Evaluation of Immunogenicity and Safety of Two Formulations of GSK Biologicals' Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants Starting at Age 6-12 Weeks

NCT02914184 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 1154612016-000598-19
• Study Type: interventional
• Target: 1,612
• Locations: 8 countries
• Sites: 66

Brief Summary

The purpose of this study is to evaluate the clinical consistency of three production lots of the Porcine circovirus (PCV)-free liquid formulation of oral live attenuated human rotavirus (HRV) vaccine and to evaluate the PCV-free liquid formulation of HRV vaccine as compared to the currently licensed lyophilised formulation of the HRV vaccine in terms of immunogenicity, reactogenicity and safety when administered as a two-dose vaccination in healthy infants starting at age 6-12 weeks. No new subjects will be enrolled in the extension phase of the study.

Conditions

Infections, Rotavirus; Rotavirus Vaccines

Keywords

Safety; Healthy infants; Immunogenicity; Human Rotavirus (HRV)

Outcome Measures

Primary Outcomes (5)

• Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C)

  Antibody concentrations against Rota Virus (RV) were determined as Geometric Mean Antibody Concentration (GMC) and expressed as Units per milliliter (U/mL).

  At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)

• Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to Cut-off Value in Porcine Circovirus (PCV) -Free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Control Group

  Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (\<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). For this outcome measure, the three groups (Liq\_A, Liq\_B \& Liq\_C) were pooled into a single group (Liq\_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq\_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo\_Control group) in terms of seroconversion rates of 1-2 months after Dose 2.

  At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)

• Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group

  Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (\<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). The analysis was assessed to demonstrate the immunogenicity of PCV-free liquid HRV vaccine as compared to the currently licensed lyophilised HRV vaccine (individual HRV liquid groups) in terms of seroconversion rates 1-2 months after Dose 2.

  At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)

• Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Lyophilised Control Group

  Antibody concentrations against RV were determined as GMCs and expressed as U/mL. For this outcome measure, the three groups (Liq\_A, Liq\_B \& Liq\_C) were pooled into a single group (Liq\_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq\_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo\_Control group) in terms of antibody concentrations at 1-2 months after Dose 2.

  At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)

• Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group

  Antibody concentrations against RV were determined as GMCs and expressed as U/mL. The analysis was assessed to demonstrate the immunogenicity of the PCV-free liquid HRV vaccine (individual HRV liquid groups) to that of the currently licensed lyophilised HRV vaccine in terms of serum anti-RV IgA antibody concentrations 1-2 months after Dose 2.

  At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)

Secondary Outcomes (5)

• Percentage of Subjects With Anti-RV IgA Concentrations (Pooled HRV Liquid Group)

  At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)

• Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups)

  At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)

• Number of Subjects With Any Solicited General Adverse Events (AEs).

  During the 8 days (Day 1 to Day 8) follow-up period after each dose of HRV vaccine

• Number of Subjects With Any Unsolicited AEs.

  During the 31 day (Day 1 to Day 31) follow-up period after HRV vaccination across doses

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

  During the entire study period (Day 1 to Month 7-8)

Study Arms (4)

Liq_A Group

EXPERIMENTAL

All subjects will receive two doses of PCV-free HRV liquid formulation lot A, at 6 and 12 weeks of age

Biological: HRV PCV-free liquid vaccine

Liq_B Group

EXPERIMENTAL

All subjects will receive two doses of PCV-free HRV liquid formulation lot B, at 6 and 12 weeks of age

Biological: HRV PCV-free liquid vaccine

Liq_C Group

EXPERIMENTAL

All subjects will receive two doses of PCV-free HRV liquid formulation lot C, at 6 and 12 weeks of age

Biological: HRV PCV-free liquid vaccine

Lyo Group

ACTIVE COMPARATOR

All subjects will receive two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age

Biological: Rotarix

Interventions

HRV PCV-free liquid vaccine BIOLOGICAL

Subjects will receive two doses of PCV-free HRV vaccine at 6 and 12 weeks of age. The vaccine will be administered orally

Liq_A Group; Liq_B Group; Liq_C Group

Rotarix BIOLOGICAL

Subjects will receive two doses of currently licensed lyophilised HRV vaccine at 6 and 12 weeks of age. The vaccine will be administered orally

Lyo Group

Eligibility Criteria

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

You may qualify if:

• Subjects' parent(s)/LAR(s) who, in the opinion of the investigator can and will comply with the requirements of the protocol.
• Written informed consent obtained from the parent(s)/LAR(s) (Legally acceptable representatives) of the subject prior to performing any study specific procedure.
• A male or female infant between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination.
• Born full-term (i.e., between a gestation period of 37 weeks 0 days and 41 weeks 6 days).
• Healthy subjects as established by medical history and clinical examination before entering into the study.

You may not qualify if:

• Child in care
• Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day-29 to Day 0), or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone (0.5 mg/kg/day, or equivalent). Inhaled and topical steroids are allowed.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
• Administration of long-acting immune-modifying drugs at any time 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 of vaccine administration and ending at Visit 3, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study and other licensed routine childhood vaccinations.
• 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.
• Uncorrected congenital malformation of the gastrointestinal tract that would predispose for Intussusception (IS).
• 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.
• Major congenital defects or serious chronic illness.
• Previous vaccination against RV.
• Previous confirmed occurrence of RVGE.
• GE within 7 days preceding the study vaccine administration.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (66)

GSK Investigational Site

Birmingham, Alabama, 35235, United States

Location

GSK Investigational Site

Anaheim, California, 92804, United States

Location

GSK Investigational Site

Paramount, California, 90723, United States

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GSK Investigational Site

Sacramento, California, 95815, United States

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GSK Investigational Site

San Jose, California, 95119, United States

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GSK Investigational Site

Nampa, Idaho, 83686, United States

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GSK Investigational Site

Newton, Kansas, 67114, United States

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GSK Investigational Site

Topeka, Kansas, 66604, United States

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GSK Investigational Site

Kansas City, Missouri, 64108, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44121, United States

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GSK Investigational Site

Erie, Pennsylvania, 16506, United States

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GSK Investigational Site

Cheraw, South Carolina, 29520, United States

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GSK Investigational Site

North Charleston, South Carolina, 29456-9170, United States

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GSK Investigational Site

Layton, Utah, 84041, United States

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GSK Investigational Site

Murray, Utah, 84107, United States

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GSK Investigational Site

Orem, Utah, 84057, United States

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GSK Investigational Site

Provo, Utah, 84604, United States

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GSK Investigational Site

Syracuse, Utah, 84075, United States

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GSK Investigational Site

Marshfield, Wisconsin, 54449, United States

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GSK Investigational Site

San José, Provincia de San José, Costa Rica

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GSK Investigational Site

San José, Costa Rica

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GSK Investigational Site

Espoo, 02230, Finland

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GSK Investigational Site

Helsinki, 00100, Finland

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GSK Investigational Site

Helsinki, 00930, Finland

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GSK Investigational Site

Jarvenpaa, 04400, Finland

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GSK Investigational Site

Kokkola, 67100, Finland

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GSK Investigational Site

Oulu, 90220, Finland

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GSK Investigational Site

Pori, 28100, Finland

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GSK Investigational Site

Seinäjoki, 60100, Finland

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GSK Investigational Site

Tampere, 33100, Finland

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GSK Investigational Site

Turku, 20520, Finland

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GSK Investigational Site

Mannheim, Baden-Wurttemberg, 68161, Germany

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GSK Investigational Site

Tauberbischofsheim, Baden-Wurttemberg, 97941, Germany

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GSK Investigational Site

Schönau am Königssee, Bavaria, 83471, Germany

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GSK Investigational Site

Goch, North Rhine-Westphalia, 47574, Germany

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GSK Investigational Site

Frankenthal, Rhineland-Palatinate, 67227, Germany

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GSK Investigational Site

Bramsche, 49565, Germany

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GSK Investigational Site

Chiba, 274-0063, Japan

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GSK Investigational Site

Chiba, 299-4503, Japan

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GSK Investigational Site

Saitama, 350-0001, Japan

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GSK Investigational Site

Saitama, 360-0846, Japan

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GSK Investigational Site

Tokyo, 146-0095, Japan

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GSK Investigational Site

Tokyo, 167-0052, Japan

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GSK Investigational Site

Tokyo, 190-0002, Japan

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GSK Investigational Site

Gangwon-do, 26426, South Korea

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GSK Investigational Site

Gyeonggido, 442723, South Korea

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GSK Investigational Site

Incheon, 21431, South Korea

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GSK Investigational Site

Seoul, 01450, South Korea

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GSK Investigational Site

Seoul, 02447, South Korea

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GSK Investigational Site

Seoul, 04619, South Korea

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GSK Investigational Site

Málaga, Andalusia, 29004, Spain

Location

GSK Investigational Site

Antequera/Málaga, 29200, Spain

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GSK Investigational Site

Castellon, 12004, Spain

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GSK Investigational Site

Castellon, 12530, Spain

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GSK Investigational Site

Madrid, 28050, Spain

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GSK Investigational Site

Marbella, 29600, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Valencia, 46020, Spain

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GSK Investigational Site

Valencia, 46023, Spain

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GSK Investigational Site

Valencia, 46200, Spain

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GSK Investigational Site

Hsinchu, 300, Taiwan

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GSK Investigational Site

Taichung, 404, Taiwan

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GSK Investigational Site

Taichung, 407, Taiwan

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GSK Investigational Site

Taipei, 100, Taiwan

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GSK Investigational Site

Taipei, 104, Taiwan

Location

GSK Investigational Site

Taoyuan District, 333, Taiwan

Location

Related Publications (1)

• Salamanca de la Cueva I, Pahud B, Huang LM, Leonardi M, Garcia-Sicilia J, Cespedes J, Abdelnour A, Tamura T, Kuroki H, Chiu NC, Virta M, Kokko S, Horn M, Panzer F, Kim JH, Jin L, Moerman L, Debacq C, Parra J, Ugarte A, Bi D; Rota-081 Study Group. Immunogenicity and safety of porcine circovirus-free human rotavirus vaccine in healthy infants: a phase III, randomized trial. J Infect Dis. 2020 May 4;225(12):2106-15. doi: 10.1093/infdis/jiaa210. Online ahead of print.

  PMID: 32365189 BACKGROUND

MeSH Terms

Conditions

Rotavirus Infections

Interventions

RIX4414 vaccine

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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: September 26, 2016
• Study Start: October 27, 2016
• Primary Completion: June 27, 2018
• Study Completion: November 26, 2018
• Last Updated: July 21, 2020
• Results First Posted: October 14, 2019

Record last verified: 2020-07

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

US (19); TW (6); ES (10); DE (6); FI (10); CO (2); KR (6); JP (7)