Safety and Immunogenicity Study to Evaluate Single- or Two-Dose Regimens Of RSV F Vaccine With and Without Aluminum Phosphate or Matrix-M1™ Adjuvants In Clinically-Stable Older Adults

• ClinicalTrials.gov Identifier: NCT03026348
• Recruitment Status: Completed
• First Posted: January 20, 2017
• Last Update Posted: August 31, 2018
• Sponsor: Novavax
• Information provided by (Responsible Party): Novavax

Study Description

Brief Summary:

This is a randomized, observer-blind, trial in clinically-stable older adults. Up to 300 eligible older adults 60 through 80 years of age will be enrolled at a 1:1 ratio into multiple dose/formulation treatment arms. Safety and immunogenicity data through Day 56 will be used to select a vaccine candidate to potentially evaluate in a Part 2 study. Proportions of subjects in various strata will not be pre-specified and the goal will be to achieve an approximately equal distribution of subjects with these characteristics across the treatment groups. Serology measures consistent with the study outcomes will be reported.

Condition or disease	Intervention/treatment	Phase
Respiratory Syncytial Viruses	Biological: RSV F Vaccine with Aluminum Phosphate Adjuvant; Biological: RSV F Vaccine; Biological: Matrix-M1 Adjuvant; Other: Phosphate Buffer	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity Study to Evaluate Single- or Two-Dose Regimens Of RSV F Vaccine With and Without Aluminum Phosphate or Matrix-M1™ Adjuvants In Clinically-Stable Older Adults
• Study Start Date: January 2017
• Actual Primary Completion Date: April 2017
• Actual Study Completion Date: May 18, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment Group A; Day 0 RSV F Vaccine 135µg/0.5mL Day 21 Phosphate Buffer	Biological: RSV F Vaccine; Other: Phosphate Buffer
Active Comparator: Treatment Group B; Day 0 Treatment / Formulation 1 Day 21 Phosphate Buffer	Biological: RSV F Vaccine with Aluminum Phosphate Adjuvant; Other: Phosphate Buffer
Active Comparator: Treatment Group C; Day 0 Treatment / Formulation 1 Day 21 Treatment / Formulation 1	Biological: RSV F Vaccine with Aluminum Phosphate Adjuvant
Active Comparator: Treatment Group D; Day 0 Treatment / Formulation 2 Day 21 Phosphate Buffer	Biological: RSV F Vaccine with Aluminum Phosphate Adjuvant; Other: Phosphate Buffer
Active Comparator: Treatment Group E; Day 0 Treatment / Formulation 2 Day 21 Treatment / Formulation 2	Biological: RSV F Vaccine with Aluminum Phosphate Adjuvant
Active Comparator: Treatment Group F; Day 0 Treatment / Formulation 3 Day 21 Phosphate Buffer	Biological: RSV F Vaccine; Biological: Matrix-M1 Adjuvant; Other: Phosphate Buffer
Active Comparator: Treatment Group G; Day 0 Treatment / Formulation 3 Day 21 Treatment / Formulation 3	Biological: RSV F Vaccine; Biological: Matrix-M1 Adjuvant
Active Comparator: Treatment Group H; Day 0 Treatment / Formulation 4 Day 21 Phosphate Buffer	Biological: RSV F Vaccine; Biological: Matrix-M1 Adjuvant; Other: Phosphate Buffer
Active Comparator: Treatment Group J; Day 0 Treatment / Formulation 4 Day 21 Treatment / Formulation 4	Biological: RSV F Vaccine; Biological: Matrix-M1 Adjuvant
Active Comparator: Treatment Group K; Day 0 Treatment / Formulation 5 Day 21 Phosphate Buffer	Biological: RSV F Vaccine; Biological: Matrix-M1 Adjuvant; Other: Phosphate Buffer
Active Comparator: Treatment Group L; Day 0 Treatment / Formulation 5 Day 21 Treatment / Formulation 5	Biological: RSV F Vaccine; Biological: Matrix-M1 Adjuvant
Placebo Comparator: Treatment Group M; Day 0 Phosphate Buffer Day 21 Phosphate Buffer	Other: Phosphate Buffer

Outcome Measures

Primary Outcome Measures :

1. Neutralizing antibody titers to at least one RSV/A strain [ Time Frame: Day 0, 21, 28 ]
2. Subjects with solicited local and systemic AEs occurring within the 7-day period following dosings on Day 0 and Day 21 and all adverse events, solicited and unsolicited, occurring within the 56-day period of Day 0. [ Time Frame: Day 0 - Day 6, Day 21 - Day 27; Day 0 - Day 56 ]

Secondary Outcome Measures :

1. Serum concentrations of antibodies competitive with palivizumab (i.e., PCA) for binding to the RSV F protein. [ Time Frame: Day 0, 21, 28, 56, 119, 385 ]
2. Serum IgG antibody concentrations as ELISA units (EUs) specific for the F protein antigen. [ Time Frame: Day 0, 21, 28, 56, 119, 385 ]
3. Counts of IFN-γ spot forming units following in vitro stimulation of Day 0, Day 7, and Day 28 PBMC isolates with RSV F peptides. [ Time Frame: Day 0, 7, 28 ]
4. Counts and proportions of Day 0, Day 7, and Day 28 peripheral blood T cells positive by intracellular staining for IL-2, IFN-γ, or TNF-α production (alone or any combination thereof) following in vitro stimulation with RSV F peptides. [ Time Frame: Day 0, 7, 28 ]

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Males and females 60 through 80 years of age who are ambulatory and live in the community or in an assisted-living facility that provides minimal assistance, such that the subject is primarily responsible for self-care and activities of daily living. Subjects may have one or more chronic medical diagnoses, but should be clinically stable as assessed by:

   • Absence of changes in medical therapy within one month due to treatment failure or toxicity (dose adjustments of ongoing therapies for optimal effect, or replacements within a class of drugs due to convenience or cost, will be deemed acceptable),
   • Absence of medical events qualifying as SAEs within one month of the planned vaccination on Day 0, and
   • Absence of known, current, and life-limiting diagnoses which, in the opinion of the investigator, render survival to completion of the protocol unlikely.
2. Willing and able (on both a physical and cognitive basis) to give informed consent prior to study enrollment. To complete the consent process, all qualifying subjects will correctly answer at least 4 out of 5 questions of the informed consent form (ICF) comprehension assessment in no more than 2 attempts.
3. Able to comply with study requirements. As the protocol procedures involve telephone contacts for safety ascertainment, eligible subjects must have a reliable access to a telephone.

Exclusion Criteria:

1. Received any prior RSV vaccine.
2. Participation in research involving any additional investigational product (drug / biologic / device) within 45 days before planned date of first vaccination.
3. History of a serious reaction to any prior vaccination or a history of Guillain-Barré syndrome (GBS) within 6 weeks of any prior influenza immunization.
4. Receipt of inactivated influenza vaccine within 14 days prior to the Day 0 dose of test article or any other vaccine within the 4 weeks prior to the Day 0 dose of test article.
5. Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination.
6. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
7. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study.
8. Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature ≥ 38.0°C on the planned day of vaccine administration).
9. Known disturbance of coagulation. Potential subjects receiving aspirin, clopidogrel, prasugrel, dipyridamole, dabigatran, apixaban, rivaroxaban, or warfarin under good control for cardiovascular prophylaxis or prophylaxis of thromboembolic disease or stroke in the setting of atrial fibrillation will NOT be excluded.
10. Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse.
11. Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled or could interfere with evaluation of the vaccine or interpretation of study results (including neurologic, cognitive, or psychiatric conditions deemed likely to impair the quality of study compliance or safety reporting).

Contacts and Locations

Locations

Australia, New South Wales

Research Site AU004

Sydney, New South Wales, Australia

Australia, Queensland

Research Site AU005

Herston, Queensland, Australia, 4006

Australia, South Australia

Research Site AU002

Adelaide, South Australia, Australia, 50000

Australia, Victoria

Research Site AU006

Prahran, Victoria, Australia, 3181

Australia, Western Australia

Resarch Site AU001

Nedlands, Western Australia, Australia, 6009

Sponsors and Collaborators

Novavax

Investigators

• Study Director: Vivek Shinde, MD; Novavax

More Information

• Responsible Party: Novavax
• ClinicalTrials.gov Identifier: NCT03026348
• Other Study ID Numbers: RSV-E-205
• First Posted: January 20, 2017
• Last Update Posted: August 31, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Novavax:

RSV

Additional relevant MeSH terms:

Aluminum phosphate; Vaccines; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic; Antacids; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents