Graham BS; VRC 317 study team. Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial. Lancet Respir Med. 2021 Oct;9(10):1111-1120. doi: 10.1016/S2213-2600(21)00098-9. Epub 2021 Apr 14.

  PMID: 33864736 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

aluminum sulfate

Results Point of Contact

• Title: Martin Gaudinski, MD
• Organization: Vaccine Research Center, NIAID, NIH

martin.gaudinski@nih.gov

(301) 451-8715

Study Officials

• Grace L Chen, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2017
• First Posted: February 10, 2017
• Study Start: February 22, 2017
• Primary Completion: October 3, 2019
• Study Completion: October 3, 2019
• Last Updated: October 23, 2020
• Results First Posted: October 23, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)