Respiratory DisordersPhase 2NCT03894969
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
A Phase 2 study testing GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E and Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A) in people with Respiratory Disorders, run by GlaxoSmithKline at 14 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Respiratory Disorders
- What is being tested?
- GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E and Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 541 participants
- Where
- 14 sitesin 5 countries
- Study dates
- 23 Apr 2019to 13 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
- The investigator will exercise his/her medical and scientific judgement in deciding whether other diseases have an autoimmune origin and thus meet the exclusion criteria.
- 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).
Show all 28Show fewer
- 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.
- Note: For M59 adjuvanted flu vaccine and for any vaccine containing novel adjuvant refer to exclusion criteria below.
- 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.
Trial locations and contacts
14 sites in 5 countries.
14 sites in 5 countries
Finland4 sites
GSK Investigational Site
Helsinki, 00029
GSK Investigational Site
Jyväskylä, 40100
GSK Investigational Site
Tampere, FI-33100
GSK Investigational Site
Turku, 20100
Estonia3 sites
GSK Investigational Site
Tallinn, 10117
GSK Investigational Site
Tartu, 50106
GSK Investigational Site
Tartu, 51014
France3 sites
GSK Investigational Site
Montpellier, 34295
GSK Investigational Site
Paris, 75679
GSK Investigational Site
Rennes, 35033
Italy2 sites
GSK Investigational Site
Pisa, Tuscany, 56126
GSK Investigational Site
Verona, Veneto, 37134
Spain2 sites
GSK Investigational Site
Madrid, 28006
GSK Investigational Site
Madrid, 28046
About this study
Official title: Immunogenicity and Safety Study of GSK's Investigational Vaccine (GSK3277511A) When Administered in Healthy Smokers and Ex-smokers Following Receipt of Shingrix Vaccine
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
- Being tested
- GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E, Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)
- Keywords
- Immunogenicity, Chronic obstructive pulmonary disease (COPD), Non-typeable Haemophilus influenza, Moraxella catarrhalis, Shingrix, Herpes Zoster, Adjuvanted vaccines, Safety
- Medical subject headings
- Respiration Disorders, Pulmonary Disease, Chronic Obstructive, Herpes Zoster
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01EBiological
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)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
| Study group | Role | What they receive |
|---|---|---|
| Sh_NTHi-Mcat_1 Group | Experimental | 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. Receives: Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E; Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A) |
| Sh_NTHi-Mcat_3 Group | Experimental | 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. Receives: Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E; Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A) |
| Sh_NTHi-Mcat_6 Group | Experimental | 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. Receives: Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E; Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A) |
| NTHi-Mcat Group | Active comparator | 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. Receives: Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E |
| Shingrix-Only Group | Experimental | 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. Receives: Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-Protein D (PD), Anti-Protein E (PE), Anti-type IV Pili Subunit (PilA) and Anti-ubiquitous Surface Protein A2 of Moraxella Catarrhalis (UspA2) Adjusted Geometric Mean Concentrations (GMCs), One-month Post Dose-2 of NTHi-Mcat Vaccine
Antibody concentrations as measured by ELISA (Enzyme-linked immunosorbent assay) and expressed as adjusted (ANCOVA model) GMCs in ELISA units per milliliter (EU/mL). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively. The ANCOVA model includes study group, smoking status (current or former), age category (50-59, 60-69, 70-80 years of age) and center as factors and the antibody concentration before Dose 1 as covariate. As per protocol set (PPS) sample size was not met in Sh_NTHi_Mcat_3 and Sh_NTHi-Mcat_6 groups then timeframe was adapted as follows: At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181 in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group)
Measured: At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181, in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group)
Secondary outcomes (13)
Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibody Concentrations in Terms of GMCs, Before First NTHi-Mcat Vaccine
GMCs and their 95% CI for each of the antibodies, as measured by ELISA, were calculated (the GMCs were computed by taking the Anti-log of the mean of the log concentration transformations)
Measured: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 for Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 for NTHi-Mcat group)
Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibody Concentrations in Terms of GMCs, One-month Post Dose-2 of NTHi-Mcat Vaccine
GMCs and their 95% CI for each of the antibodies, as measured by ELISA, were calculated (the GMCs were computed by taking the Anti-log of the mean of the log concentration transformations) before the first dose of NTHi-Mcat vaccine
Measured: At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
Percentage of Seropositive Subjects for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibodies Before First NTHi-Mcat Vaccine
A seropositive subject is defined as a subject whose Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibody concentrations are greater than or equal to the assay cut-off value. Seropositivity rates with 95% CI is defined using the assay lower limit of quantification (LLOQ). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively
Measured: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group)
Percentage of Subjects Seropositive for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibodies, One-month Post Dose-2 of NTHi-Mcat Vaccine
A seropositive subject is defined as a subject whose Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibody concentrations are greater than or equal to the assay cut-off value. Seropositivity rates with 95% CI are defined using the assay (LLOQ). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively
Measured: At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
Frequency of Specific Cluster of Differentiation 4 (CD4+) T-cells Against NTHi and Mcat Antigens for Evaluation of Cell-mediated Immune (CMI) Response, Before First Dose of NTHi-Mcat Vaccine
Frequency of specific CD4+ T-cells was measured by flow cytometry intracellular cytokine staining (ICS) expressing at least 2 different markers among CD40 Ligand (CD40L), interleukin (IL)-2, IL-13, IL-17, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), upon in vitro stimulation
Measured: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group)
Frequency of CD4+ T-cells Against NTHi and Mcat Antigens for Evaluation of CMI Response, at One-month Post Dose 2 of NTHi-Mcat Vaccine
Frequency of specific CD4+ T-cells was measured by flow cytometry ICS expressing at least 2 different markers among CD40L, IL-2, IL-13, IL-17, TNF-α and IFN-γ, upon in vitro stimulation
Measured: At one month after second dose of NTHi-Mcat vaccine (Day 181, Day 241 and Day 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
Percentage of Subjects With Reported Solicited Local Adverse Event (AE)
The percentage of subjects with at least one local solicited AE, regardless of intensity, during the 7-day follow-up period after each NTHi-Mcat vaccine dose, are reported by study group. Assessed local symptoms were pain, redness and swelling. Any local injection site redness/swelling is scored as follows: diameter >=20 milli-meters
Measured: During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
Percentage of Subjects With Reported Solicited General AE
The percentage of subjects with at least one general solicited AE, regardless of intensity, during the 7-day follow-up period after each NTHi-Mcat vaccine dose, are reported by study group. Assessed solicited general symptoms were Fatigue, Gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), Headache, Myalgia, Chills and Fever (oral cavity or axillary route - temperature equal or higher than [>=] 37.5 degrees Celsius [°C])
Measured: During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
Percentage of Subjects With Any Unsolicited AE
An unsolicited adverse event is an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject who has signed the informed consent. The percentage of subjects with at least one unsolicited AE, regardless of intensity or relationship to vaccination, during the 30-day follow-up period after any NTHi-Mcat vaccine dose are reported for each group. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event
Measured: During the 30-day follow-up period (i.e. day of vaccination and 29 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
Percentage of Subjects With Any Serious Adverse Event (SAE) During Epoch 001
The percentage of subjects with at least one SAE, regardless of intensity or relationship to vaccination, from Day 1 up to and including Day 331, were reported for each group 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
Measured: From Day 1 up to and including Day 331 (Epoch 001)
Percentage of Subjects With Any Potential Immune-mediated Diseases (pIMD's) During Epoch 001
pIMD's 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.
Measured: From Day 1 up to and including Day 331 (Epoch 001)
Percentage of Subjects With Any SAE During Epoch 002
The percentage of subjects with at least one SAE, regardless of intensity or relationship to vaccination, from Day 332 up to and including Day 661, are reported for each group. An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, requires 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.
Measured: From Day 332 up to and including Day 661 (Epoch 002)
Percentage of Subjects With Any pIMD's During Epoch 002
pIMD's 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
Measured: From Day 332 up to and including Day 661 (Epoch 002)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2019
- Study start23 Apr 2019
- Primary completion31 Aug 2020
- Study completion13 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Respiratory DisordersStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 541 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03894969
- Sponsor's protocol ID
- 209538
- Other IDs
- 2018-002977-24, 2018
- Status last verified
- Sep 2024
- First submitted
- 27 Mar 2019
- Last updated
- 23 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf
Publications
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.
PubMed 36974988de 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.
PubMed 37781954
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenicity and Safety Study of GSK's Investigational Vaccine (GSK3277511A) When Administered in Healthy Smokers and Ex-smokers Following Receipt of Shingrix Vaccine
- ClinicalTrials.gov ID
- NCT03894969
- Acronym / sponsor ID
- 209538
- Conditions
- Respiratory Disorders
- Keywords
- Immunogenicity, Chronic obstructive pulmonary disease (COPD), Non-typeable Haemophilus influenza, Moraxella catarrhalis, Shingrix, Herpes Zoster, Adjuvanted vaccines, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 541 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 23 Apr 2019 (actual)
- Primary completion
- 31 Aug 2020 (actual)
- Study completion
- 13 Aug 2021 (actual)
- First posted
- 29 Mar 2019 (actual)
- Results
- Posted 27 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Sh_NTHi-Mcat_1 Group | Experimental | Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E, Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)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. |
| Sh_NTHi-Mcat_3 Group | Experimental | Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E, Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)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. |
| Sh_NTHi-Mcat_6 Group | Experimental | Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E, Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)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. |
| NTHi-Mcat Group | Active comparator | Biological: GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01ESubjects enrolled in this group received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 1 and Day 61. |
| Shingrix-Only Group | Experimental | Biological: Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A)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. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (28 listed)
- 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.
- The investigator will exercise his/her medical and scientific judgement in deciding whether other diseases have an autoimmune origin and thus meet the exclusion criteria.
- Diagnosis of COPD regardless of severity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E2 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 | Biological | NTHi-Mcat Group, Sh_NTHi-Mcat_1 Group, Sh_NTHi-Mcat_3 Group, Sh_NTHi-Mcat_6 Group |
| 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 | Biological | Sh_NTHi-Mcat_1 Group, Sh_NTHi-Mcat_3 Group, Sh_NTHi-Mcat_6 Group, Shingrix-Only Group |
Primary outcome
Anti-Protein D (PD), Anti-Protein E (PE), Anti-type IV Pili Subunit (PilA) and Anti-ubiquitous Surface Protein A2 of Moraxella Catarrhalis (UspA2) Adjusted Geometric Mean Concentrations (GMCs), One-month Post Dose-2 of NTHi-Mcat Vaccine
Time frame: At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181, in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group)
Antibody concentrations as measured by ELISA (Enzyme-linked immunosorbent assay) and expressed as adjusted (ANCOVA model) GMCs in ELISA units per milliliter (EU/mL). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively. The ANCOVA model includes study group, smoking status (current or former), age category (50-59, 60-69, 70-80 years of age) and center as factors and the antibody concentration before Dose 1 as covariate. As per protocol set (PPS) sample size was not met in Sh_NTHi_Mcat_3 and Sh_NTHi-Mcat_6 groups then timeframe was adapted as follows: At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181 in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group)
13 secondary outcomes
Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibody Concentrations in Terms of GMCs, Before First NTHi-Mcat Vaccine
Time frame: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 for Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 for NTHi-Mcat group)
Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibody Concentrations in Terms of GMCs, One-month Post Dose-2 of NTHi-Mcat Vaccine
Time frame: At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
Percentage of Seropositive Subjects for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibodies Before First NTHi-Mcat Vaccine
Time frame: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group)
Percentage of Subjects Seropositive for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 Antibodies, One-month Post Dose-2 of NTHi-Mcat Vaccine
Time frame: At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
Frequency of Specific Cluster of Differentiation 4 (CD4+) T-cells Against NTHi and Mcat Antigens for Evaluation of Cell-mediated Immune (CMI) Response, Before First Dose of NTHi-Mcat Vaccine
Time frame: Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group)
Frequency of CD4+ T-cells Against NTHi and Mcat Antigens for Evaluation of CMI Response, at One-month Post Dose 2 of NTHi-Mcat Vaccine
Time frame: At one month after second dose of NTHi-Mcat vaccine (Day 181, Day 241 and Day 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
Percentage of Subjects With Reported Solicited Local Adverse Event (AE)
Time frame: During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
Percentage of Subjects With Reported Solicited General AE
Time frame: During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
Percentage of Subjects With Any Unsolicited AE
Time frame: During the 30-day follow-up period (i.e. day of vaccination and 29 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
Percentage of Subjects With Any Serious Adverse Event (SAE) During Epoch 001
Time frame: From Day 1 up to and including Day 331 (Epoch 001)
Percentage of Subjects With Any Potential Immune-mediated Diseases (pIMD's) During Epoch 001
Time frame: From Day 1 up to and including Day 331 (Epoch 001)
Percentage of Subjects With Any SAE During Epoch 002
Time frame: From Day 332 up to and including Day 661 (Epoch 002)
Percentage of Subjects With Any pIMD's During Epoch 002
Time frame: From Day 332 up to and including Day 661 (Epoch 002)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 36974988Galgani 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.
- Derived from this study: PubMed 37781954de 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.
- Individual participant dataSharing planned: Yes. GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf
Related trials for Respiratory Disorders
RecruitingObservational study
Collection of Lung Fluid and Tissue Samples for Research
Leukocyte Disorders, Respiratory Tract Diseases
Not yet recruiting
Physical Activity, Sleep Quality, and Respiratory Function in Obstructive Sleep Apnea
Obstructive Sleep Apnea, Sleep Quality
RecruitingObservational study
Product Surveillance Registry
Cardiac Rhythm Disorders, Urological Disorders
Not yet recruitingPhase 3
Safety and Analgesic Efficacy of the Biased μ-Opioid Receptor Agonist Tegileridine for Post-Operative Analgesia in Patients Undergoing Bariatric Surgery
Pain Management, Overweight , Obesity
Not yet recruiting
Optimizing Dysphagia Treatment Delivery in Acute Care: A Hybrid Efficacy Implementation Trial
Dysphagia, Critical Illness
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
14 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK's investigational non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) multi-antigen vaccine (GSK3277511A) adjuvanted with AS01E and Shingrix GSK's lyophilized formulation of the herpes zoster (HZ) vaccine (GSK1437173A) in people with Respiratory Disorders, run by GlaxoSmithKline at 14 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Finland, Estonia, France, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti-Protein D (PD), Anti-Protein E (PE), Anti-type IV Pili Subunit (PilA) and Anti-ubiquitous Surface Protein A2 of Moraxella Catarrhalis (UspA2) Adjusted Geometric Mean Concentrations (GMCs), One-month Post Dose-2 of NTHi-Mcat Vaccine (time frame: At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181, in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03894969, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024; AzTrials last refreshed its copy on 26 Oct 2026.