Safety Study of 2 Formulations of GSK's Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants Starting at Age 6-12 Weeks

NCT03954743 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2082362018-001986-18
• Study Type: interventional
• Target: 1,351
• Locations: 5 countries
• Sites: 37

Brief Summary

The purpose of this study is to complete the total safety database size for GlaxoSmithKline Biologicals' (GSK's) human rotavirus (HRV) vaccine across the Porcine circovirus (PCV)-free development plan. This study used a purposely selected lot for PCV-free liquid HRV vaccine that is in the upper range of the usual release potencies. The PCV-free liquid HRV vaccine lots used were stored frozen in order to keep the titer stable until administration during the study. As the liquid formulation of GSK's HRV vaccine is not licensed in the US, the lyophilized formulation of the vaccine was used as a control in all phase III studies as part of the PCV-free development plan.

Conditions

Infections, Rotavirus

Keywords

HRV; Lyophilized formulation; Liquid formulation; Human rotavirus vaccine; Rotarix; Healthy infants; PCV-free; Porcine circovirus-free

Outcome Measures

Primary Outcomes (4)

• Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination

  Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of AE regardless of intensity grade or relation to study vaccination.

  During the 8-day follow-up period after the first vaccination (vaccines administered at Day 1)

• Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination

  Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of AE regardless of intensity grade or relation to study vaccination.

  During the 8-day follow-up period after the second vaccination (vaccines administered at Month 1 or Month 2)

• Number of Subjects With Any Unsolicited AEs

  An unsolicited AE is defined as any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment, and reported in addition to those solicited during the clinical study and any 'solicited' AE with onset outside the specified period of follow-up for solicited symptoms. Any = occurrence of AE regardless of intensity grade or relation to study vaccination.

  During the 31-day follow-up period across doses (vaccines administered at Day 1 and at Month 1 or Month 2)

• Number of Subjects With Any Serious Adverse Events (SAEs)

  An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any = occurrence of SAE regardless of intensity grade or relation to study vaccination.

  Throughout the study period (from Day 1 up to Month 7 or Month 8)

Study Arms (2)

HRV PCV-free Liq Group

EXPERIMENTAL

Subjects aged 6 to 12 weeks at the time of first vaccination, who received two doses of oral live-attenuated human rotavirus (HRV) porcine circovirus (PCV)-free vaccine in liquid formulation, one at Day 1 and one at Month 1 or Month 2, according to the immunization schedule for rotavirus (RV) vaccine administration in participating countries. PCV-free implies no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used.

Biological: PCV-free liquid formulation of GSK's oral live attenuated HRV vaccine

HRV Lyo group

ACTIVE COMPARATOR

Subjects aged 6 to 12 weeks at the time of first vaccination, who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in lyophilized formulation, one at Day 1 and one at Month 1 or Month 2, according to the immunization schedule for rotavirus (RV) vaccine administration in participating countries.

Biological: Lyophilized formulation of GSK's oral live attenuated HRV vaccine

Interventions

PCV-free liquid formulation of GSK's oral live attenuated HRV vaccine BIOLOGICAL

2 doses administered orally at Day 1 and at Month 1 or Month 2, according to the immunization schedule for RV vaccine administration in participating countries.

HRV PCV-free Liq Group

Lyophilized formulation of GSK's oral live attenuated HRV vaccine BIOLOGICAL

2 doses administered orally at Day 1 and at Month 1 or Month 2, according to the immunization schedule for RV vaccine administration in participating countries.

HRV Lyo group

Eligibility Criteria

• Age: 6 Weeks - 12 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• All subjects must satisfy all the following criteria at study entry:
• Subjects' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
• Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.

You may not qualify if:

• Medical conditions
• Uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for Intussusception (IS).
• Very prematurely born infants (born ≤28 weeks of gestation).
• History of IS.
• Family history of congenital or hereditary immunodeficiency.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Hypersensitivity to latex.
• Major congenital defects or serious chronic illness, as assessed by the investigator.
• Previous confirmed occurrence of Rotavirus Gastroenteritis (RV GE).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
• History of Severe combined immunodeficiency (SCID). Prior/Concomitant therapy
• Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 1), or planned use during the study period.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study, and other licensed routine childhood vaccinations.
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Administration of immunoglobulins and/or any blood products from birth or planned administration during the study period.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (37)

GSK Investigational Site

Birmingham, Alabama, 35235, United States

Location

GSK Investigational Site

Colorado Springs, Colorado, 80922, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40291, United States

Location

GSK Investigational Site

Frederick, Maryland, 21702, United States

Location

GSK Investigational Site

Fall River, Massachusetts, 02721-1735, United States

Location

GSK Investigational Site

Bingham Farms, Michigan, 48025, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68504, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68516, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68522, United States

Location

GSK Investigational Site

East Orange, New Jersey, 07108, United States

Location

GSK Investigational Site

Syracuse, New York, 13210, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45245, United States

Location

GSK Investigational Site

Fairfield, Ohio, 45014, United States

Location

GSK Investigational Site

Corvallis, Oregon, 97330, United States

Location

GSK Investigational Site

Draper, Utah, 84020, United States

Location

GSK Investigational Site

Murray, Utah, 84107, United States

Location

GSK Investigational Site

Orem, Utah, 84057, United States

Location

GSK Investigational Site

South Jordan, Utah, 84095, United States

Location

GSK Investigational Site

Charlottesville, Virginia, 22902, United States

Location

GSK Investigational Site

Calgary, Alberta, T3B 6A8, Canada

Location

GSK Investigational Site

Surrey, British Columbia, V3S 2N6, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

Location

GSK Investigational Site

Brampton, Ontario, L6T 0G1, Canada

Location

GSK Investigational Site

London, Ontario, N5W 6A2, Canada

Location

GSK Investigational Site

Sarnia, Ontario, N7T 4X3, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3T 1C5, Canada

Location

GSK Investigational Site

Québec, G1V 4G2, Canada

Location

GSK Investigational Site

Pokfulam, Hong Kong

Location

GSK Investigational Site

Shatin, Hong Kong

Location

GSK Investigational Site

Changhua, 500, Taiwan

Location

GSK Investigational Site

Kaohsiung City, 83301, Taiwan

Location

GSK Investigational Site

Taipei, 100, Taiwan

Location

GSK Investigational Site

Taipei, 104, Taiwan

Location

GSK Investigational Site

Eskişehir, 26040, Turkey (Türkiye)

Location

GSK Investigational Site

Izmir, 35340, Turkey (Türkiye)

Location

GSK Investigational Site

Kayseri, 38030, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Rotavirus Infections

Condition Hierarchy (Ancestors)

Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Data were collected in an observer-blind manner. By observer-blind, it is meant that during the study period, the vaccine(s) recipient and those responsible for the evaluation of any study endpoint (e.g. safety and reactogenicity) were all unaware of which vaccine was administered.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 17, 2019
• Study Start: July 19, 2019
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2020
• Last Updated: March 10, 2022
• Results First Posted: June 18, 2021

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• 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

TW (4); TU (3); CA (9); HK (2); US (19)