NmVac4-A/C/Y/W-135-DT™ conjugate vaccine

Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine

Test Vaccine

US Licensed Vaccine

Total

Sex: Female, Male

Race/Ethnicity, Customized

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.

NmVac4-A/C/Y/W-135-DT™ conjugate vaccine
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.

Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine
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.

Seroresponse (Percent Seroconversion).

Local and systemic rates from Diary Cards filled by the participants.

Test Vaccine - Male

Test Vaccine - Female

US Licensed Vaccine - Male

US Licensed Vaccine - Female

Solicited Adverse Events From Diary Cards

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.

Non Solicited Adverse Events

Overall Study

Regulatory Affairs Director

Meningococcal Meningitis

Meningococcal Infections

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.

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.

Mid Atlantic Urology Associates LLC

Chesapeake Research Group

IRC Clinics

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

JN-International Medical Corporation

Children born to mothers, who have accepted to participate, will be randomised to either intervention group or to the control group at birth. Block-randomisation stratified by hospital, gender and gestational age (≥37 weeks of gestation vs. < 37 weeks of gestation) will be performed electronically just before vaccination by the overall study electronic case report system (e-crf).
Children randomised to the BCG vaccination group will receive an intradermal BCG vaccine (Statens Serum Institute "CG vaccine" in the standard dose 0.05 ml in the upper, lateral part of the arm of the child by a specially trained midwife or a study physician.

Control children will be treated as usual, since no suitable placebo exists.

BCG-vaccine

Control Children

Gender of the child. In multiple births: gender of the first born child.

All three study sites are situated in Denmark.

Region of Enrollment

Premature birth

To test that infants who get the BCG vaccine at birth experience 20% fewer hospitalisations in early childhood than non-BCG-immunised infants.

Control Children (no Intervention)

All-cause Hospitalisations

To test that infants who get the BCG vaccine at birth are prescribed less antibiotics during early childhood than non-BCG-immunised infants. Use of antibiotics was defined as one or more precriptions of systemic antibiotics (ATC groups J01, J02, J05, all subgroups inclusive).

Antibiotics

To test if BCG vaccination within 7 days after birth influence the risk of atopic dermatitis defined by clinical examination at 13 months of age using "scoring atopic dermatitis (SCORAD)" or by parental report of physician diagnosed atopic dermatitis in the telephone interview at 13 months of age.

Atopic Dermatitis

Number of participants with specific IgE (Phadiatop Infant) above the clinical cut-of level of 0.35.

Specific IgE

To test that infants who get the BCG vaccine at birth respond in weight.The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.

Standardized Weight at 13 Months

To test that premature infants with gestational age less than 37 weeks who get the BCG vaccine at birth have unaffected psychomotor development measures: ASQ: Ages and stages questionnaire - a parent reported questionnaire that measures child psychomotor development. Total range of ASQ score: 0 to 300 points. Higher scores indicate higher level of psychomotor development.

Psychomotor Development in Premature Infants

To test that infants who get the BCG vaccine at birth has unaffected coverage with the subsequent 3rd diphtheria, tetanus, acellular pertussis, polio, Haemophilus influenzae type b (DTaP-IPV-Hib) vaccination scheduled to 12 months of age according to the Danish child vaccination programme. Since we did not expect all children to get their immunizations exactly at 12 months of age, the children were followed up until 13-months of age.

DTaP-IPV-Hib Vaccination Coverage at 12 Months of Age

The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.

Standardized Weight, Length and Head Circumference of Premature Children at 13 Months

Number of participants diagnosed with episodic viral wheeze by a physician and treated with anti-asthmatic medicine according to the telephone interview.

Episodic Viral Wheeze

Number of participants with food allergy diagnosed by a physician and mentioned in the telephone interview at 13 months of age

Food Allergy

To test if infants who get the BCG vaccine at birth respond in length. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.

Length at 13 Months of Age

To test if infants who get the BCG vaccine at birth respond in head circumference. The Z-score indicates the number of standard deviations away from the mean weight-for-age of the WHO anthropometric reference population (http://www.who.int/childgrowth/standards/en/). A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.

Standardized Head Circumference at 13 Months of Age

To test that infants who receive the BCG at birth respond in thymic gland size defined by ultra sound examination. First, the thymus gland was identified in a horizontal scanning plane and the largest transverse diameter of the thymus was obtained. Second, in a sagittal scanning plane, the area of the largest lobe was assessed. Both measurements were obtained twice, and in case of more than 15% difference, both measurements were repeated. The mean of the two measurements were multiplied and defined as the thymic index.

Thymic Gland Size at 3 Months of Age

To test if infants who receive the BCG at birth respond in leucocyte count (white blood cell count) measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).

Leucocyte Count 4 Days After Randomisation/Vaccination

To test if infants who receive the BCG at birth respond in monocyte count measured as geometric mean (GM) cell concentrations (GM*10^9 cells/L).

Monocyte Count 4 Days After Randomisation/Vaccination

To test that infants who receive the BCG at birth respond in interferon-gamma response upon stimulation with BCG. The interferon gamma response was defined as a value above the cut-off value of 107 pg/ml.

Interferon Gamma Response

To test the tetenus antibody response in BCG-vaccinated vs. non-BCG vaccinated children following routine immunisation against tetanus at 3, 5 and 12 months of age in blood samples obtained 13 months of age.

Number of Participants With Antibody Concentration (AC) Against Tetanus of > 0.1 IU/mL

To test that Danish infants who get the BCG vaccine at birth experience less events of common cold until 13 months of age than non-BCG-immunised infants.

Number of Events of Common Cold

To test that Danish infants who get the BCG vaccine at birth get less pneumonia at 13 months of age than non-BCG-immunised infants.

Number of Events of Pneumonia

To test that Danish infants who get the BCG vaccine at birth get less febrile episodes at 13 months of age than non-BCG-immunised infants.

Number of Events of Febrile Episodes

To test that Danish infants who get the BCG vaccine at birth develop less episodes with diarrhoea and vomiting at 13 months of age than non-BCG-immunised infants.

Number of Events With Diarrhoea and Vomiting

To test that Danish infants who get the BCG vaccine at birth develop less acute otitis media at 13 months of age than non-BCG-immunised infants.

Number of Events of Acute Otitis Media

To test that Danish infants who get the BCG vaccine at birth develop less febrile convulsions at 13 months of age than non-BCG-immunised infants.

Number of Events of Febrile Convulsions

After parents having made the decision about whether to accept vaccination of their newborn through participation in The Danish Calmette Study, O'Connor's Decisional Conflict Scale was used to identify decisional conflicts. The score ranges from 0 (no decisional conflict) til 100 (maximum decisional conflict). Scores lower than 25 are associated with implementing decisions; scores exceeding 37.5 are associated with decision delay or feeling unsure about implementation; so a low score reflects a low level of doubt about the decision about participation/decline participation in the trial, and a high score reflects a high level of doubt.

Mothers who decided to let their child participate in the study

Participating Mothers

Mothers who decided not to let their child participate in the study

Declining Mothers

Decisional Conflict Scale Score

To test that the use of telephone and internet was acceptable in the study population using the Quality of Informed Consent (QuIC) questionnaire. The questionnaire was divided into six categories; five on study comprehension and one on satisfaction with the information process. The items in the first five categories could be answered with "yes", "no" or "do not know". The last category was rated on a 7-point Likert scale, with 1 being "very dissatisfied" and 7 being "very satisfied". The primary outcome was the sum of the score for comprehension items and satisfaction items. Comprehension items were scored 1 point for each correct answer and 0 points for each incorrect answer. Satisfaction items were scored as rated on the 7-point Likert scale. Total score ranged from 7 to 69 points, comprehension score from 0 to 20 points and satisfaction score from 7 to 49 points. The higher score, the better comprehension and satisfaction.

Randomized to receive information about the study by telephone

Telephone

Randomized to receive information about the study by standard face-to-face consultation.

Face-to-face

Quality of Communication and Information

Lone Graff Stensballe, Research leader, Pediatrician, PhD

Prospective

Single-blind

Clinical

Trial

Intervention

BCG-vaccine (SSI)

Rigshospitalet

Hvidovre Hospital

Kolding Sygehus

Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children.

Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children. A Prospective, Randomised, Clinical Trial.

Lone Graff Stensballe

MD, PhD

Hvidovre University Hospital

Danish National Research Foundation

Research Center for Vitamins and Vaccines (CVIVA)

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 Serogroup A, C, W-135, Y PS conjugated to approximately 16 µg total diphtheria toxoid.

meningococcal meningitis conjugate vaccine, quadrivalent

Meningococcal (Groups A,C,Y and W-135-DT) Polysaccharide Conjugate Vaccine 0.5 mL dose, intramuscular. Single dose contains 4 µg each Serogroup A, C, W-135, Y PS conjugated to approximately 48 µg total diphtheria toxoid.

Kings Cardiology Group

Safety Study of Group A, C, Y & W-135 Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine for Meningitis

A Double-Blind, Randomized, Controlled, Two Arm Phase 1 Clinical Trial of the Safety and Immunogenicity of Group A, C, Y & W-135 Meningococcal Polysaccharide DT Conjugate Vaccine: NmVac4-A/C/Y/W-135-DT™

local and systemic rates throughout the course of the study

Subjects who did receive PEP following pertussis exposure

Subjects who did not receive PEP following pertussis exposure

Enrolled subjects involved in a pertussis exposure who received no antibiotic post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)

No PEP

Enrolled subjects involved in a pertussis exposure who received post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)

Antibiotic PEP

Defined as a positive nasopharyngeal culture or PCR for B. pertussis at any time point, a two-fold rise in the anti-PT IgG titer between acute and convalescent sera, or a single acute or convalescent anti-PT IgG titer of ≥94 EU. Post hoc, a modified definition was devised because of concern that the serologic criteria used in the primary definition might actually represent acquisition of pertussis infection prior to the intervention. The modified definition of pertussis excluded an acute anti-PT IgG titer of ≥94 EU and an acute nasopharyngeal swab that was positive for B. pertussis by PCR.

Evidence of Pertussis Infection in Each PEP Arm, Defined Using Clinical, Microbiologic, or Serologic Criteria.

Dr. Thomas R. Talbot

Pertussis

Azithromycin 1000mg po x 1, then 500mg po Q day for 4 days; TMP-SMX DS one BID for 14 days

diphtheria/vomito

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

Bacille Calmette Guérin Immunisation at Birth and Childhood Morbidity in Danish Children.

Safety Study of Group A, C, Y & W-135 Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine for Meningitis

Vanderbilt Pertussis Exposure Study: PEP in Vaccinated Healthcare Workers Following Pertussis Exposure

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