Clinical Trials Register

Summary
EudraCT Number:	2017-000880-34
Sponsor's Protocol Code Number:	207489
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-07-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2017-000880-34

A.3

Full title of the trial

A Phase IIB, randomised, observer-blind, placebo-controlled, multi-centre study to evaluate the efficacy, safety, reactogenicity and immunogenicity of the GSK Biologicals’ investigational vaccine GSK3277511A when administered intramuscularly according to a 0, 2 month schedule in COPD patients aged 40 to 80 years with a previous history of acute exacerbation (AECOPD).

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to test if the vaccine is working well in Chronic Obstructive Pulmonary Disease (COPD) patients aged 40 to 80 years old to reduce episodes of worsening symptoms and to gather further information on safety and immune response.

A.3.2

Name or abbreviated title of the trial where available

NTHI MCAT-002

A.4.1

Sponsor's protocol code number

207489

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Biologicals
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline Biologicals
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Biologicals
B.5.2	Functional name of contact point	Clinical Disclosure Advisor
B.5.3	Address:
B.5.3.1	Street Address	Rue de l’Institut, 89
B.5.3.2	Town/ city	Rixensart
B.5.3.3	Post code	1330
B.5.3.4	Country	Belgium
B.5.4	Telephone number	442089904466
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	NTHI-Mcat 10-10-3
D.3.2	Product code	NTHI-Mcat 10-10-3
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.2	Current sponsor code	PD
D.3.9.3	Other descriptive name	Recombinant Non-typeable Haemophilus influenzae Protein D (PD)
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.2	Current sponsor code	PE-PilA
D.3.9.3	Other descriptive name	Recombinant Non-typeable Haemophilus influenzae PE and PilA fusion protein
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.2	Current sponsor code	UspA2
D.3.9.3	Other descriptive name	Ubiquitous Surface Protein A2 (UspA2) from Moraxella catarrhalis
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3.3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Obstructive Pulmonary Disease (COPD)

E.1.1.1

Medical condition in easily understood language

COPD is a lung disease that makes it hard to breathe. It is caused by damage to the lungs over many years, usually from smoking.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10009033
E.1.2	Term	Chronic obstructive pulmonary disease
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess efficacy of the investigational vaccine as compared to the placebo control with respect to the rate of moderate and severe acute exacerbations of COPD (AECOPDs).

E.2.2

Secondary objectives of the trial

• To describe the safety and reactogenicity of the investigational vaccine.
• To assess efficacy of the investigational vaccine as compared to the placebo control with respect to the rate of all AECOPDs and by severity (i.e. mild, moderate or severe).
• To assess efficacy of the investigational vaccine as compared to the placebo control with respect to the rate of all AECOPDs and by severity (i.e. mild, moderate or severe) associated with NTHi and/or Mcat detected by polymerase chain reaction (PCR).
• To evaluate the humoral immunogenicity of the investigational vaccine.
• To evaluate the cellular immunogenicity of the investigational vaccine.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. electronic Diary Card completion, number of blood draws, sputum sampling, pre- and post-bronchodilator spirometry, return for follow-up visits).
• 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.
• Confirmed diagnosis of COPD (based on post-bronchodilator spirometry) with forced expiratory volume in 1 second (FEV1) over forced vital capacity (FVC) ratio (FEV1/FVC) < 0.7, AND FEV1 < 80% predicted (GOLD 2, 3 and 4).
• Current or former smoker with a cigarette smoking history of ≥ 10 pack-years.
• Stable COPD patient* with documented history** (e.g. medical record verification) of at least 1 moderate or severe AECOPD within the 12 months before Screening.
* Patient for whom the last episode of AECOPD is resolved for at least 30 days at the time of first vaccination.
** A documented history of a COPD exacerbation (e.g. medical record verification) is a medical record of worsening COPD symptoms that required systemic/oral corticosteroids and/or antibiotics (for a moderate exacerbation) or hospitalization (for a severe exacerbation). Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence (color). Subject verbal reports are not acceptable.
• Capable of complying with the daily electronic Diary Card completion throughout the study period, according to investigator’s judgement at Visit 1.
• 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.

E.4

Principal exclusion criteria

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 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.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Administration of immunoglobulins or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• 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, 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 (pharmaceutical product or device).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose (e.g. methotrexate).
• Administration of systemic corticosteroids (prednisone ≥10 mg/day, or equivalent) within the 30 days before first vaccination.
- Subjects who received systemic corticosteroids within this period may be enrolled at a later date if enrolment is still open.
- Inhaled and topical steroids are allowed.
• Administration of systemic antibiotics within the 30 days before first vaccination.
- Subjects who received systemic antibiotics within this period may be enrolled at a later date if enrolment is still open.
• Chronic use of antibiotics for prevention of AECOPD (e.g. azithromycin).
• Acute disease and/or fever at the time of first vaccination.
- Fever is defined as temperature >=37.5°C/99.5°F. 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.
• Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen therapy >3L/min (Oxygen use ≤3L/min flow is not exclusionary).
• Planned lung transplantation.
• Lung resection: Subjects with planned lung volume reduction surgery during the study or within the 12 months prior to first vaccination.
• Diagnosis of α-1 antitrypsin deficiency as the underlying cause of COPD.
• Diagnosed with a respiratory disorder other than COPD at time of enrolment (such as sarcoidosis, active tuberculosis, clinically significant bronchiectasis, clinically significant lung fibrosis, clinically significant pulmonary embolism, clinically significant pneumothorax, current diagnosis of asthma in the opinion of the investigator), or chest X-ray/ CT scan revealing evidence of clinically significant abnormalities not believed to be due to the presence of COPD. Subjects with allergic rhinitis do not need to be excluded and may be enrolled at the discretion of the investigator.
• History of immune-mediated disease other than COPD.
• Previous vaccination with any vaccine containing NTHi and/ or Mcat antigens.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines and/ or the bronchodilator used for spirometry assessment during the study.
• Contraindication for spirometry testing (such as recent eye surgery, recent thoracic or abdominal surgery procedures, unstable cardiovascular status, recent myocardial infarction or pulmonary embolism).
• Unstable or life threatening cardiac disease: subjects with any of the following at Screening (Visit 1) would be excluded:
- Myocardial infarction or unstable angina in the last 6 months.
- Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months.
- NYHA Class IV Heart failure.
• Malignancies within the previous 5 years (excluding non-melanotic skin cancer and carcinoma in situ of the cervix, if considered cured) or lymphoproliferative disorder.
• Any known disease or condition likely to cause death during the study period.
• Pregnant or lactating female.
• Current alcoholism and/or drug abuse.
• Other condition which the investigator judges may put the safety of the subject at risk through study participation or which may interfere with the study findings (e.g. anaemia, patient on dialysis).
• Planned move to a location that will complicate participation in the trial through study end.

E.5 End points

E.5.1

Primary end point(s)

Rate of moderate and severe AECOPD (any cause)

E.5.1.1

Timepoint(s) of evaluation of this end point

From 1 month post-Dose 2 up to study end at Day 451.

E.5.2

Secondary end point(s)

1) Occurrence of each solicited local adverse event (AE).
2) Occurrence of each solicited general AE.
3) Occurrence of any unsolicited AE.
4) Occurrence of any potential immune-mediated disease (pIMD).
5) Occurrence of any serious adverse event (SAE).
6) Incidence rate of moderate and severe AECOPD cases in vaccinated and control subjects.
7) Incidence rate of all AECOPD cases in vaccinated and control subjects.
8) Incidence rate of all AECOPD cases in vaccinated and control subjects by severity.
9) Time to first moderate or severe AECOPD.
10) Time to first AECOPD of any severity.
11) Time to first AECOPD, by severity.
12) Duration of moderate and severe AECOPDs.
13) Duration of AECOPDs of any severity.
14) Duration of AECOPDs, by severity.
15) Rate of NTHi-associated and/ or Mcat-associated moderate and severe AECOPD.
16) Rate of NTHi-associated and/ or Mcat-associated any severity AECOPD.
17) Rate of NTHi-associated and/ or Mcat-associated AECOPD, by severity.
18) Time to first moderate or severe NTHi-associated and/ or Mcat-associated AECOPD.
19) Time to first NTHi-associated and/or Mcat-associated AECOPD of any severity.
20) Time to first NTHi-associated and/or Mcat-associated AECOPD, by severity.
21) Duration of moderate and severe NTHi-associated and Mcat-associated AECOPD.
22) Duration of NTHi-associated and/or Mcat-associated AECOPDs of any severity.
23) Duration of NTHi-associated and/or Mcat-associated AECOPD, by severity.
24) Anti-PD, anti-PE, anti-PilA and anti-UspA2 total IgG antibody concentrations as measured by ELISA, in all subjects.
25) NTHi-specific and Mcat- specific cell-mediated immune re-sponses as measured by flow cytometry ICS (frequency of specific CD4+ T-cells expressing two or more markers, such as interleukin (IL)-2, IL-13, IL-17, interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α), and CD40 ligand (CD40L), in a sub-cohort of subjects.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) and 2) During the 7-day follow-up period (Days 1-7) after each vac-cination
3) During the 30-day follow-up period (Days 1-30) after each vaccination.
4) and 5) From first vaccination (Day 1) up to Study end, at Day 451.
6), 7) and 8) During 3, 6 and 9 months observation starting 1 month post-Dose 2.
9), 10), 11), 12), 13), 14), 18), 19), 20), 21), 22) and 23) Up to Study end, at Day 451.
15), 16) and 17) Over a period starting 1 month post-Dose 2 and lasting for 1 year.
24) at Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
25) at Day 1, Day 91, Day 271 and at Day 451

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Humoral and cell mediated immunogenicity

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

observer blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Canada

France

Germany

Italy

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last testing results released of samples collected up to Visit 8 (Day 451).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

300

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

369

F.4.2.2

In the whole clinical trial

600

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the subjects have ended their participation in this trial they will continue with standard care.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-08-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-07

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials