A Study to Evaluate the Safety and Immunogenicity of MEDI7510 in Older Adults

NCT02289820 | Completed Phase 1 Results DMC

• 1 other identifier: D4420C00004
• Study Type: interventional
• Target: 363
• Locations: 1 country
• Sites: 5

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.

Conditions

Respiratory Syncytial Virus (RSV)

Keywords

RSV; Older adults; MEDI7510; Vaccine

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Solicited Symptoms

  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.

  Day 1 to Day 7

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

  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.

  From Day 1 to Day 29

• Percentage of Participants With Treatment-emergent Serious Adverse Events

  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.

  From Day 1 to Day 361

• Percentage of Participants With New Onset Chronic Diseases (NOCDs)

  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).

  From Day 1 to Day 361

• Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI)

  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).

  From Day 1 to Day 361

Secondary Outcomes (10)

• 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 Fold Rises (GMFRs) of Serum Antibodies Against RSV by RSV A Microneutralization Assay

  Day 29, 61, 91, 181, 271, and 361

• Percentage of Participants With Post-dose Seroresponse to RSV by RSV A Microneutralization Assay

  Day 29

• 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

• GMFRs of Serum Antibodies Against RSV by Anti F IgG Assay

  Day 29, 61, 91, 181, 271, and 361

Study Arms (5)

MEDI7510 (120 mcg sF + 1 mcg GLA), Cohort 1

EXPERIMENTAL

Participants will receive a single dose of MEDI7510 (120 microgram \[mcg\] respiratory syncytial virus \[RSV\] soluble fusion protein \[sF\] plus 1.0 mcg glucopyranosyl lipid A in 2% volume per volume stable emulsion) administered by intramuscular (IM) injection on Day 1.

Biological: MEDI7510

MEDI7510 (120 mcg sF + 2.5 mcg GLA), Cohort 2

EXPERIMENTAL

Participants will receive a single dose of MEDI7510 (120 mcg RSV sF plus 2.5 mcg glucopyranosyl lipid A in 2% volume per volume stable emulsion) plus IIV or MEDI7510 plus placebo administered by IM injection in contralateral arms on Day 1.

Biological: MEDI7510; Biological: IIV

MEDI7510 (120 mcg sF + 5 mcg GLA), Cohort 3

EXPERIMENTAL

Participants will receive a single dose of MEDI7510 (120 mcg RSV sF plus 5.0 mcg glucopyranosyl lipid A in 2% volume per volume stable emulsion) plus IIV or MEDI7510 plus placebo administered by IM injection in contralateral arms on Day 1.

Biological: MEDI7510

MEDI7510 (80 mcg sF + 2.5 mcg GLA), Cohort 4

EXPERIMENTAL

Participants will receive a single dose of MEDI7510 (80 mcg RSV sF plus 2.5 mcg glucopyranosyl lipid A in 2% volume per volume stable emulsion) administered by IM injection on Day 1.

Biological: MEDI7510

Inactivated Influenza Vaccine (IIV)

ACTIVE COMPARATOR

Participants will receive a single dose of IIV by intramuscular injection in contralateral arms on Day 1.

Biological: IIV

Interventions

MEDI7510 BIOLOGICAL

RSV sF antigen plus adjuvant

MEDI7510 (120 mcg sF + 1 mcg GLA), Cohort 1; MEDI7510 (120 mcg sF + 2.5 mcg GLA), Cohort 2; MEDI7510 (120 mcg sF + 5 mcg GLA), Cohort 3; MEDI7510 (80 mcg sF + 2.5 mcg GLA), Cohort 4

IIV BIOLOGICAL

Marketed Inactivated Influenza Vaccine

Inactivated Influenza Vaccine (IIV); MEDI7510 (120 mcg sF + 2.5 mcg GLA), Cohort 2

Eligibility Criteria

• Age: 60 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• History of splenectomy or of condition affecting splenic function (eg, hemoglobinopathy)
• History of cancer within preceding 5 years other than treated non-melanoma skin cancer
• Body Mass Index 40 or higher
• Receipt of any nonstudy vaccine within 30 days prior to study dosing or expected receipt of nonstudy vaccine within 30 days after study dosing
• Receipt of any investigational product in the 90 days prior to randomization or expected receipt of investigational product during the period of study follow-up

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (5)

Research Site

Orlando, Florida, United States

Location

Research Site

South Miami, Florida, United States

Location

Research Site

Kansas City, Missouri, United States

Location

Research Site

Raleigh, North Carolina, United States

Location

Research Site

Nashville, Tennessee, United States

Location

Related Publications (2)

• 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

• Falloon J, Talbot HK, Curtis C, Ervin J, Krieger D, Dubovsky F, Takas T, Yu J, Yu L, Lambert SL, Villafana T, Esser MT. Dose Selection for an Adjuvanted Respiratory Syncytial Virus F Protein Vaccine for Older Adults Based on Humoral and Cellular Immune Responses. Clin Vaccine Immunol. 2017 Sep 5;24(9):e00157-17. doi: 10.1128/CVI.00157-17. Print 2017 Sep.

  PMID: 28679495 DERIVED

Results Point of Contact

• Title: Judith Falloon, MD, FACP, FIDSA, Senior Director, Clinical Development
• Organization: MedImmune LLC

information.center@astrazeneca.com

+1-301-398-4010

Study Officials

• Judith Falloon, MD

  MedImmune LLC

  STUDY DIRECTOR

• Eric Sheldon, MD

  Miami Research Associates

  PRINCIPAL INVESTIGATOR

• Craig Curtis, MD

  Compass Research

  PRINCIPAL INVESTIGATOR

• John Ervin, MD

  The Center for Pharmaceutical Research

  PRINCIPAL INVESTIGATOR

• Wayne Harper, MD

  Wake Research Associates

  PRINCIPAL INVESTIGATOR

• H. Keipp Talbot, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: November 13, 2014
• Study Start: January 5, 2015
• Primary Completion: February 24, 2016
• Study Completion: February 24, 2016
• Last Updated: March 15, 2018
• Results First Posted: February 19, 2018

Record last verified: 2018-02

Locations

US (5)