Non Inferiority Trial of Locally Manufactured Meningococcal ACWY Vaccine 'Ingovax ACWY' in Bangladesh.
Condition: Meningococcal Vaccine
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This study will be a randomized observer -blinded controlled non-inferiority study to
      evaluate and compare the immunogenicity of locally produced Ingovax ACWY with Quadri Meningo
      on a total of 88 healthy adult participants (18-45 years of age). 44 participants will
      receive locally produced Ingovax ACWY and 44 participants of comparator groups will receive
      Quadri Meningo which is produced by BiO-MeD Private Limited. Vaccination will be done in Day
      0 following the screening and pre-immunization blood sample collection and post-immunization
      blood will be collected at Study Day 30. Follow- up by home visit will be carried out from
      Study day 1-6 and clinic follow-up is scheduled upto Study day 90. The hypothesis of this
      study is: locally produced subcutaneous Meningococcal vaccine Ingovax ACWY is non inferior
      and immunogenic among adults in Bangladesh as compared to Quadri Meningo.
    

Detailed description: 
      Protocol Title: A randomized observer-blinded controlled non-inferiority trial to evaluate
      the immunogenicity of locally manufactured Meningococcal ACWY vaccine 'Ingovax ACWY' in
      Bangladeshi healthy adults.

      Background:

        1. Burden:

           Meningococcal disease is an infectious disease caused by Neisseria meningitidis or
           meningococcus, which may present clinically as meningococcemia or meningitis, or
           presence of both features. Meningococcal meningitis causes inflammation of the membranes
           covering the brain and spinal cord. Meningococcal meningitis or meningococcemia is a
           life-threatening disease. It affects adults, adolescents and children as well. Every
           year more than 1.2 million people are affected by meningitis. It causes approximately
           120,000 deaths globally each year. It can cause severe brain damage and is fatal in 50%
           of cases if untreated. According to a review article on meningococcal disease in Asia,
           results from four retrospective hospital-based studies conducted in Bangladesh showed
           that N. meningitidis present up to 35% of positive cultures in all ages, and up to 18%
           in children aged <2 years with bacterial meningitis. At the International Centre for
           Diarrhoeal Disease Research in Bangladesh, of 628 blood and CSF samples, N. meningitidis
           was detected in 24•8% (n=156), of which 97•7% were serogroup A and the rest 2.3% were
           serogroup B between 1999 and 2006. Of the 156 N. meningitidis isolates, 89 (57%) were
           from blood and 67 (43%) from CSF. Meningococcemia occurs without meningitis in 5% to 20%
           among the meningococcal infections. Globally the case-fatality ratio of meningococcemia
           is up to 40%.

           Despite of prompt diagnosis and the availability of appropriate treatments, the diseases
           is still a threat to the people. In spite of getting antibiotic in time, one in ten
           infected people die within 2 days of their first symptoms, one in four survivors is left
           with long-term disabilities such as loss of limb (s), deafness, nervous system problems,
           or brain damage. The disease can be transmitted as long as the symptoms persist or until
           24 hours of effective treatment have been started. Carriers without symptoms can
           transmit the disease for about 6 months. Moreover, the disease can easily spread from
           person to person by respiratory droplets of sneezing or coughing or by sharing utensils.

        2. Knowledge gap:

           Several different bacteria can cause meningitis. Neisseria meningitidis is the one with
           the potential to cause large epidemics. There are 12 Serogroups of N. meningitidis that
           have been identified, 6 of which (A, B, C, W, X and Y) can cause epidemics. But only a
           single dose of vaccine can prevent this deadly disease. Meningococcal Polysaccharide
           Vaccine of four serogroups A, C, W and Y that can protect from meningococcal meningitis
           and other associated diseases. It is a highly immunogenic and tolerable meningococcal
           vaccine to prevent meningococcal disease. World Health Organization recommends that
           countries with a moderate or high rate of disease or with frequent outbreaks should
           routinely vaccinate. Currently there is no locally manufactured Meningococcal vaccine
           available in Bangladesh. The results of this study will provide information regarding
           the immunogenicity of the locally manufactured meningococcal vaccine.

        3. Relevance:

           The study of this locally manufactured Meningococcal Vaccine (Incepta) 'Ingovax ACWY'
           among adults will be able to give us information regarding the safety and immunogenicity
           of the vaccine. To get registration of this own bulk and finished product, Incepta
           intends to conduct clinical trials in human. Incepta has already conducted two
           Pre-clinical Studies at Reliance clinical research" in Mumbai, India. Toxicological
           evaluation of Meningococcal ACWY Vaccine (Ingovax) was conducted in Swiss albino mice
           and Sprague Dawley rats. No mortality or morbidity was observed in any of the animals in
           the control or the treated groups. No treatment related abnormal changes were observed
           in Clinical Signs, Body Weight, Food Consumption and Ophthalmological Examination. In
           the light of the above findings, No Observed Adverse Effect level (NOAEL) of
           Meningococcal ACWY Vaccine (Ingovax) is 50µg per rat or mouse. So, after successful
           completion of Preclinical study, the non-inferiority trail with this vaccine needs to be
           carried out with innovator product and move forward to licensure in Bangladesh.
           Currently there is no locally manufactured Meningococcal vaccine available in
           Bangladesh. Once this clinical trial is complete, it will then proceed for registration
           and licensure in Bangladesh. Thus the vaccine cost could be significantly reduced and
           save a large amount of foreign currency of Bangladesh Government.

           Hypothesis (if any): Locally produced subcutaneous Meningococcal vaccine Ingovax ACWY is
           non inferior and immunogenic among adults in Bangladesh as compared to Menomune® -
           A/C/Y/W-135.

           Objectives: The objective of this study is to

           Primary Objective:

           1.To evaluate and compare the immunogenicity of Ingovax ACWY' with Quadri Meningo in
           healthy adults in Bangladesh.

           Secondary Objective:

           1. To evaluate and compare the safety of locally produced Ingovax ACWY with Quadri
           Meningo.

           Methods:

           This will be a randomized observer -blinded controlled non-inferiority study on a total
           of 88 healthy adult participants (18-45 years of age). 44 Ingovax ACWY'0.5 ml (Test
           group) and 44 Quadri Meningo 0.5 ml (Comparator Group).

           Outcome measures/variables: To evaluate and compare the immunogenicity and safety of
           locally produced Ingovax ACWY' with Quadri Meningo vaccine.

           Primary end points:

           1. Assessment of proportion of participants showing seroconversion (defined as a ≥4-fold
           rise in SBA titers) vaccinated with either Ingovax ACWY Vaccine (Incepta) or Quadri
           Meningo vaccine (BiO-MeD Private Limited). The non-inferiority margin will be 10%.

           Secondary end points:

             1. To compare the GMTs between vaccines, and GMT ratios.

             2. Number of immediate reactions reported within 30 minutes after vaccination

             3. Number of solicited adverse events (prelisted in the participant's memory aid)
                occurring up to 7 days following vaccination.

             4. Number of unsolicited AEs up to 28days after vaccination.

             5. Occurrence of serious adverse events (SAEs) throughout the trial
    

Intervention name(s): Ingovax ACWY; Quadri Meningo
Intervention type(s): Biological; Biological
Intervention description(s): The pharmaceutical company in Bangladesh is now currently marketing meningococcal vaccine of Yuxi Walvax Biotechnology Co. Ltd which is filled finish by Incepta Vaccines Ltd. This fill finish meningococcal vaccine is already registered and licensed in Bangladesh. However, at present, no locally produced meningococcal vaccine is available in Bangladesh. Once this clinical trial is completed, it will then proceed for registration and licensure in Bangladesh. Ingovax ACWY is a freeze-dried preparation of the group-specific polysaccharide antigens from Neisseria meningitidis Group A, Group C, Group Y and Group W135. When reconstituted, the vaccine is a clear, colorless sterile solution for subcutaneous use.; Meningococcal polysaccharide vaccine Quadri Meningo vaccine manufactured by BiO-MeD Private Limited. Quadri Meningo [Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined] is a freeze-dried preparation of the Group-specific polysaccharide antigens from Neisseria meningitidis, Group A, Group C, Group Y, and Group W-135. After reconstitution with diluent, the vaccine is a clear colourless liquid.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Eligible participants will be assigned to receive the Ingovax ACWY Vaccine and Quadri Meningo Vaccine, in a 1:1 ratio across the target population according to the randomization schedule. 44 participants will receive locally produced Ingovax ACWY and 44 participants of comparator groups will receive Quadri Meningo which is produced by BiO-MeD Private Limited.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Meningococcal Vaccine; Ingovax ACWY; adults; Bangladeshi; immunogenicity