Immunogenicity and Safety of Group A, C, Y & W-135 Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine

A Phase 2 Double Blind Study to Evaluate Safety and Immunogenicity of Meningococcal Meningitis Serogroups A, C, Y & W-135 Polysaccharide Diphtheria Toxoid Conjugate Vaccine (NmVac4-A/C/Y/W-135-DT™) Compared With a Licensed Vaccine

The purpose of this study is to evaluate the production of antibodies to a new conjugate vaccine, NmVac4-A/C/Y/W-135-DT, as a measure of vaccine effectiveness, compared to the production of antibodies to a similar, licensed meningococcal (Groups A, C, Y, W-135) polysaccharide diphtheria toxoid (DT) conjugate vaccine. The investigators will also evaluate the safety of NmVac4-A/C/Y/W-135-DT™ conjugate vaccine compared to the licensed vaccine. The hypothesis is that the test vaccine is comparable to the licensed active control vaccine.

Study Overview

• Status: Completed
• Conditions: Meningococcal Infections; Meningococcal Meningitis
• Intervention / Treatment: Biological: Test Vaccine; Biological: US Licensed Vaccine

Detailed Description

Meningococcal disease is a potentially life-threatening bacterial infection. The disease most commonly is expressed as either meningococcal meningitis, an inflammation of the membranes surrounding the brain and spinal cord, or meningococcemia, the presence of bacteria in the blood. The most common symptoms include high fever, headache, neck stiffness, confusion, nausea, vomiting, lethargy, and rash. If not treated the disease can progress rapidly and can lead to shock and death, often within hours of the onset of symptoms. The disease is fatal at a rate of 10%. Of patients who recover, 10% have permanent hearing loss or other serious sequelae.

Neisseria meningitidis capsular polysaccharides are poor immunogens. However, conjugation of bacterial polysaccharides to immunogenic carrier proteins generally results in conjugates that induce strong anti-polysaccharide T-helper cell dependent immune responses, creating a longer-lasting immune response and thus protection against meningococcal infection.

The sponsor's small size Phase 1 clinical trial comprised 60 subjects. Therefore, additional data is needed to confirm the previous data with a statistically powered Phase 2 clinical trial. The present study aims to evaluate subject responses to single doses, administered in adult subjects, to determine further safety and immunogenicity of the vaccine. This study compares safety and antibody production induced by one intramuscular injection of either NmVac4-A/C/Y/W-135-DT or a licensed meningococcal (Groups A, C, Y, W-135) polysaccharide diphtheria toxoid conjugate vaccine. The primary immunogenicity endpoint will be seroresponse, based on antibody titer ≥1:8 for subjects with titer <1:8 at baseline or a 4-fold rise in antibody levels, 4 weeks after a single injection . The number and proportion of subjects achieving seroresponse will be tabulated by serogroup for each vaccine group. A non-inferiority test will be used to determine if the immune response elicited by NmVac4 A/C/Y/W-135-DT™ is not less than a specified difference in percent seroconversion from the licensed control vaccine. Participants will attend a screening visit up to 6 weeks prior to vaccination (day 0), then will attend study visits for 4 weeks. There will be a study phone call at days 2-3, then a post-study call to subjects to assess safety at 26 weeks.

• Study Type: Interventional
• Enrollment (Actual): 525
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Greenbelt, Maryland, United States, 20770
      • Mid Atlantic Urology Associates LLC
    • Pasadena, Maryland, United States, 21122
      • Chesapeake Research Group
    • Towson, Maryland, United States, 21204
      • IRC Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria (IC):

• Participant is willing and able to give informed consent and comply with all aspects of the evaluation after the nature of the study is explained.
• Male or female, aged 18 to 55 years old
• In general good health with no significant chronic or acute conditions that would interfere with immune response or expected Adverse Event (AE) evaluation in the opinion of the investigator as determined by Medical history and/or History-directed physical examination
• Abstinence or use of effective contraception by the participants or their partners during the trial and continuing for four weeks after vaccination will be required for males or female participants of child bearing potential.
• Able (in the opinion of the investigator) to comply with all study requirements.

Exclusion Criteria (EC):

• Unwilling or unable to understand study requirements and give written informed consent for the study.
• Prisoners.
• History of Guillain-Barré syndrome (GBS).
• Pregnancy (confirmed by positive pregnancy test) or lactation.
• Previous diagnosis of laboratory confirmed meningococcal disease.
• Previous meningococcal meningitis vaccination in the last five years
• Laboratory abnormalities that are considered Grade 2 or higher (based on AE, ranges as described in the protocol appendix) that in the opinion of the Investigator would raise safety concerns for participation in the study or interfere with evaluation of study objectives, or abnormalities >2 times the Upper Limit of Normal range (ULN).
• Known or suspected autoimmune or connective tissue disorders, including rheumatoid arthritis and congenital or acquired immunodeficiency. Does not include mild to moderate seasonal/perennial allergies treated with over the counter antihistamines.
• Use of systemic immunosuppressive drugs or therapy within 6 months prior to study enrollment, not including topical or inhaled steroids/cytotoxic agents. Includes anti-cancer chemotherapy, radiation, and long term systemic corticosteroid therapy. History of anaphylactic shock, severe asthma, urticaria, or other allergic or hypersensitivity reactions following vaccination or known hypersensitivity to any vaccine component.
• Received blood, blood products, plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months.
• Use of systemic antibiotics within 72 hours prior to study enrollment.
• History of cirrhosis or hepatitis.
• Known bleeding disorder or condition associated with a prolonged bleeding time.
• Positive results of testing for hepatitis B surface antigen (HepBsAg), Hepatitis C or HIV-1 or HIV-2 antibodies. Known or suspected HIV or Hepatitis B or C infection.
• Positive results of drug screen that cannot be explained by use of approved prescription medication (amphetamine, tetrahydrocannabinol (THC), cocaine). Current (past 30 days) heavy smokers (greater than or equal 1 pack per day).tetrahydrocannabinol
• Received another investigational product within the last 30 days. Investigational product may be a drug, vaccine, medical device or medical procedure.
• History of significant head trauma, alcohol or substance abuse or other medical illnesses that could cause a neurological deficit (e.g., cerebro-vascular disease).
• Medication or alcohol use that, in the opinion of the Investigator, may influence or bias the clinical outcome of the trial.
• History of any serious chronic medical or psychiatric illnesses or condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
• History of chronic or severe headaches, myalgia, arthralgia, malaise, fatigue or other systemic disorder commonly observed as AEs for licensed meningococcal vaccines.
• Currently experiencing a cold, flu or other acute illness (subject may be deferred until after recovery).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Test Vaccine; NmVac4-A/C/Y/W-135-DT™ conjugate vaccine	Biological: Test Vaccine; NmVac4-A/C/Y/W-135-DT™ conjugate is a vaccine in liquid form composed of purified polysaccharides (PS) conjugated to diphtheria toxoid. Single intramuscular 0.5 mL dose contains 4 µg each of Serogroup A, C, W-135, and Y PS conjugated to approximately 26 µg total diphtheria toxoid.; Other Names: NmVac4-A/C/Y/W-135-DT™; meningococcal meningitis conjugate vaccine, quadrivalent
ACTIVE_COMPARATOR: US Licensed Vaccine; Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine	Biological: US Licensed Vaccine; Meningococcal (Groups A,C,Y,W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine 0.5 mL dose, intramuscular. Single dose contains 4 µg each Serogroup A, C, W-135 and Y conjugated to approximately 48 µg total diphtheria toxoid.; Other Names: meningococcal meningitis conjugate vaccine, quadrivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroresponse (Percent Seroconversion).	Rise in antibody titers in serum at 4 weeks after vaccination, compared to baseline titer for meningococcal serogroups A, C, Y, and W-135. Serum Bactericidal Assay with human complement: Antibody titer ≥1:8 for subjects with titer <1:8 at baseline or a 4-fold rise in antibody levels.	Week 4 after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited Adverse Events From Diary Cards	Local and systemic rates from Diary Cards filled by the participants.	Day 0 to Day 7 after vaccination
Non Solicited Adverse Events	Non solicited local and systemic adverse Event (AE) rates throughout the course of the study, based on laboratory test results, vital signs, examination and questioning the subjects.	up to 6 months

Collaborators and Investigators

• Sponsor: JN-International Medical Corporation
• Investigators: Principal Investigator: Alberto Yataco, MD, IRC Clinics,; Principal Investigator: Jeffrey E Atkinson, MD, Chesapeake Research Group; Principal Investigator: Myron I Murdock, MD, Mid Atlantic Urology Associates LLC

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: July 9, 2013
• First Submitted That Met QC Criteria: July 11, 2013
• First Posted (ESTIMATE): July 12, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 23, 2015
• Last Update Submitted That Met QC Criteria: April 16, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Meningitis; Meningococcal vaccine; Central Nervous System Infections; toxoid; conjugate vaccines
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Corynebacterium Infections; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Neisseriaceae Infections; Diphtheria; Meningitis, Meningococcal; Meningitis; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: JN-NM-002