Study to Assess the Immunogenicity and Safety of GSK's Investigational Vaccine (GSK3277511A) When Given to Healthy Smokers and Ex-smokers After Administration of Shingrix Vaccine

NCT ID: NCT03894969

Last Updated: 2024-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 541 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-23
• Study Completion Date: 2021-08-13

Brief Summary

This study will provide information regarding the sequential administration of two vaccines adjuvanted with AS01.

The aim of this study is to understand immunogenicity and safety of NTHi-Mcat vaccine when administered sequentially after Shingrix vaccine and to compare to the immunogenicity of NTHi-Mcat vaccine administered alone. This study will also provide information regarding whether a specific time period is required between the administration of these two different vaccines containing the same adjuvant- AS01 components.

The population of this study will include healthy smokers and ex-smokers of 50 to 80 years of age which will be used as a proxy for the COPD population.

Conditions

Respiratory Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Sh_NTHi-Mcat_1 Group

Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, and following a 1-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 91, and Day 151.

Group Type: EXPERIMENTAL

GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E

Intervention Type: BIOLOGICAL

2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm

Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)

Intervention Type: BIOLOGICAL

2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh\_NTHi-Mcat\_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm

Sh_NTHi-Mcat_3 Group

Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 3-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 151 and Day 211.

Group Type: EXPERIMENTAL

GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E

Intervention Type: BIOLOGICAL

2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm

Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)

Intervention Type: BIOLOGICAL

2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh\_NTHi-Mcat\_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm

Sh_NTHi-Mcat_6 Group

Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 6-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart at Day 241 and Day 301.

Group Type: EXPERIMENTAL

GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E

Intervention Type: BIOLOGICAL

2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm

Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)

Intervention Type: BIOLOGICAL

2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh\_NTHi-Mcat\_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm

NTHi-Mcat Group

Subjects enrolled in this group received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 1 and Day 61.

Group Type: ACTIVE_COMPARATOR

GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E

Intervention Type: BIOLOGICAL

2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm

Shingrix-Only Group

Subjects belonging to this group were originally randomized to either Sh\_NTHi-Mcat\_1 Group, Sh\_NTHi-Mcat\_3 Group or Sh\_NTHi-Mcat\_6 Group, they received at least 1, maximum 2 doses of GSK Biologicals Shingrix vaccine at Day 1 and Day 61, but didnt receive any dose of NTHI Mcat investigational vaccine. Only safety data were collected for these subjects.

Group Type: EXPERIMENTAL

Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)

Intervention Type: BIOLOGICAL

2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh\_NTHi-Mcat\_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm

Interventions

GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E

2 doses of the investigational NTHi-Mcat vaccine will be administered 2 months apart to all subjects in all the groups. The vaccine will be given intramuscularly (IM) in the upper deltoid of non-dominant arm

Intervention Type: BIOLOGICAL

Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)

2 doses of the Shingrix vaccine will be administered at days 1 and 61 to all subjects in groups Sh\_NTHi-Mcat\_1, 3 and 6. The vaccine will be given intramuscularly (IM) in the upper deltoid of the non-dominant arm

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Subjects 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 informed consent obtained from the subject prior to performance of any study specific procedure.
• A male or female between, and including, 50 years and 80 years of age at the time of the first vaccination.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Current or former smoker with a cigarette smoking history ≥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.

Exclusion Criteria

• Medical conditions
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of potential immune-mediated disease (pIMD). Note: If the subject has any condition on the list of pIMDs specified in the protocol, they must be excluded unless the aetiology is clearly documented to be non-immune mediated.

• Diagnosis of COPD regardless of severity.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Additionally, consider allergic reactions to other material or equipment related to study participation (such as materials that may possibly contain latex -gloves, syringes, etc).
• Has significant disease (including significant psychological disorders), in the opinion of the investigator, likely to interfere with the study and/or likely to cause death within the study duration.
• History of or current condition preventing intramuscular injection as bleeding or coagulation disorder.
• Malignancies within previous 5 years (excluding non-melanoma skin cancer) or lymphoproliferative disorders.
• Prior/concomitant therapy
• 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 vaccine (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 vaccine administration, with the exception of non-MF59 adjuvanted influenza vaccines and pneumococcal vaccines which may be administered ≥15 days preceding or following any study vaccine dose.

• Planned administration/administration of a vaccine adjuvanted with the following adjuvants AS01, AS02, AS03, AS04 and MF59 in the period starting 6 months before the first dose of study vaccine, and ending at the second blood draw (i.e. approximately 1 month after the administration of the last dose of NTHi-Mcat vaccine). The following non-exhaustive list should be considered as criteria for exclusion: Prepandrix, Adjupanrix, Shingrix, Fendrix, Cervarix, FluAd, Chiromas, Gripguard.
• Previous vaccination with any vaccine containing NTHi and/or Mcat antigens
• Previous vaccination with Shingrix; (either registered product or participation in a previous vaccine study).
• Previous vaccination with HZ live-attenuated vaccine (ZVL)) (either registered product or participation in a previous vaccine study) within the 2 months of the first study visit (Day 1).
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose, and ending at the second blood draw. (i.e. approximately 1 month after the administration of the last dose of NTHi-Mcat vaccine). For corticosteroids, this will mean prednisone ≥5 mg/day (for adult subjects), or equivalent. Only topical steroids are allowed.
• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study vaccine or planned administration starting from Day 1 and ending at the second blood draw (i.e. approximately 1 month after the planned administration of the second dose of NTHi-Mcat vaccine).
• Prior/concurrent clinical study experience
• 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 (drug or medical device).
• Other exclusions:
• Pregnant or lactating female,
• Female planning to become pregnant or planning to discontinue contraceptive precautions,
• Current alcoholism and/or drug abuse,
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study
• Any study personnel or immediate dependents, family, or household member.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tartu, , Estonia

GSK Investigational Site

Tartu, , Estonia

GSK Investigational Site

Helsinki, , Finland

GSK Investigational Site

Jyväskylä, , Finland

GSK Investigational Site

Tampere, , Finland

GSK Investigational Site

Turku, , Finland

GSK Investigational Site

Montpellier, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Rennes, , France

GSK Investigational Site

Pisa, Tuscany, Italy

GSK Investigational Site

Verona, Veneto, Italy

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

Countries

Estonia; Finland; France; Italy; Spain

References

Galgani I, Poder A, Jogi R, Anttila VJ, Milleri S, Borobia AM, Launay O, Testa M, Casula D, Grassano L, Tasciotti A, Dozot M, Arora AK. Immunogenicity and safety of the non-typable Haemophilus influenzae-Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial. Hum Vaccin Immunother. 2023 Dec 31;19(1):2187194. doi: 10.1080/21645515.2023.2187194. Epub 2023 Mar 28.

Reference Type: BACKGROUND

PMID: 36974988 (View on PubMed)

de Oliveira Gomes J, Gagliardi AM, Andriolo BN, Torloni MR, Andriolo RB, Puga MEDS, Canteiro Cruz E. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2023 Oct 2;10(10):CD008858. doi: 10.1002/14651858.CD008858.pub5.

Reference Type: DERIVED

PMID: 37781954 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002977-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

209538

Identifier Type: -

Identifier Source: org_study_id