The Safety, Tolerance, and Immunogenicity of MAS-1-Adjuvanted Seasonal Inactivated Influenza Vaccine (MER4101)

NCT02500680 | Unknown Phase 1 DMC

• 1 other identifier: MPE002
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerance, and immunogenicity of MAS-1-Adjuvanted seasonal inactivated influenza vaccine (IIV) (MER4101) with hemagglutinin dose escalation compared to non-adjuvanted comparator IIV standard dose (SD) in healthy adults and high dose (HD) IIV in ambulatory elderly subjects. Hypothesis: Reduced HA dose IIV formulated in MAS-1 adjuvant (MER4101) has been shown under Phase 1A to be safe, tolerable and demonstrated a more robust and durable immune response to IIV over 6 months post-vaccination in healthy young adults 18 - 49 years of age compared to SD IIV. Under phase 1B, the 9 µg/HA dose of IIV in 0.3 mL MAS-1 was safe and well tolerated and immunogenically comparable to or better than 60 µg/HA HD IIV control over 3 to 6 months post-vaccination than HD IIV control. It is anticipated that the increased total dose of 15 µg HA antigen administered concurrently to opposite arms in 2 doses of 7.5 µg/HA IIV in 0.25 mL MAS-1 adjuvant emulsion will be safe, well tolerated, and more immunogenic than 9 µg/HA IIV in MAS-1, and will be more immunogenic when compared to HD IIV control in adults who are 65 years of age and older with the potential to provide better protection throughout the influenza season.

Conditions

Influenza, Human

Keywords

Influenza; Adjuvant

Outcome Measures

Primary Outcomes (7)

• Number of Participants with solicited local and systemic AEs

  14 Days after Vaccination

• Number of Participants with Late-Onset Local and Systemic AEs

  16 days after Vaccination for the remaining duration of the study

• Number of Participants with laboratory abnormalities

  7, 14 and 28 Days after Vaccination

• Occurrence of vaccine-related SAEs

  Duration of Study

• Geometric mean titer (GMT) of hemagglutination inhibition assay (HAI) antibodies

  28 days after Vaccination

• Seroconversion rate of HAI antibody titer

  28 days after Vaccination

• Geometric mean fold increase (GMFI) of HAI antibodies (post-vaccination titer relative to pre-vaccination titer)

  28, 84, and 168 days after Vaccination

Secondary Outcomes (4)

• Occurrence of unsolicited AEs related to vaccine

  1 to 14, 15 to 29, and 30 to 85 Days after Vaccination

• Occurrence of adverse events of special interest (AESI)

  Up to 12 months after Vaccination

• Comparison of rates of unsolicited AEs related to vaccine at intervals following vaccination

  1 to 14 days, 15 to 29 days, and 30 to 85 days after Vaccination

• Seroprotection rate of HAI antibody titers (proportion of participants with ≥40 reciprocal antibody titer)

  7, 14, 28, 84, and 168 days after Vaccination

Other Outcomes (3)

• Seroprotection rate of HAI antibody titers (proportion of participants with ≥1:80, 1:160, and 1:320 HAI antibody titer for each of the strains)

  7, 14, 28, 84, and 168 days after Vaccination

• GMFI of HAI antibodies

  7 and 14 days after Vaccination

• GMT of HAI antibodies to non-vaccine strains of influenza A and B

  28 and 84 days after Vaccination

Study Arms (11)

Group 1 (Phase 1A)

EXPERIMENTAL

MER4101 (MAS-1 Adjuvanted IIV \[Fluzone quadrivalent influenza vaccine, Sanofi Pasteur\]) 1µg (Standard Dose) Single Dose

Biological: MER4101

Group 2 (Phase 1A)

EXPERIMENTAL

MER4101 (MAS-1 Adjuvanted IIV \[Fluzone quadrivalent influenza vaccine, Sanofi Pasteur\]) 3µg (Standard Dose) Single Dose

Biological: MER4101

Group 3 (Phase 1A)

EXPERIMENTAL

MER4101 (MAS-1 Adjuvanted IIV \[Fluzone quadrivalent influenza vaccine, Sanofi Pasteur\]) 5µg (Standard Dose) Single Dose

Biological: MER4101

Group 4 (Phase 1A)

EXPERIMENTAL

MER4101 (MAS-1 Adjuvanted IIV \[Fluzone quadrivalent influenza vaccine, Sanofi Pasteur\]) 9µg (Standard Dose) Single Dose

Biological: MER4101

Group 5A (Phase 1A)

ACTIVE COMPARATOR

Fluzone quadrivalent influenza vaccine (Sanofi Pasteur) 15µg (Standard Dose) Single Dose

Biological: Inactivated Influenza Vaccine

Group 5B (Phase 1B)

ACTIVE COMPARATOR

Fluzone quadrivalent influenza vaccine (Sanofi Pasteur) 60µg (High Dose) Single Dose

Biological: Inactivated Influenza Vaccine

Group 6 (Phase 1B)

EXPERIMENTAL

MER4101 (MAS-1 Adjuvanted IIV \[Fluzone quadrivalent influenza vaccine, Sanofi Pasteur\]) Optimal Vaccine Dose from Phase 1A (9µg) (Standard Dose) Single Dose

Biological: MER4101

Group 7A (Phase 1B extension)

EXPERIMENTAL

MER4101 (MAS-1 Adjuvanted IIV \[Fluzone quadrivalent influenza vaccine, Sanofi Pasteur\]) 9µg/HA in 0.5 mL MAS-1 emulsion (Standard Dose) Single Dose

Biological: MER4101

Group 7B (Phase 1B extension)

ACTIVE COMPARATOR

Fluzone quadrivalent influenza vaccine (Sanofi Pasteur) 60µg (High Dose) Single Dose

Biological: Inactivated Influenza Vaccine

Group 8A (Phase 1B extension)

EXPERIMENTAL

MER4101 (MAS-1 Adjuvanted IIV \[Fluzone quadrivalent influenza vaccine, Sanofi Pasteur\]) 15µg/HA in 0.5 mL MAS-1 emulsion (Standard Dose) Single Dose (as 2 x 0.25 mL in each arm)

Biological: MER4101

Group 8B (Phase 1B extension)

ACTIVE COMPARATOR

Fluzone quadrivalent influenza vaccine (Sanofi Pasteur) 60µg (High Dose) Single Dose (0.5 mL) in one arm and 0.5 mL of PBS in the other arm

Biological: Inactivated Influenza Vaccine

Interventions

MER4101 BIOLOGICAL

Also known as: Inactivated Influenza Vaccine with MAS-1 Adjuvant

Group 1 (Phase 1A); Group 2 (Phase 1A); Group 3 (Phase 1A); Group 4 (Phase 1A); Group 6 (Phase 1B); Group 7A (Phase 1B extension); Group 8A (Phase 1B extension)

Inactivated Influenza Vaccine BIOLOGICAL

Fluzone quadrivalent Influenza Vaccine

Group 5A (Phase 1A); Group 5B (Phase 1B); Group 7B (Phase 1B extension); Group 8B (Phase 1B extension)

Eligibility Criteria

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

You may qualify if:

• Specifically Phase 1A:
• Males or non-pregnant females, 18 to 49 years old, inclusive.
• Female subjects of childbearing potential who must agree to practice avoidance of pregnancy, including use of acceptable forms of contraception.
• Pulse is 55 to 100 bpm, inclusive.
• Systolic blood pressure is 90 to 140 mmHg, inclusive.
• Diastolic blood pressure is 55 to 90 mmHg, inclusive.
• For Phase 1B and Phase 1B Extension:
• Ambulatory persons aged at least 65 years or older on the day of enrollment. Subjects will be considered ambulatory if they are not institutionalized, bedridden, or homebound.
• Pulse is 50 to 115 bpm, inclusive.
• Systolic blood pressure is 85 to 160 mmHg, inclusive.
• Diastolic blood pressure is 55 to 95 mmHg, inclusive.
• For Phase 1A, Phase 1B, and Phase 1B Extension:
• Written informed consent form and Authorization to Obtain and Release Protected Health Information (HIPAA) form signed, prior to initiation of any study procedures
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Are in good health, as determined by vital signs, medical history, and physical examination based on medical history to ensure any existing medical diagnoses or conditions are stable.

You may not qualify if:

• Specifically Phase 1A:
• Female subjects who are breastfeeding or plan to breastfeed at any given time from the study vaccination until 30 days after the study vaccination will be ineligible
• Receipt of 2014-2015 and 2015-2016 seasonal influenza vaccine.
• After 03 September 2015, any subject who intends to receive the 2015-2016 licensed influenza vaccine within 3 months after receiving study vaccination.
• After 03 September 2015, any subject who has household contact with infants less than 1 year of age, persons 65 years of age and older, or immunocompromised individuals.
• For Phase 1B and Phase 1B Extension:
• \. Receipt of seasonal influenza vaccine in the past six months and planned receipt of seasonal influenza vaccine within 3 months after receiving study vaccination.
• Specifically Phase 1B Extension:
• History of medically-attended altered mental status or inner ear (not including hearing loss), labyrinth and cerebellar disorders within 3 months prior to enrollment.
• Use of concomitant medications that may be nephrotoxic as judged by the investigator.
• For Phase 1A, Phase 1B and Phase 1B Extension:
• Inability to provide informed consent or complete study activities, for example, due to dementia or other impairment.
• Have an acute illness within 72 hours prior to study vaccination
• An acute febrile illness within 24 hours prior to vaccination. Vaccination will be deferred until the participant has been afebrile for at least 24 hours.
• Signs and symptoms of an acute infectious respiratory illness. Vaccination will be deferred until the symptoms resolve.

Sponsors & Collaborators

• Nova Immunotherapeutics Limited: lead
• Mercia Pharma Inc.: collaborator
• Nova Laboratories Limited: collaborator
• The Emmes Company, LLC: collaborator

Study Sites (1)

Saint Louis University School of Medicine

St Louis, Missouri, 63104, United States

Location

Related Publications (2)

• Gorse GJ, Grimes S, Buck H, Mulla H, White P, Hill H, May J, Frey SE, Blackburn P. MAS-1, a novel water-in-oil adjuvant/delivery system, with reduced seasonal influenza vaccine hemagglutinin dose may enhance potency, durability and cross-reactivity of antibody responses in the elderly. Vaccine. 2022 Mar 1;40(10):1472-1482. doi: 10.1016/j.vaccine.2022.01.035. Epub 2022 Feb 4.

  PMID: 35125224 DERIVED

• Gorse GJ, Grimes S, Buck H, Mulla H, White P, Hill H, May J, Frey SE, Blackburn P. A phase 1 dose-sparing, randomized clinical trial of seasonal trivalent inactivated influenza vaccine combined with MAS-1, a novel water-in-oil adjuvant/delivery system. Vaccine. 2022 Feb 23;40(9):1271-1281. doi: 10.1016/j.vaccine.2022.01.034. Epub 2022 Feb 4.

  PMID: 35125219 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Geoffrey J Gorse, MD

  St. Louis University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: July 16, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: September 6, 2019

Record last verified: 2019-09

Locations

US (1)