An Open-Label Controlled Phase I/III Study to Evaluate the Safety and Immunogenicity of Pneumococcal 7-Valent Conjugate Vaccine [DIPHTHERIA CRM197 PROTEIN] (PrevenarTM) in Healthy Infants
An Open-Label Controlled Phase I/III Study to Evaluate the Safety and Immunogenicity of Pneumococcal 7-Valent Conjugate Vaccine [DIPHTHERIA CRM197 PROTEIN] (PrevenarTM) in Healthy Infants
This study is a combination of a Phase I and Phase III study design. The Phase I portion is an open-label, controlled study to evaluate the safety of 7vPnC in healthy Chinese infants. The Phase III portion is an open-label, controlled, randomized study to evaluate the safety and immunogenicity of 7-Valent Pneumococcal Conjugate Vaccine (7vPnC)in healthy Chinese infants. Both phases include a Primary Series which includes the primary 3 doses of 7vPnC and /or Diptheria and tetanus toxoids and accelular pertussis vaccine (DTaP) at about 3, 4, and 5 months of age; and a Booster Dose which includes the 4th dose of 7vPnC at 12-15 months of age.
This study is a combination of a Phase I and Phase III study design. The Phase I portion is an open-label, controlled study to evaluate the safety of 7vPnC in healthy Chinese infants. The Phase III portion is an open-label, controlled, randomized study to evaluate the safety and immunogenicity of 7vPnC in healthy Chinese infants. Both phases include a Primary Series which includes the primary 3 doses of 7vPnC and/or DTaP at about 3, 4, and 5 months of age; and a Booster Dose which includes the 4th dose of 7vPnC at 12-15 months of age. A total of 822 healthy Chinese infants will be enrolled. The study will be conducted in 2 phases: Phase I and Phase III.
Phase I: 22 healthy infants will be enrolled first and receive a dose of 7vPnC at least 7 days prior to receiving DTaP and followed up on safety for 30 days post the immunization. If there are no adverse events of specific concern considered, in the opinion of the principal investigator, related to the study vaccine (including, though not limited to, infectious and allergic reactions as described in the China Immunization Handbook) within 4 days after the first dose immunization and no serious adverse event possibly, probably or definitely related to the study vaccine within 30 days after the first dose of immunization, Phase III can be initiated and the infants in Phase I will proceed to the next dose of the Primary Series. If such events occur, a medical review will be conducted by both the investigator and the Sponsor to decide if the study can proceed.
Phase III: 800 infants will be enrolled and randomized to one of 3 groups according to the administration regimen. Group 1: 300 infants will receive the primary 3 doses of 7vPnC separately at 3, 4 and 5 months of age. Group 2: 300 infants will receive the primary 3 doses of 7vPnC concurrently with DTaP at 3, 4 and 5 months of age. Group 3: 200 infants will receive DTaP only at 3, 4 and 5 months of age. The injection site is the left upper arm deltoid for 7vPnC and the right upper arm deltoid for DTaP.
Safety Evaluation: Each infant will have an initial physical examination and history obtained at the enrollment visit and a brief physical evaluation at each subsequent visit. Following immunization, each subject will be observed in the clinic for 30 minutes and evaluated for signs or symptoms of anaphylaxis and reactions at the injection sites. The parent or legal guardian will be required to take the infant's axillary temperature on the evening of immunization and for 3 consecutive evenings following the immunization. In addition, if the parent suspects that the infant may have a fever at any time in the four days following immunization, the temperature is to be taken and recorded. Thermometers for axillary temperature use and diary cards will be supplied by Wyeth for distribution to the parents.
The parent or legal guardian of each subject will be instructed to complete a diary card for 4 days [day of immunization (day 0) and next 3 days] following each immunization. Information collected will include: the subject's axillary temperature, local reactions at the 7vPnC injection site (All subjects in Phase I of the study and Group 1 and Group 2 of Phase III) and DTaP injection site (Group 2 and Group 3 of Phase III) (tenderness, presence and size of erythema and induration/swelling) and any systemic reactions (disrupted sleep, drowsiness, decreased appetite, irritability, vomiting, diarrhea and rash not limited to the injection site) occurring days 0-3. The subject will return to clinic or be visited at home on the day after immunization (Day 1) for local and systemic reaction observation by study personnel. The parent or legal guardian will be contacted by telephone or home visit at 2 and 3 days post-immunization to collect information on local and systemic events and the information will be recorded on the source data sheet by study personnel. On, or after, the fourth day after each immunization, the study personnel will collect the diary card. The data in the diary card will be reconciled with the data in the source data sheet. If there is discrepancy, it should be clarified with the parents and recorded.
At the visit of next immunization, the interim medical history since Day 4 post last immunization will be reviewed with the parent/legal guardian. If there is any adverse event, it should be collected and recorded in the case report form. The primary source of data on adverse events will be the parent or legal guardian of each subject, as well as any medical records from a health care provider sought as a result of an adverse event. The parent/legal guardian is instructed to contact the investigators immediately for any serious adverse events.
Assessment of Immunogenicity: Up to 3ml venous blood will be collected from 55 infants in Group 1, 55 infants in Group 2 and 55 infants in Group 3 of Phase III, immediately prior to the first dose and 30-40 days after the 3rd dose to assess the immunogenicity.
Booster Dose: All infants in Phase I and Group 1 and Group 2 of Phase III will receive the booster dose of 7vPnC at 12-15 months of age. Local/systemic reactions will be observed in the same way as after the primary dose.
Assessment of Immunogenicity: Up to 3ml venous blood will be collected from the same 55 infants in Group 1 and 55 infants in Group 2 as in the Primary Series of Phase III, immediately prior to the forth dose and 30-40 days after the 4th dose to assess the immunogenicity.
The statistical analysis of the two phases will be conducted separately. The statistical analysis of the primary series is planned when all subjects have received the 1st, 2nd and 3rd dose of 7vPnC and 3 doses of DTaP or 3 doses of DTaP alone and the 30-day safety follow-up period has terminated. The analysis of the booster dose is planned when all subjects have received the 4th dose of 7vPnC and the 30-day safety follow-up period has terminated.
Inclusion Criteria:
Exclusion Criteria:'