A Study to Test if a Third Dose of the Vaccine is Safe in Current and Former Smokers Aged 40 to 80 Years Old and to Gather Information on the Immune Response Following the Third Dose of the Vaccine

NCT03443427 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2077592017-002941-31
• Study Type: interventional
• Target: 200
• Locations: 3 countries
• Sites: 8

Brief Summary

The purpose of this study is to test two different vaccine schedules to be used for administering the investigational NTHi Mcat vaccine that will be targeting patients with chronic obstructive pulmonary disease (COPD) to prevent acute exacerbations. An acute exacerbation is when the breathlessness in COPD patients will get even worse than it normally already is, sometimes to the point where oxygen therapy is required. In previous studies, study participants have received two doses of the vaccine according to a 0, 2 month vaccination schedule, in addition to standard care. The current study will find out if a third dose of the study vaccine against NTHi/Mcat is safe and working well. The study will also investigate if the third dose of vaccine works best when given after 6 months or after 12 months.

Conditions

Respiratory Disorders

Keywords

Non-typeable Haemophilus influenzae; Moraxella catarrhalis; Safety; Third vaccine dose; Vaccination; Immunogenicity

Outcome Measures

Primary Outcomes (5)

• Number of Subjects Reported With Each Solicited Local Adverse Event (AE) (Any and Grade 3) Within Each Vaccination Schedule

  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) injection site.

  During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered at Day 1, Day 61, Day 181 and Day 361

• Number of Subjects Reported With Each Solicited General Adverse Event (AE) (Any and Grade 3) Within Each Vaccination Schedule

  Assessed solicited general symptoms were chills, gastrointestinal symptoms (including nausea, vomiting, diarrhoea and/or abdominal pain), fatigue, myalgia, headache and fever \[defined Oral cavity or axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C.

  During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered at Day 1, Day 61, Day 181 and Day 361

• Number of Subjects Reported With Any Unsolicited Adverse Event (AE) Within Each Vaccination Schedule

  An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.

  During the 30-day follow-up period (the day of vaccination + 29 days) after each vaccination administered at Day 1, Day 61, Day 181 and Day 361

• Number of Subjects Reported With Any Serious Adverse Event (SAE) Within Each Vaccination Schedule

  An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject or was a congenital anomaly/birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician.

  From first vaccination (Day 1) up to Day 541 (an average of 18 months)

• Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs) Within Each Vaccination Schedule

  Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

  From first vaccination (Day 1) up to Day 541 (an average of 18 months)

Secondary Outcomes (11)

• Number of Subjects Reported With Any SAE Within Each Vaccination Schedule

  From Day 541 up to Day 721 (an average of 6 months)

• Number of Subjects Reported With Any pIMDs Within Each Vaccination Schedule

  From Day 541 up to Day 721 (an average of 6 months)

• Anti-Protein D (PD) Antibody Concentrations, as Measured by ELISA, Within Each Vaccination Schedule

  At Day 1, Day 91, Day 181, Day 211, Day 361, Day 391, Day 541 and Day 721

• Anti-Protein E (PE) Antibody Concentrations, as Measured by ELISA, Within Each Vaccination Schedule

  At Day 1, Day 91, Day 181, Day 211, Day 361, Day 391, Day 541 and Day 721

• Anti-Type IV Pili Subunit (PilA) Antibody Concentrations, as Measured by ELISA, Within Each Vaccination Schedule

  At Day 1, Day 91, Day 181, Day 211, Day 361, Day 391, Day 541 and Day 721

Study Arms (2)

Schedule 0-2-6 Group

EXPERIMENTAL

Subjects between, and including, 40 and 80 years of age at the time of the first vaccination, receiving three doses of the GSK3277511A investigational vaccine at Day 1 (Month 0), Day 61 (Month 2) and Day 181 (Month 6) and one dose of placebo at Day 361 (Month 12).

Biological: NTHi Mcat investigational vaccine (GSK3277511A); Biological: Placebo

Schedule 0-2-12 Group

EXPERIMENTAL

Subjects between, and including, 40 and 80 years of age at the time of the first vaccination, receiving three doses of the GSK3277511A investigational vaccine at Day 1 (Month 0), Day 61 (Month 2) and Day 361 (Month 12) and one dose of placebo at Day 181 (Month 6).

Biological: NTHi Mcat investigational vaccine (GSK3277511A); Biological: Placebo

Interventions

NTHi Mcat investigational vaccine (GSK3277511A) BIOLOGICAL

Two doses administered intramuscularly at Day 1 and Day 61 in the deltoid region of the non-dominant arm and a third dose administered at either Day 181 or Day 361, according to each vaccination scheduling defined per protocol.

Schedule 0-2-12 Group; Schedule 0-2-6 Group

Placebo BIOLOGICAL

One dose administered intramuscularly at either Day 181 or Day 361 in the deltoid region of the non-dominant arm.

Schedule 0-2-12 Group; Schedule 0-2-6 Group

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing any study specific procedure.
• A male or female between, and including, 40 and 80 years of age at the time of the first vaccination.
• Current or former smoker with a cigarette smoking history of ≥ 10 pack-years.
• Female subjects of non-childbearing potential may be enrolled in the study.
• Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
• Female subjects of childbearing potential may be enrolled in the study, if the subject:
• has practiced adequate contraception for 30 days prior to vaccination, and
• has a negative pregnancy test on the day of vaccination and
• has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

You may not qualify if:

• Use of any investigational or non-registered product (drug or vaccine) 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.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• 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 and ending 30 days after the last dose of vaccine administration, with the exception of any influenza or pneumococcal vaccine which may be administered ≥ 15 days preceding or following any study vaccine dose.
• 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 with any vaccine containing NTHi and/or Mcat antigens.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of or current autoimmune disease.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• Acute disease and/or fever at the time of enrolment.
• Fever is defined as temperature ≥37.5°C. The preferred location for measuring temperature in this study will be the oral cavity or the axilla.
• Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
• Pregnant or lactating female.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1J 2G2, Canada

Location

GSK Investigational Site

Würzburg, Bavaria, 97070, Germany

Location

GSK Investigational Site

Goch, North Rhine-Westphalia, 47574, Germany

Location

GSK Investigational Site

Chesterfield, Derbyshire, S40 4AA, United Kingdom

Location

GSK Investigational Site

Wellingborough, Northamptonshire, NN8 4RW, United Kingdom

Location

GSK Investigational Site

Axbridge, Somerset, BS26 2BJ, United Kingdom

Location

GSK Investigational Site

Chippenham, SN15 2SB, United Kingdom

Location

Related Publications (1)

• Galgani I, Annaratone M, Casula D, Di Maro G, Janssens M, Tasciotti A, Schwarz T, Ferguson M, Arora AK. Safety and immunogenicity of three doses of non-typeable Haemophilus influenzae-Moraxella catarrhalis (NTHi-Mcat) vaccine when administered according to two different schedules: a phase 2, randomised, observer-blind study. Respir Res. 2022 May 4;23(1):114. doi: 10.1186/s12931-022-02019-4.

  PMID: 35509077 DERIVED

MeSH Terms

Conditions

Respiration Disorders

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases

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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: By observer-blind, it is meant that during the course of the study, the vaccine recipient and those responsible for the evaluation of any study endpoint (e.g. safety, reactogenicity) will all be unaware of whether vaccine or placebo was administered. Each study site is responsible for having a blinding plan. To work in an observer-blind manner, vaccine preparation and administration will be done by authorised medical personnel (e.g. study nurse) who will not participate in any of the study clinical evaluation assays. Two teams of study personnel will hence be set up: * A team of unblinded personnel (responsible for the preparation and the administration of the vaccines) * A team of blinded personnel (responsible for the clinical evaluation of the subjects). The laboratory in charge of the laboratory testing will be blinded to the treatment, and codes will be used to link the subject and study (without any link to the treatment attributed to the subject) to each sample.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 23, 2018
• Study Start: March 20, 2018
• Primary Completion: December 31, 2019
• Study Completion: September 23, 2020
• Last Updated: August 31, 2021
• Results First Posted: November 12, 2020

Record last verified: 2021-07

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

DE (2); CA (2); GB (4)