Study To Describe The Safety, Tolerability, And Immunogenicity Of 13- Valent Pneumococcal Conjugate Vaccine Formulated In Multidose Vials When Given With Routine Pediatric Vaccines In Healthy Infants In India

• ClinicalTrials.gov Identifier: NCT03548337
• Recruitment Status: Completed
• First Posted: June 7, 2018
• Results First Posted: September 30, 2020
• Last Update Posted: September 30, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

A Phase 4 Study To Describe The Safety, Tolerability, And Immunogenicity Of 13- Valent Pneumococcal Conjugate Vaccine Formulated In Multidose Vials When Given With Routine Pediatric Vaccines In Healthy Infants In India

Condition or disease	Intervention/treatment	Phase
Vaccines	Biological: 13vPnC	Phase 4

Detailed Description:

A Phase 4, Randomized, Open-label Trial To Describe The Safety, Tolerability, And Immunogenicity Of 13- Valent Pneumococcal Conjugate Vaccine Formulated In Multidose Vials When Given With Routine Pediatric Vaccines In Healthy Infants In India

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 301 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A PHASE 4, RANDOMIZED, OPEN-LABEL TRIAL TO DESCRIBE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF 13- VALENT PNEUMOCOCCAL CONJUGATE VACCINE FORMULATED IN MULTIDOSE VIALS WHEN GIVEN WITH ROUTINE PEDIATRIC VACCINES IN HEALTHY INFANTS IN INDIA
• Actual Study Start Date: May 31, 2018
• Actual Primary Completion Date: December 20, 2019
• Actual Study Completion Date: December 20, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 13vPnC with 2-PE from a MDV; Multi Dose Vial with preservative	Biological: 13vPnC; 13vPnC MultiDose Vial with preservative compared to a Prefilled syringe containing 13vPnC without any preservative
Active Comparator: 13vPnC without 2-PE in a PFS; Pre Filled Syringe without preservative	Biological: 13vPnC; 13vPnC MultiDose Vial with preservative compared to a Prefilled syringe containing 13vPnC without any preservative

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1 [ Time Frame: Within 7 days after Vaccination 1 ]
   Local reactions were recorded daily using an electronic diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild (0.5 to 2.5 centimeters [cm]), moderate (2.5 to 7.0 cm) and, severe (greater than [>] 7 cm). Pain at injection site was graded as mild (hurt if gently touched (example, whimpers, winces, protests, or withdraws), moderate (hurt if gently touched [with crying]), and severe (caused limitation of limb movement). Participants may be represented in more than 1 row. Here, "Any" for redness, swelling and pain at injection site represents any grade of these local reactions among mild, moderate or severe.
2. Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1 [ Time Frame: Within 7 days after Vaccination 1 ]
   Systemic events included fever, decreased appetite, drowsiness(increased sleep) and irritability,were recorded daily using an electronic diary. Fever graded as:1)less than (<)38.0 degrees Celsius [C], 2)greater than or equal to(>=)38.0 degree C to 38.4 degree C, 3)38.5 degree C to 38.9 degree C, 4) 39.0 degree C to 40.0 degree C, 5) >40.0 degree C. Decreased appetite graded as: mild(decreased interest in eating), moderate(decreased oral intake), and severe(refusal to feed). Drowsiness graded as:mild(increased or prolonged sleeping bouts), moderate(slightly subdued; interfering with daily activity), and severe(disabling; not interested in usual daily activity). Irritability graded as: mild(easily consolable), moderate(required increased attention), and severe(inconsolable; crying could not be comforted). Participants may be represented in >1 row. Here,"Any" for decreased appetite, drowsiness, irritability represents any grade of these systemic reactions among mild, moderate or severe.
3. Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2 [ Time Frame: Within 7 days after Vaccination 2 ]
   Local reactions were recorded daily using an electronic diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild (0.5 to 2.5 cm), moderate (2.5 to 7.0 cm) and, severe (> 7 cm). Pain at injection site was graded as mild (hurt if gently touched (example, whimpers, winces, protests, or withdraws), moderate (hurt if gently touched [with crying]), and severe (caused limitation of limb movement). Participants may be represented in more than 1 row. Here, "Any" for redness, swelling and pain at injection site represents any grade of these local reactions among mild, moderate or severe.
4. Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2 [ Time Frame: Within 7 days after Vaccination 2 ]
   Systemic events included fever, decreased appetite, drowsiness(increased sleep) and irritability, were recorded daily using an electronic diary. Fever graded as:1) < 38.0 degrees C, 2) >= 38.0 degree C to 38.4 degree C, 3)38.5 degree C to 38.9 degree C, 4) 39.0 degree C to 40.0 degree C, 5) >40.0 degree C. Decreased appetite graded as: mild(decreased interest in eating), moderate(decreased oral intake), and severe(refusal to feed). Drowsiness graded as: mild (increased or prolonged sleeping bouts), moderate (slightly subdued; interfering with daily activity), and severe (disabling; not interested in usual daily activity). Irritability graded as: mild (easily consolable), moderate (required increased attention), and severe (inconsolable; crying could not be comforted). Participants may be represented in >1 row. Here, "Any" for decreased appetite, drowsiness, irritability represents any grade of these systemic reactions among mild, moderate or severe.
5. Percentage of Participants With Local Reactions Within 7 Days After Vaccination 3 [ Time Frame: Within 7 days after Vaccination 3 ]
   Local reactions were recorded daily using an electronic diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild (0.5 to 2.5 cm), moderate (2.5 to 7.0 cm) and, severe (> 7 cm). Pain at injection site was graded as mild (hurt if gently touched (example, whimpers, winces, protests, or withdraws), moderate (hurt if gently touched [with crying]), and severe (caused limitation of limb movement). Participants may be represented in more than 1 row. Here, "Any" for redness, swelling and pain at injection site represents any grade of these local reactions among mild, moderate or severe.
6. Percentage of Participants With Systemic Events Within 7 Days After Vaccination 3 [ Time Frame: Within 7 days after Vaccination 3 ]
   Systemic events included fever, decreased appetite, drowsiness(increased sleep) and irritability, were recorded daily using an electronic diary. Fever graded as:1) < 38.0 degrees C, 2) >= 38.0 degree C to 38.4 degree C, 3)38.5 degree C to 38.9 degree C, 4) 39.0 degree C to 40.0 degree C, 5) >40.0 degree C. Decreased appetite graded as: mild(decreased interest in eating), moderate(decreased oral intake), and severe(refusal to feed). Drowsiness graded as: mild (increased or prolonged sleeping bouts), moderate (slightly subdued; interfering with daily activity), and severe (disabling; not interested in usual daily activity). Irritability graded as: mild (easily consolable), moderate (required increased attention), and severe (inconsolable; crying could not be comforted). Participants may be represented in >1 row. Here, "Any" for decreased appetite, drowsiness, irritability represents any grade of these systemic reactions among mild, moderate or severe.
7. Percentage of Participants With Local Reactions Within 7 Days After Vaccination 4 [ Time Frame: Within 7 days after Vaccination 4 ]
   Local reactions were recorded daily using an electronic diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild (0.5 to 2.5 cm), moderate (2.5 to 7.0 cm) and, severe (> 7 cm). Pain at injection site was graded as mild (hurt if gently touched (example, whimpers, winces, protests, or withdraws), moderate (hurt if gently touched [with crying]), and severe (caused limitation of limb movement). Participants may be represented in more than 1 row. Here, "Any" for redness, swelling and pain at injection site represents any grade of these local reactions among mild, moderate or severe.
8. Percentage of Participants With Systemic Events Within 7 Days After Vaccination 4 [ Time Frame: Within 7 days after Vaccination 4 ]
   Systemic events included fever, decreased appetite, drowsiness(increased sleep) and irritability, were recorded daily using an electronic diary. Fever graded as:1) < 38.0 degrees C, 2) >= 38.0 degree C to 38.4 degree C, 3)38.5 degree C to 38.9 degree C, 4) 39.0 degree C to 40.0 degree C, 5) >40.0 degree C. Decreased appetite graded as: mild(decreased interest in eating), moderate(decreased oral intake), and severe(refusal to feed). Drowsiness graded as: mild (increased or prolonged sleeping bouts), moderate (slightly subdued; interfering with daily activity), and severe (disabling; not interested in usual daily activity). Irritability graded as: mild (easily consolable), moderate (required increased attention), and severe (inconsolable; crying could not be comforted). Participants may be represented in >1 row. Here, "Any" for decreased appetite, drowsiness, irritability represents any grade of these systemic reactions among mild, moderate or severe.
9. Percentage of Participants With Adverse Events (AEs) After Vaccination 1 up to 1 Month After Vaccination 3 [ Time Frame: From Vaccination 1 up to 1 Month after Vaccination 3 (for a maximum study duration of 3 months) ]
   An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship.
10. Percentage of Participants With Adverse Events (AEs) From Vaccination 4 up to 1 Month After Vaccination 4 [ Time Frame: From Vaccination 4 up to 1 month after Vaccination 4 (for a maximum study duration of 1 month) ]
    An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship.
11. Percentage of Participants With Serious Adverse Events (SAEs) After Vaccination 1 up to 1 Month After Vaccination 4 [ Time Frame: From Vaccination 1 up to 1 month after Vaccination 4 (for a maximum study duration of 11.5 months) ]
    An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
12. Number of Participants With New Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Vaccination 3 up to Vaccination 4 [ Time Frame: From 1 month after Vaccination 3 up to Vaccination 4 (for a maximum study duration of 7.5 months) ]
    A newly diagnosed chronic medical condition was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects.

Secondary Outcome Measures :

1. Percentage of Participants With Immunoglobulin G (IgG) Concentrations Greater Than or Equal to (>=) Pre-defined Thresholds for Each of the Pneumococcal Serotypes Measured 1 Month After Vaccination 3 [ Time Frame: 1 month after Vaccination 3 ]
   Percentage of participants achieving predefined antibody threshold: >=0.35 microgram per milliliter (mcg/mL) for the 10 pneumococcal serotypes 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19F and 23F; threshold >= 0.23 mcg/mL for serotype 5, threshold >= 0.10 mcg/mL for serotype 6B, threshold >= 0.12 mcg/mL for serotype 19A, along with the corresponding 95 percent (%) confidence interval (CI) are reported.
2. Percentage of Participants With Immunoglobulin G (IgG) Concentrations Greater Than or Equal to (>=) Pre-defined Thresholds for Each of the Pneumococcal Serotypes Measured 1 Month After Vaccination 4 [ Time Frame: 1 month after Vaccination 4 ]
   Percentage of participants achieving predefined antibody threshold >=0.35 mcg/mL for the 10 pneumococcal serotypes 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19F and 23F, threshold >= 0.23 mcg/mL for serotype 5, threshold >= 0.10 mcg/mL for serotype 6B, threshold >= 0.12 mcg/mL for serotype 19A, along with the corresponding 95% CI are reported.
3. Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for Each of Pneumococcal Serotypes Measured 1 Month After Vaccination 3 [ Time Frame: 1 month after Vaccination 3 ]
   Antibody (IgG) GMCs for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) and corresponding 2-sided 95% CI are reported.
4. Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for Each of Pneumococcal Serotypes Measured 1 Month After Vaccination 4 [ Time Frame: 1 month after Vaccination 4 ]
   Antibody (IgG) GMCs for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) and corresponding 2-sided 95% CI are reported.
5. Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for Each of Pneumococcal Serotypes Measured 1 Month After Vaccination 3 [ Time Frame: 1 month after Vaccination 3 ]
   Antibody-mediated serum OPA against the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) was measured centrally using a pneumococcal OPA assay. Initial results were measured as OPA titers, which were then logarithmically transformed for analysis; geometric means calculated and expressed as GMTs.
6. Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) for Each of Pneumococcal Serotypes Measured 1 Month After Vaccination 4 [ Time Frame: 1 month after Vaccination 4 ]
   Antibody-mediated serum OPA against the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) was measured centrally using a pneumococcal OPA assay. Initial results were measured as OPA titers, which were then logarithmically transformed for analysis; geometric means calculated and expressed as GMTs.
7. Percentage of Participants With Opsonophagocytic Activity (OPA) Titers >= Lower Limit of Quantitation (LLOQ) for Each of Pneumococcal Serotypes Measured 1 Month After Vaccination 3 [ Time Frame: 1 month after Vaccination 3 ]
   Percentage of participants achieving OPA titer >=LLOQ along with 95% CI for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) determined in blood samples of participants was presented. LLOQ (measured in mcg/mL) for each serotype is as follows: Serotype 1=18; Serotype 3=12; Serotype 4=21; Serotype 5=29; Serotype 6A=37; Serotype 6B=43; Serotype 7F=113; Serotype 9V=141; Serotype 14=35; Serotype 18C=31; Serotype 19A=18; Serotype 19F=48; Serotype 23F=13.
8. Percentage of Participants With Opsonophagocytic Activity (OPA) Titers >= Lower Limit of Quantitation (LLOQ) for Each of Pneumococcal Serotypes Measured 1 Month After Vaccination 4 [ Time Frame: 1 month after Vaccination 4 ]
   Percentage of participants achieving OPA titer >=LLOQ along with 95% CI for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) determined in blood samples of participants was presented. LLOQ (measured in mcg/mL) for each serotype is as follows: Serotype 1=18; Serotype 3=12; Serotype 4=21; Serotype 5=29; Serotype 6A=37; Serotype 6B=43; Serotype 7F=113; Serotype 9V=141; Serotype 14=35; Serotype 18C=31; Serotype 19A=18; Serotype 19F=48; Serotype 23F=13.

Eligibility Criteria

• Ages Eligible for Study: 42 Days to 72 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Evidence of a personally signed and dated informed consent document indicating that the parent(s)/legal guardian(s) has/have been informed of all pertinent aspects of the study.
2. Parent(s)/legal guardian(s)/caregiver(s) willing and able to comply with scheduled visits, treatment plan, and other study procedures.
3. Aged 6 weeks (42 to 72 days) at the time of vaccination. (The day of birth is considered Day 0.)
4. Available for the entire study period and whose parent(s)/legal guardian(s)/caregiver(s) can be reached by telephone.
5. Healthy infant as determined by medical history, physical examination, and judgment of the investigator.
6. Weight of 3.0 kg or greater at the time of vaccination.

Exclusion Criteria:

1. Infant who is a direct descendant (child, grandchild) of

   • Investigator site staff members directly involved in the conduct of the study, or
   • Site staff members otherwise supervised by the investigator, or
   • Pfizer employees directly involved in the conduct of the study.
2. Participation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study participation. Participation in purely observational studies is acceptable.
3. Previous vaccination with licensed or investigational pneumococcal conjugate vaccine.
4. A previous anaphylactic reaction to any vaccine or vaccine-related component.
5. Contraindication to vaccination with pneumococcal conjugate vaccine, or any other vaccine or vaccine component. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.
6. Known or suspected immune deficiency or suppression, including known human immunodeficiency virus infection.
7. Major known congenital malformation or serious chronic disorder.
8. Significant neurological disorder or history of seizure including febrile seizure, or significant stable or evolving disorders such as cerebral palsy, encephalopathy, hydrocephalus, or other significant disorders. Does not include resolving syndromes due to birth trauma such as Erb's palsy.
9. Other acute or chronic medical condition including recent laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
10. Receipt of blood products or gamma globulin (including hepatitis B immunoglobulin and monoclonal antibodies, eg, Synagis).

Contacts and Locations

Locations

India

B. J. Medical College & Civil Hospital

Ahmedabad, Gujarat, India, 380016

Manipal Hospital

Bengaluru, Karnataka, India, 560017

KEM Hospital Research Centre

Pune, Maharashtra, India, 411 011

Bharati Vidyapeeth University Medical College

Pune, Maharashtra, India, 411043

Sri Ramachandra Hospital

Chennai, Tamil NADU, India, 600116

Kanchi Kamakoti Childs Trust Hospital

Chennai, Tamil Nadu, India, 600034

Sir Ganga Ram Hospital

New Delhi, India, 110060

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] February 14, 2017

Statistical Analysis Plan  [PDF] July 2, 2017

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lalwani SK, Ramanan PV, Sapru A, Sundaram B, Shah BH, Kaul D, Karthik Nagesh N, Kalina WV, Chand R, Ding M, Suroju S, Scott DA, Lockhart SP. Safety and immunogenicity of a multidose vial formulation of 13-valent pneumococcal conjugate vaccine administered with routine pediatric vaccines in healthy infants in India: A phase 4, randomized, open-label study. Vaccine. 2021 Nov 5;39(46):6787-6795. doi: 10.1016/j.vaccine.2021.09.029. Epub 2021 Oct 14.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03548337
• Other Study ID Numbers: B4671004; INDIA INFANT MDV ( Other Identifier: Alias Study Number ); 2016-005134-29 ( EudraCT Number )
• First Posted: June 7, 2018
• Results First Posted: September 30, 2020
• Last Update Posted: September 30, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No