A Phase 1b Study to Evaluate the Safety and Immunogenicity of MEDI7510 in Older Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Respiratory Syncytial Virus (RSV)
- Sponsor
- MedImmune LLC
- Enrollment
- 363
- Locations
- 1
- Primary Endpoint
- Percentage of Participants With Solicited Symptoms
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The goal of this study is to evaluate the safety, tolerability and immunogenicity of ascending doses of adjuvant in combination with a single dosage level of RSV sF in adults 60 years or older who are healthy or who have stable, chronic underlying medical conditions. This study will also provide preliminary safety and immunogenicity data to support concurrent dosing of MEDI7510 with influenza vaccine (IIV), and to assess the safety of MEDI7510 at a dose previously assessed in the Phase 1a study.
Detailed Description
A Phase 1b, double-blind, randomized, controlled cohort escalation study evaluating the safety, tolerability and immunogenicity of MEDI7510. Approximately 264 subjects will be enrolled at approximately 5 study centers in the US and randomized by cohort (Cohort 1 \[4:1\]; Cohorts 2 and 3 \[8:8:3\]; Cohort 4 \[5:1\]) to receive a single intramuscular dose of 1 study vaccine (Cohorts 1 and 4) or a single intramuscular dose of each of 2 study vaccines (Cohorts 2 and 3) administered in contralateral arms. Cohort 1: MEDI7510 formulation (n = 40) or IIV (n = 10) Cohort 2: MEDI7510 formulation and placebo (n = 40) or MEDI7510 formulation and IIV (n = 40) or placebo and IIV (n = 15) Cohort 3: MEDI7510 formulation and placebo (n = 40) or MEDI7510 formulation and IIV (n = 40) or placebo and IIV (n = 15) Cohort 4: MEDI7510 formulation (n = 20) or IIV (n = 4)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age greater than or equal to 60 years
- •Ambulatory or ambulatory with assistance (not institutionalized, bedridden, or homebound)
- •Weight greater than 90 lbs
- •Hemoglobin greater than or equal to 10.5 g/dL for women and greater than or equal to 11 g/dL for men
- •Subject able to complete follow-up period of 360 days after dosing
Exclusion Criteria
- •History of allergy to: any component of the vaccine; IIV or intolerance of IIV; eggs in adulthood
- •Receipt of seasonal flu shot within 60 days prior to dosing
- •Any unstable acute or chronic medical condition, including one that has resulted in change in therapy (medication or other) in the 30 days prior to randomization or hospitalization in the previous year or might be predicted to result in hospitalization in the year after enrollment. Subjects with severe, untreated or uncontrolled underlying medical disease that might either compromise subject safety or affect the ability to assess safety of the investigational product are excluded. Medications taken on an as-needed basis are permitted to start or stop during the 30 days prior to randomization unless they are medications not previously taken by the subject
- •Clinically significant abnormalities in screening laboratory assessments or screening ECG
- •History of hepatitis B or hepatitis C infection
- •History of Guillain-Barré syndrome
- •Cognitive disorder such that informed consent cannot be obtained directly from the subject
- •Previous vaccination against RSV
- •History of or current autoimmune disorder
- •Immunosuppression caused by disease, including human immunodeficiency virus (HIV) infection, or medications. Any oral prednisone dosing within 30 days of enrollment or planned dosing within the 360-day follow-up period would disqualify. Expected need for immunosuppressive medications during the 360-day follow-up period would disqualify
Outcomes
Primary Outcomes
Percentage of Participants With Solicited Symptoms
Time Frame: Day 1 to Day 7
Solicited symptoms are events that are considered likely to occur post dosing and included the local reaction (pain, tenderness or soreness, redness, and swelling at the site of injection) to investigational product (IP) injection and systemic symptoms (fever greater than or equal to \[\>=\] 100.4°F \[\>=38°C\] by any route, headache, generalized muscle aches, and fatigue or tiredness) that might be related to IP injection. Solicited symptoms were not coded using Medical Dictionary for Regulatory Activities (MedDRA) and summarized regardless of whether or not they are treatment emergent. The percentage of participants with solicited symptoms were recorded during Days 1 (day of dosing) through 7.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: From Day 1 to Day 29
An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Treatment-emergent were the events between administration of study drug and including the follow-up period through Day 29. The AEs were summarized using the Medical Dictionary for Regulatory Activities version 18.1.
Percentage of Participants With Treatment-emergent Serious Adverse Events
Time Frame: From Day 1 to Day 361
A serious adverse event (SAE) was an AE resulting in any of following reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk), persistent or significant disability/incapacity, congenital anomaly, and a medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above.
Percentage of Participants With New Onset Chronic Diseases (NOCDs)
Time Frame: From Day 1 to Day 361
A NOCD was a newly diagnosed medical condition that is of a chronic, ongoing nature. It was observed after receiving study drug and was assessed by investigator as medically significant. All NOCDs were recorded from the time of dosing through the day of the last participant contact (Day 361 visit).
Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI)
Time Frame: From Day 1 to Day 361
An AESI was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. Treatment emergent AESIs were collected from the time of dosing through the day of the last participant contact (Day 361 visit).
Secondary Outcomes
- Geometric Mean Concentrations of Serum Antibodies Against RSV by Anti F Immunoglobulin G (IgG) Assay(Baseline (Day 1), Day 29, 61, 91, 181, 271, and 361)
- Geometric Mean Titers (GMTs) of Serum Antibodies Against Respiratory Syncytial Virus (RSV) by RSV A Microneutralization Assay(Baseline (Day 1), Day 29, 61, 91, 181, 271, and 361)
- Geometric Mean Counts of Cellular Immune Response Against RSV by Respiratory Syncytial Virus Fusion Protein (RSV F) Interferon Gamma (IFNγ) Enzyme-linked Immunosorbent Spot (ELISPOT) Assay(Baseline (Day 1) and Day 8)
- Geometric Mean Fold Rises (GMFRs) of Serum Antibodies Against RSV by RSV A Microneutralization Assay(Day 29, 61, 91, 181, 271, and 361)
- GMFRs of Cellular Immune Response Against RSV by RSV F IFNγ ELISPOT Assay(Day 8)
- Percentage of Participants With Post-dose Seroresponse to RSV by RSV A Microneutralization Assay(Day 29)
- GMFRs of Serum Antibodies Against RSV by Anti F IgG Assay(Day 29, 61, 91, 181, 271, and 361)
- Percentage of Participants With Post-dose Seroresponse to RSV by Anti-F IgG Assay(Day 29)
- Ratios of GMTs and GMFRs of Hemagglutination Inhibition (HAI) Antibodies(Day 29)
- Percentage of Participants With Post-dose Cell-mediated Immune Response to RSV F by RSV F Peptide Pool IFNγ ELISPOT(Day 8)