Weuphoria

13-valent pneumococcal polysaccharide conjugate vaccine.

The vaccine is supplied in a single-dose prefilled syringe with 0.5 mL suspension for intramuscular injection. Each dose (0.5 mL) of the vaccine contains: See Table 1.

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The 13-valent Pneumococcal Polysaccharide Conjugate Vaccine (PCV13-TT) is formulated by compounding the capsular polysaccharide antigen of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, individually conjugated to tetanus toxoid carrier protein. The individual polysaccharides are extracted from the cultures of Streptococcus pneumoniae, and purified through centrifugation, precipitation, and ultrafiltration. The polysaccharides are chemically activated and derivatized, and then conjugated to tetanus toxoid carrier protein to form the glycoconjugate, with aluminum phosphate as adjuvant. The vaccine should be shaken well to obtain a homogenous milky white suspension. During storage, a white deposit and clear supernatant might be observed due to adjuvant precipitation.
Active substances: capsular polysaccharides of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F conjugated to tetanus toxoid carrier protein.
Excipients/Inactive Ingredients: Sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, and aluminum phosphate.

Pharmacology: PHARMACODYNAMICS/PHARMACOKINETICS: Not applicable.
CLINICAL TRIALS: In China, the pivotal phase III clinical trial of PCV13-TT was a randomized and blinded non-inferiority study comparing to Prevnar. This study evaluated the immunogenicity and safety of PCV13-TT and Prevnar (7 serotypes) in 2760 subjects 2 through 71 months of age (at least 6 weeks of age). A total of 1040 infants aged 3 months were randomized in a 1:1 ratio as study group and the control group, with PCV13-TT or Prevnar given at 3, 4, 5, and 12-15 months of age, respectively; for 520 infants aged 2 months (at least 6 weeks of age), PCV13-TT was vaccinated at 2, 4, 6, and 12-15 months of age. 1200 Children of 7 through 71 months of age, including children 7 months through 11months of age, 12 months through 23 months of age and 24 months through 5 years of age (prior to the 6^th birthday) who were naïve to pneumococcal conjugate vaccine, were split into three age groups with each containing 400 subjects randomized in a 1:1 ratio given 3, 2 or 1 dose of PCV 13-TT or Prevnar, respectively, according to the age-appropriate schedules in Table 8 and Table 9. Enzyme-linked immunosorbent assay (ELISA) was utilized to detect the IgG antibody concentration in all serum samples collected from each group; additionally, a subsets of sera randomly obtained from 100 subjects in each age group for PCV13-TT and Prevnar, totaling 900, were tested by opsonophagocytic assay (OPA) to measure the ability of serotype-specific functional antibodies to eliminate corresponding pneumococci by promoting complement-mediated phagocytosis.
The main target population of the pivotal trial were infants of 2 and 3 months of age (at least 6 weeks of age). For immunogenicity, the PCV13-TT (3 months) group was compared with the Prevnar (3 months) in the first place, followed by the comparison between PCV13-TT (2 months) group versus Prevnar (3 months) group and then the comparison between the PCV13-TT (2 months) versus the PCV13-TT (3 months) group. The immunogenicity endpoints include the percentage of subjects with IgG antibody concentration was ≥ 0.35 μg/mL (positive rate) and the geometric mean concentration (GMC) of serotype-specific IgG antibody one month post the final dose of primary series and booster dose, as well as the percentage of subjects with vaccine serotype-specific OPA titer was ≥ 1:8 (positive rate) and OPA geometric mean titer (GMT) one month post the final dose of primary series and booster dose.
The non-inferiority comparison was performed for the immune responses of 7 common serotypes between PCV13-TT and Prevnar. For the 6 additional serotypes, if the lower limits of 95% CI for IgG antibody positive rate in study group achieved ≥ 70%, superiority assessment was then performed to compare the immune responses to 6 additional serotypes and corresponding serotypes in the control group; meanwhile, the 6 additional serotypes in study group were compared with the serotype with the lowest response among all the 7 common serotypes in the control group to determine the non-inferiority. The non-inferiority can be established either through demonstrating the lower limit of 97.5% CI for the difference of positive rate between groups (study group - control group) were > -10%, or the lower limit of 97.5% CI for IgG geometric mean concentration (GMC) ratio (study group/control group) was > 0.5; whereas the superiority can only be demonstrated when both lower limit of 96% CI for the difference of positive rates between groups (study group - control group) > 0, and the lower limit of 95% CI for the IgG GMC ratio (study group/control group) >1. The results are shown as follows: In subjects aged 3 months, after primary series (3 doses), the IgG antibody was compared between the PCV13-TT group and the Prevnar group. Six out of seven common serotypes met the non-inferiority criteria with the exception of 6B; the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT group were non-inferior to the serotype with the lowest response among all the 7 common serotypes in the Prevnar group.
In subjects aged 3 months, after complete series (4 doses), the IgG antibody were compared between the PCV13-TT group and the Prevnar group. All 7 common serotypes met the non-inferiority criteria; the 6 additional serotypes reached the superiority threshold; besides, the 6 additional serotypes in the PCV13-TT group were non-inferior to the serotype with the lowest response among all the 7 common serotypes in the Prevnar group.
In subjects aged 2 months (at least 6 weeks of age), after primary series (3 doses), the IgG antibody was firstly compared between the PCV13-TT (2 months) group and the Prevnar (3 months) group, showing that all 7 common serotypes met the non-inferiority criteria and the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT (2 months) group were non-inferior to the serotype with the lowest IgG response among all 7 common serotypes in the Prevnar (3 months) group. The IgG antibody was then compared between the PCV13-TT (2 months) group and the PCV13-TT (3 months) group. Twelve out of the thirteen serotypes met the non-inferiority criterion with the exception of serotype 5.
In subjects aged 2 months (at least 6 weeks of age), after complete series (4 doses), the IgG antibody were firstly compared between the PCV13-TT (2 months) group and the Prevnar (3 months) group. All 7 common serotypes met the non-inferiority criteria and the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT (2 months) group were non-inferior to the serotype with the lowest IgG response among all 7 common serotypes in the Prevnar (3 months) group. The IgG antibody was then compared between the PCV13-TT (2 months) group and the PCV13-TT (3 months group). All the 13 serotypes met the non-inferiority criteria.
The testing results of OPA antibody demonstrated that, all 13 serotypes of PCV13-TT were capable of inducing anti-pneumococcal OPA antibody in all age groups in the study group.
The immunogenicity data from subjects 2 months (at least 6 weeks of age) through 71 months of age are shown in Table 2 to Table 7. (See Tables 2, 3, 4, 5, 6, and 7.)

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The vaccine is indicated for use in infants and children 6 weeks through 5 years of age (before the 6^th birthday).
The vaccine elicits immune responses in recipients following immunization, and is indicated for the prevention of invasive disease caused by 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) of Streptococcus pneumoniae.
The vaccine does not protect against diseases caused by Streptococcus pneumoniae serotypes that are not contained in the vaccine.

Since this product is a suspension containing an adjuvant, shake vigorously immediately prior to use to obtain a homogenous, white suspension in the vaccine container. This product is for intramuscular injection only. The preferred sites for injection are the anterolateral aspect of the thigh in infants and the deltoid muscle of the upper arm in toddlers and children. the vaccine should not be injected in and/or near the areas where nerve trunks and/or blood vessels may locate.
Vaccination schedules for infants and toddlers: The product is to be administered as a four-dose series at 2, 4, 6, and 12-15 months of age or 3, 4, 5, and 12-15 months of age, respectively, as described in Table 8 and Table 9. (See Tables 8 and 9.)

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For children 7 months through 5 years of age who have not received the product, the catch-up schedule in Table 10 applies: See Table 10.

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Overdose with PCV13-TT is unlikely due to its presentation as a single-dose vial or a single-dose pre-filled syringe. No overdose data are available for the product in recipients.

Hypersensitivity to any component of the product, including active substances, excipients, or tetanus toxoid, etc.

Do not vaccinate via intravenous route or by gluteal intramuscular injection, and ensure the syringe needle is not puncturing blood vessel during inoculation.
Check if the package, container, label, appearance and expiration date of the vaccines are in compliance with corresponding requirements before administration. Do not use the vaccine in case that any crack is observed in the container, loosened stopper, detached label, foreign particle(s) or discoloring inside the container, etc.
Use immediately after unsealing. A single human dose shall be used up each time according to prescribing information.
The vaccination should be postponed in case of fever, acute disease, and acute attack of chronic disease.
Appropriate monitoring and medical care rescue measures should be readily available in case of occurrence of rare hypersensitivity reactions during vaccination. If allergic reactions occur after vaccination, go to the vaccination site or hospital in time.
Cautions should be taken for vaccination in recipients with thrombocytopenia, any coagulopathy or those who are receiving anticoagulant treatment.
Given that no safety and immunogenicity data are available for PCV13-TT in immunocompromised individuals (e.g., malignancy or nephrotic syndrome), vaccination in this special group should be considered on an individual basis.
Under no circumstances shall the tetanus toxoid contained in the vaccine replace the routine immunization of tetanus vaccine or tetanus-containing vaccine.
This product cannot guarantee all recipients can be protected from any diseases caused by Streptococcus pneumoniae.
Use in Children: Preterm infants should be monitored for the potential risk of apnea during primary series. For preterm infants under hospitalization (gestational age ≤ 30 weeks at birth) vaccinated with PCV13-TT according to the recommended immunization schedule, at least 48 hours of monitoring should be considered. Given the benefit of vaccination in preterm infants, discontinued or deferred vaccination of the product is not recommended.
The use of PCV13-TT does not replace the use of 23-Valent Pneumococcal Polysaccharide Vaccines in children ≥ 24 moths of age with conditions such as sickle cell disease, asplenia, HIV infection, chronic illness, or those who are immunocompromised.

Pregnancy: No data are available for using the product in pregnant women.
Lactation: Whether this product is excreted into human milk remains unknown.

Clinical Trials for PCV13-TT: Two clinical trials (phase I and III) of the vaccine (PCV13-TT) were conducted in China, including 120 and 2760 subjects, respectively; among all subjects (2880), 1754 have been vaccinated with at least one dose of PCV13-TT. The safety observations were conducted in a systematic fashion for all subjects, starting from the first dose of vaccination, and the safety observation lasted for 30 days post each dose of vaccination. For a majority of subjects excluding the dropout, the long-term safety observation period started from the first vaccination till 180 days post the last dose of vaccination (after complete series).
Summary: The incidence rates of adverse reactions reported in clinical trials, according to the guidance on classifications of adverse events recommended by The Council for International Organizations of Medical Sciences (CIOMS), are classified as: very common (≥ 10%), common (≥ 1% to < 10%), uncommon (≥ 0.1% to < 1%), rare (≥ 0.01% to < 0.1%) and very rare (< 0.01%). The safety data for the primary series of PCV-13 collected from both phase I and phase III clinical trials of all subjects are summarized as follows: Systemic adverse reactions: Very common: fever, diarrhea.
Common: crying, coughing, nausea/vomiting, fatigue/somnolence, allergic reaction.
Uncommon: myalgia.
Local adverse reactions: Very common: redness.
Common: swelling, pain, induration.
Uncommon: pruritus.
Rare: rash (vaccination site).
Serious adverse reactions: One case of serious adverse event (SAE) was reported during the primary series in the 3-months age group. This SAE was reported to be fever and considered to be possibly related to PCV13-TT. Other serious adverse events were adjudicated to be irrelevant to PCV13-TT.
Adverse Reactions in Phase III Clinical Trial: The incidence rates and severity of solicited adverse reactions: The incidence rates and severity of solicited adverse reactions post primary and booster immunization in phase III clinical trial of PCV13-TT comparing to the comparator vaccine (Pneumococcal 7-valent Conjugate Vaccine [Diphtheria CRM197 Protein], referred to as Prevnar) are summarized in Table 11 and Table 12. (See Tables 11 and 12.)

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Incidence rates and severity of unsolicited adverse reactions: The incidence rates of unsolicited adverse reactions for PCV13-TT were 0.06%-0.73% with most episodes being grade 1 in severity. The documented symptoms include: nasal obstruction, rhinorrhea, nasopharyngitis, upper respiratory tract infection, oral ulcer, abdominal pain, abdominal distension, decreased appetite, hyperhidrosis, increased tearing and eye discharge and red eyelids.

No concomitant immunization data are available either inside or outside of China for the product. During the phase III clinical trial of the product, the interval between vaccination of the product and any other diphtheria, tetanus and acellular pertussis (DTaP)-containing vaccine was ≥ 10 days. No adverse impact of DTaP-containing vaccine was observed on the immunogenicity of PCV13-TT under the indicated immunization interval.

INCOMPATIBILITIES: This vaccine should not be mixed with other medicinal products considering that no compatibility studies have been conducted.

Transport and store refrigerated at 2°C to 8°C, protect from light.
DO NOT FREEZE. Discard if the vaccine has been frozen.
SHELF-LIFE: The shelf life of the vaccine is 24 months.

Vaccines, Antisera & Immunologicals

J07AL02 - pneumococcus, purified polysaccharides antigen conjugated ; Belongs to the class of pneumococcal bacterial vaccines.

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