A Study to Evaluate the Efficacy of MEDI7510 in Older Adults

Respiratory Syncytial Virus Clinical Trial

Official title:

A Phase 2b Randomized, Double-blind Study to Evaluate the Efficacy of MEDI7510 for the Prevention of Acute Respiratory Syncytial Virus-associated Respiratory Illness in Older Adults

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02508194
• Other study ID #: D4420C00005
• Status: Terminated
• Phase: Phase 2
• First received: July 22, 2015
• Last updated: December 22, 2017
• Start date: September 29, 2015
• Est. completion date: November 7, 2016

Study information

• Verified date: December 2017
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will be the first assessment of the efficacy of MEDI7510 for the prevention of respiratory syncytial virus (RSV) disease. It will also provide estimates of vaccine efficacy and of endpoint incidence in the placebo arm. It will also assess the safety and immunogenicity of concurrent dosing of MEDI7510 and IIV to expand on the observations made in the Phase 1b study of MEDI7510. It will also expand the safety database of participants dosed with MEDI7510. The study will also assess the immune response to MEDI7510 in Season 1 and Season 2.

Description:

A Phase 2b, double-blind, randomized, and controlled study to evaluate the efficacy of MEDI7510 in approximately 1,900 adult participants, globally, 60 years or older. Participants will be randomized in a 1:1 ratio to receive a single intramuscular dose of each of 2 study vaccines in contralateral arms: MEDI7510 + IIV or placebo + IIV in Season 1.

Participants who receive MEDI7510 in the Northern Hemisphere will be re-randomized and blinded in Season 2 to receive either MEDI7510 + IIV or placebo + IIV in a 1:1 ratio. Clinical efficacy will not be assessed in Season 2; however the safety of revaccination will be assessed in Season 2.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1900
• Est. completion date: November 7, 2016
• Est. primary completion date: September 9, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 99 Years

Eligibility

Inclusion Criteria:

• Age = 60 years at the time of screening.

• Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the subject appears likely to be able to remain in follow-up through the end of protocol-specified follow-up.

• (Season 2): Subject received MEDI7510 and IIV in the Northern Hemisphere in Season 1.

Exclusion Criteria:

• History of allergy to any component of the vaccine.

• Receipt of seasonal influenza vaccine within 6 months prior to Season 1 dosing.

• History of allergy to or intolerance of IIV.

• Pregnancy or potential to become pregnant during the study. Females who (1) have had a menstrual period within the 12 months prior to study enrollment or (2) are undergoing any fertility treatment or who plan to undergo fertility treatments during the study period are excluded.

• History of Guillain-Barré syndrome.

• Previous vaccination against RSV.

• History of allergy to eggs in adulthood.

• History of or current autoimmune disorder, with the exception of stable, treated hypothyroidism caused by autoimmune thyroiditis, which is acceptable.

• Immunosuppression caused by disease, including human immunodeficiency virus infection (assessed by history), or medications. Any receipt of oral or intravenous glucocorticoid therapy within 30 days prior to enrollment or planned dosing within the follow-up period would disqualify. Topical, intranasal, inhaled, or intra-articular corticosteroids do not disqualify. Expected need for immunosuppressive medications during the follow-up period would disqualify.

• History of cancer within preceding 5 years other than treated non-melanoma skin cancer, locally-treated cervical cancer or in situ carcinoma of the breast.

• Receipt of any non-study vaccine within 28 days prior to study dosing or expected receipt of non-study vaccine prior to the Day 29 visit in Season 1.

• Receipt of any investigational product (IP) in the 90 days prior to randomization or expected receipt of IP during the period of study follow-up.

• Receipt of immunoglobulins or blood products within 4 months of study dosing (120 days) or expected receipt of immunoglobulins or blood products during the period of study follow-up.

• Current bleeding or clotting disorder including use of anticoagulants other than drugs with anti-platelet activity (such as nonsteroidal anti-inflammatory drugs, clopidogrel, ticagrelor or aspirin).

• History of alcohol or drug abuse or psychiatric disorder that, in the opinion of the investigator, would affect the subject's safety or compliance with study.

• (Season 2): Related Grade 3 or 4 adverse event (AE) including Grade 3 or 4 local reaction to either MEDI7510 or IIV, any adverse event of special interest (AESI) for an adjuvanted vaccine, or any related serious adverse event (SAE).

Related Conditions & MeSH terms

• Respiratory Syncytial Virus

Intervention

Biological:
• MEDI7510
RSV soluble fusion protein (sF) antigen plus glucopyranosyl lipid A in stable emulsion (GLA-SE) adjuvant
• IIV
Marketed Inactivated Influenza Vaccine

Other:
• Placebo
Sterile Saline

Locations

Country	Name	City	State
Canada	Research Site	Brampton	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
Estonia	Research Site	Paide
Estonia	Research Site	Tallinn
Estonia	Research Site	Tallinn
Estonia	Research Site	Tallinn
Latvia	Research Site	Daugavpils
Latvia	Research Site	Jelgava
Latvia	Research Site	Kuldiga
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Vilnius
Lithuania	Research Site	Vilnius
South Africa	Research Site	Bellville
South Africa	Research Site	Bloemfontein
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Krugersdorp
South Africa	Research Site	Pretoria
South Africa	Research Site	Somerset West
United States	Research Site	Akron	Ohio
United States	Research Site	Augusta	Kansas
United States	Research Site	Aurora	Colorado
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Champaign	Illinois
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Missouri
United States	Research Site	Council Bluffs	Iowa
United States	Research Site	Dakota Dunes	South Dakota
United States	Research Site	Edina	Minnesota
United States	Research Site	Hickory	North Carolina
United States	Research Site	Kansas City	Missouri
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Lady Lake	Florida
United States	Research Site	Littleton	Colorado
United States	Research Site	Miami	Florida
United States	Research Site	Murray	Utah
United States	Research Site	Nashville	Tennessee
United States	Research Site	Norfolk	Nebraska
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orlando	Florida
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Rochester	New York
United States	Research Site	Rocky Mount	North Carolina
United States	Research Site	Sacramento	California
United States	Research Site	San Francisco	California
United States	Research Site	Savannah	Georgia
United States	Research Site	Wichita	Kansas
United States	Research Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Estonia,  Latvia,  Lithuania,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Had a First Episode of Acute Respiratory Syncytial Virus-Associated Respiratory Illness (ARA-RI) During Respiratory Syncytial Virus (RSV) Surveillance Period in Season 1	ARA-RI was defined as an event in which a participant met specified clinical criteria and the event was laboratory-confirmed to be RSV-related. The specified clinical criteria included a minimum of 1 symptom from any 2 of the 3 symptom columns: one symptom from upper respiratory symptom column and one symptom from lower respiratory symptom column; one symptom from upper respiratory symptom column and one symptom from systemic symptom column; or one symptom from lower respiratory column and one from systemic symptom column and laboratory confirmation of RSV on at least 1 sample obtained between Day 1 to Day 8 of illness. The surveillance period was approximately 7 months and Season 1 was approximately 1 year.	Day 14 after dosing through end of surveillance period (approximately 7 months)
Secondary	Percentage of Participants Who Had a RSV Polymerase Chain Reaction (PCR)-Positive Respiratory Illness During the RSV Surveillance Period in Season 1	Detection of RSV was done by PCR method by using any respiratory sample. The incidence of RSV PCR-positive respiratory illness during the RSV surveillance period was evaluated. The surveillance period was approximately 7 months and Season 1 was approximately 1 year.	Day 14 after dosing through end of surveillance period (approximately 7 months)
Secondary	Geometric Mean Responses (GMRs) of Serum Antibodies Concentration Against RSV by Anti-Fusion Protein (F) Immunoglobulin G (IgG) Assay	Anti-F IgG antibodies concentration were determined by a multiplex IgG assay developed on the Meso Scale discovery platform. It was calculated as: anti-log2 [mean (log2 xi)], where "xi" is an antibodies concentration of participants. The Season 1 was approximately 1 year.	Day 1, Day 29, and End of Season 1 (approximately 1 year)
Secondary	Geometric Mean Fold Change of Serum Antibodies Concentration Against RSV by Anti-F IgG Assay	Anti-F IgG antibodies concentration was determined by a multiplex IgG assay developed on the Meso Scale discovery platform. It was calculated as: anti-log2 [mean (log2 yi)], where "yi" is the post dose antibody concentration or T-cell count fold change from baseline for each participant. The Season 1 was approximately 1 year.	Day 29 and End of Season 1 (approximately 1 year)
Secondary	Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by Anti-F IgG Assay	Anti-F IgG antibodies were determined by a multiplex IgG assay developed on the Meso Scale discovery platform. Seroresponse was defined as a greater than or equal to (>=) 3-fold rise of serum antibodies against RSV from baseline. The Season 1 was approximately 1 year.	Day 29 and End of Season 1 (approximately 1 year)
Secondary	Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine	GMT was calculated as: anti-log2 [mean (log2 xi)], where "xi" is an antibodies concentration of participants. GMTs of strain-Specific HAI antibodies (H1N1, H3N2, B Brisbane, and B Phuket) were reported. The Season 1 was approximately 1 year.	Day 1 (post-dose) and Day 29 of Season 1
Secondary	Post-dose Geometric Mean Fold Change of Strain-Specific HAI Antibodies to Influenza Antigens Contained in the Seasonal Influenza Vaccine	Geometric mean fold change was calculated as: anti-log2 [mean (log2 yi)], where "yi" is the post dose antibody concentration or T-cell count fold change from baseline for each participant. Geometric mean fold change of strain-specific HAI antibodies (H1N1, H3N2, B BRISBANE, and B PHUKET) were reported. The Season 1 was approximately 1 year.	Day 29 of Season 1
Secondary	Percentage of Participants Who Had a Strain-specific Post-dose Seroresponse to HAI Antibody	Seroresponse was defined as a >= 4-fold rise of strain-specific HAI antibodies (H1N1, H3N2, B BRISBANE, and B PHUKET) from baseline. The Season 1 was approximately 1 year.	Day 29 of Season 1
Secondary	Post-dose GMTs of Serum Antibodies Against RSV by Microneutralization Assay	Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. GMT was to be calculated as: anti-log2 [mean (log2 xi)], where "xi" is an antibodies concentration of participants. The Season 1 was approximately 1 year.	Day 29 and End of Season 1 (approximately 1 year)
Secondary	Post-dose Geometric Mean Fold Change of Serum Antibodies Against RSV by Microneutralization Assay	Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Geometric mean fold change was to be calculated as: anti-log2 [mean (log2 yi)], where "yi" is the post dose antibody concentration or T-cell count fold rise from baseline for each participant. The Season 1 was approximately 1 year.	Day 29 and End of Season 1 (approximately 1 year)
Secondary	Percentage of Participants Who Had a Post-dose Seroresponse to RSV by Microneutralization Assay	Microneutralization assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Seroresponse was defined as a >= 3-fold rise of Serum Antibodies against RSV from baseline. The Season 1 was approximately 1 year.	Day 29 and End of Season 1 (approximately 1 year)
Secondary	Post-dose Geometric Mean Concentration (GMC) of Palivizumab Competitive Antibodies as Measured by a Palivizumab Competitive Enzyme Linked Immunosorbent Assay (cELISA)	Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. GMC was to be calculated as: anti-log2 [mean (log2 xi)], where "xi" is an antibodies concentration of participants. The Season 1 was approximately 1 year.	Day 29 and End of Season 1 (approximately 1 year)
Secondary	Post-dose Geometric Mean Fold Change of Palivizumab Competitive Antibodies as Measured by a Palivizumab cELISA	Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Geometric mean fold change was to be calculated as: anti-log2 [mean (log2 yi)], where "yi" is the post dose antibody concentration or T-cell count fold rise from baseline for each participant. The Season 1 was approximately 1 year.	Day 29 and End of Season 1 (approximately 1 year)
Secondary	Percentage of Participants Who Had a Post-dose Seroresponse to RSV as Measured by a Palivizumab cELISA	Palivizumab cELISA assay was to be used to assess humoral immunity (HAI antibody titers) against RSV. Seroresponse was defined as a >= 3-fold rise of Serum Antibodies against RSV from baseline. The Season 1 was approximately 1 year.	Day 29 and End of Season 1 (approximately 1 year)
Secondary	Number of Participants With Any Solicited Symptoms	Solicited symptoms: tenderness or soreness at site of injection, pain at site of injection, fatigue or tiredness, headache, generalized muscle aches, swelling at the site of injection, redness at the site of injection, fever >= 100.4 degrees Fahrenheit by any route from Day 1 to Day 7.	Day 1 (post-dose) through Day 7
Secondary	Number of Participants With Treatment-Emergent Adverse Events	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent events were between administration of study drug and Day 29 that were absent before treatment or that worsened relative to pre-treatment state.	Day 1 (post-dose) through Day 29
Secondary	Number of Participants With Treatment-Emergent Adverse Events of Special Interest (TEAESIs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent New Onset Chronic Disease (NOCDs)	An serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and approximately 1 year follow up that were absent before treatment or that worsened relative to pretreatment state. An adverse event of special interest was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. 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. The Season 1 was approximately 1 year.	Day 1 (post-dose) through end of Season 1 (approximately 1 year)