A Study to Compare the Immunogenicity of GSK Biologicals' 10Pn-PD-DiT 4-dose Presentation to the Licensed 1-dose Synflorix™ (10Pn-PD-DiT) Vaccine When Co-administered With DTPw-combination Vaccine in Healthy Infants

NCT02447432 | Completed Phase 3 Results DMC

• 1 other identifier: 200799
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of the study is to demonstrate that an investigational 4-dose presentation of the 10Pn-PD-DiT vaccine with preservative is non-inferior to the licensed presentation of Synflorix (preservative-free) in terms of immune responses to the 10 vaccine pneumococcal serotypes (primary objective) and to the vaccine-related pneumococcal serotype 19A (first secondary objective), after administration of a 3-dose primary vaccination course at 6, 10 and 18 weeks of age co-administered with the first 2 doses of DTPw-HBV/Hib vaccine given at 6, 10 and 14 weeks of age (according to the Expanded Program on Immunization (EPI) schedule). In addition, the study will also assess the safety, reactogenicity, immunogenicity and antibody persistence (approximately 7 months following primary vaccination) of the 4-dose presentation of the 10Pn-PD-DiT vaccine given as primary vaccination schedule at 6, 10 and 18 weeks of age followed by a booster dose at 38 weeks. This study also aims at assessing the safety, reactogenicity and immunogenicity of the 4-dose presentation of the 10Pn-PD-DiT vaccine when given as a booster dose at approximately 9 months of age.

Conditions

Infections, Streptococcal

Keywords

Invasive disease by Streptococcus pneumoniae (S. pneumoniae) (including sepsis, meningitis, pneumonia, bacteraemia and acute otitis media); Infants; Multidose; Haemophilus influenzae; Streptococcus pneumoniae; Preservative; Safety; Pneumonia; Immunogenicity; Pneumococcal conjugate vaccine; Acute otitis media caused by non-typeable Haemophilus influenzae (NTHi).; Respiratory tract infections

Outcome Measures

Primary Outcomes (1)

• Antibody Concentrations Against Pneumococcal Serotypes (Epoch 001)

  Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. Primary outcome results correspond to antibody concentrations for the 10 vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

  At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine

Secondary Outcomes (13)

• Antibody Concentrations Against Pneumococcal Serotypes (Epoch 002)

  At Month 8 and Month 9, e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine

• Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes (Epoch 001)

  At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine

• Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes (Epoch 002)

  At study Month 8 and Month 9, e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine

• Concentrations of Antibodies Against Protein D (Anti-PD) (Epoch 001)

  At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine

• Concentrations of Antibodies Against Protein D (Anti-PD) (Epoch 002)

  At study Month 9, e.g.: at one month post booster vaccination with pneumococcal vaccine

Study Arms (2)

10Pn_4d Group

EXPERIMENTAL

Subjects received 10Pn-PD-DIT, in its investigational 4-dose presentation (4 doses in total with each single dose injected at Study Months 0, 1, 3 and 8), co administered with DTPw-HBV/Hib vaccine (3 doses injected at Study Months 0, 1 and 2).

Biological: Pneumococcal vaccine GSK1024850A (10Pn-PD-DiT) vaccine (4-dose presentation); Biological: DTPw-HBV/Hib

10Pn Group

ACTIVE COMPARATOR

Subjects received 10Pn-PD-DIT, in its licensed 1-dose presentation (4 doses in total with each single dose injected at Study Months 0, 1, 3 and 8), co administered with DTPw-HBV/Hib vaccine (3 doses injected at Study Months 0, 1 and 2).

Biological: Pneumococcal vaccine GSK1024850A (10Pn-PD-DiT) vaccine (1-dose presentation); Biological: DTPw-HBV/Hib

Interventions

Pneumococcal vaccine GSK1024850A (10Pn-PD-DiT) vaccine (4-dose presentation) BIOLOGICAL

4 doses by intramuscular injection in the right left anterolateral thigh

Also known as: 10Pn, 10PN-PD-DiT, GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate GSK1024850A (10Pn-PD-DiT)

10Pn_4d Group

Pneumococcal vaccine GSK1024850A (10Pn-PD-DiT) vaccine (1-dose presentation) BIOLOGICAL

4 doses by intramuscular injection in the right anterolateral thigh

Also known as: Synflorix™, GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate GSK1024850A (10Pn-PD-DiT) vaccine

10Pn Group

DTPw-HBV/Hib BIOLOGICAL

3 doses by intramuscular injection in the left anterolateral thigh

Also known as: GSK Biologicals' diphtheria-tetanus-whole cell pertussis-hepatitis B and Haemophilus influenzae type b vaccine

10Pn Group; 10Pn_4d Group

Eligibility Criteria

• Age: 42 Days - 76 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Subjects for whom, in the opinion of the investigator, the parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] can and will comply with the requirements of the protocol (e.g., return for vaccination and follow-up visits).
• A male or female between, and including 6-10 weeks (42-76 days) of age at the time of the first vaccination.
• Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the subject. For all subjects, the consent form should be countersigned by a witness.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Born full-term (i.e., after a gestation period from 37 to 42 weeks).

You may not qualify if:

• Child in care.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. Inhaled and topical steroids are allowed.
• Planned administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab).
• Administration or planned administration of a vaccine not foreseen by the study protocol administered during the period starting from 30 days before each dose of study vaccines and ending 30 days after with the following exceptions:
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product
• Previous vaccination against diphtheria, tetanus, pertussis, H. influenzae type b and/or S. pneumoniae.
• History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, and H. influenzae type b disease.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Family history of congenital or hereditary immunodeficiency.
• Major congenital defects or serious chronic illness.
• History of any neurological disorders or seizures.
• Acute disease and/or fever at the time of enrolment.
• Fever is defined as temperature ≥ 37.5°C for oral, axillary or tympanic route, or ≥ 38.0°C on rectal route. The preferred route for recording temperature in this study will be axillary.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Dhaka, 1000, Bangladesh

Location

Related Publications (1)

• Zaman K, Zaman SF, Zaman F, Aziz A, Faisal SB, Traskine M, Habib MA, Ruiz-Guinazu J, Borys D. Immunologic non-inferiority and safety of the investigational pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) 4-dose vial presentation compared to the licensed PHiD-CV 1-dose vial presentation in infants: A phase III randomized study. Vaccine. 2018 Jan 29;36(5):698-706. doi: 10.1016/j.vaccine.2017.12.034. Epub 2017 Dec 23.

  PMID: 29277353 DERIVED

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.

MeSH Terms

Conditions

Streptococcal Infections; Meningitis; Pneumonia; Toxemia; Otitis Media; Haemophilus Infections; Respiratory Tract Infections

Interventions

Vaccines; PHiD-CV vaccine

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Neuroinflammatory Diseases; Nervous System Diseases; Lung Diseases; Respiratory Tract Diseases; Otitis; Ear Diseases; Otorhinolaryngologic Diseases; Pasteurellaceae Infections; Gram-Negative Bacterial Infections

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Limitations and Caveats

None reported.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: May 18, 2015
• Study Start: June 11, 2015
• Primary Completion: January 23, 2016
• Study Completion: May 22, 2016
• Last Updated: August 2, 2018
• Results First Posted: March 16, 2017

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BA (1)