Clinical Trials Register

Summary
EudraCT Number:	2020-002356-20
Sponsor's Protocol Code Number:	CLI-05993BA1-08
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-03-11
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

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2020-002356-20

A.3

Full title of the trial

Open label, prospective study to evaluate the effect of step-up from non-extrafine ICS/LABA DPI to extra fine triple therapy with CHF5993 DPI on airway geometry and lung ventilation using FRI in subjects with advanced COPD

A.3.1

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

A.4.1

Sponsor's protocol code number

CLI-05993BA1-08

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	Chiesi Farmaceutici S.p.A.
B.1.3.4	Country	Italy
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	Chiesi Farmaceutici S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Chiesi Farmaceutici S.p.A.
B.5.2	Functional name of contact point	Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Largo Francesco Belloli 11/A
B.5.3.2	Town/ city	Parma
B.5.3.3	Post code	43122
B.5.3.4	Country	Italy
B.5.4	Telephone number	+3905211689318
B.5.6	E-mail	clinicaltrials_info@chiesi.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	CHF 5993 DPI 100/6/12,5
D.3.2	Product code	CHF 5993 DPI
D.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BECLOMETASONE DIPROPIONATE
D.3.9.1	CAS number	5534-09-8
D.3.9.2	Current sponsor code	BDP
D.3.9.4	EV Substance Code	SUB00681MIG
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	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FORMOTEROL FUMARATE
D.3.9.1	CAS number	43229-80-7
D.3.9.2	Current sponsor code	FF
D.3.9.4	EV Substance Code	SUB02257MIG
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	6
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Glycopyrronium bromide
D.3.9.1	CAS number	596-51-0
D.3.9.3	Other descriptive name	GB
D.3.9.4	EV Substance Code	SUB07951MIG
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	12.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COPD (Chronic Obstructive Pulmonary Disease)

E.1.1.1

Medical condition in easily understood language

difficulty in breathing

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD
E.1.2	System Organ Class	100000004855

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 the effect of stepping-up from SERETIDE™ DISKUS™ (fluticasone propionate/salmeterol or FP/SLM 500/50 µg) DPI to extra fine CHF 5993 (BDP/FF/GB 100/6/12.5 µg) DPI on airway geometry and lung ventilation

E.2.2

Secondary objectives of the trial

To assess therapeutic aerosol particles deposition, lung function following a switch from FP/SLM 500/50 µg DPI (SERETIDE™ DISKUS™) to extra fine BDP/FF/GB 100/6/12.5 µg DPI (CHF5993).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject’s signed Informed Consent Form obtained prior to any study-related procedure;
2. Male or female ≥ 40 years of age;
3. Current smokers and/or ex-smokers of at least 10 pack-years
4. Established diagnosis of COPD according to the 2020 GOLD Report, prior to the Screening visit (V1);
5. Post-BD FEV1/FVC < 0.7 and FEV1 ≤ 60% of predicted at V1
6. On a stable dose of any non-extrafine ICS/LABA DPI twice daily regimen for at least 8 weeks before screening;
7. Presence of lung hyperinflation based on the increase of Total Lung Capacity (TLC) exceeding either the upper limit of normal (ULN) or an empiric 120% of predicted, and/or a plethysmographic functional residual capacity (FRC) exceeding either ULN or 120 % of predicted;
8. Symptomatic subjects with CAT score ≥ 10 at V1 and V2;
9. Documented history of ≥ 1 moderate or severe COPD exacerbation in the previous 12 months prior to V1;
10. To have a cooperative attitude and the ability to be trained and use correctly the Dry Powder Inhalers (DPI);
11. To have a cooperative attitude and the ability to perform the required outcomes measurements (e.g. spirometry manoeuvres in sitting and supine position) and the ability to understand the risks involved;
12. WOCBP fulfilling one of the following criteria:
a. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up visit or
b. WOCBP with non-fertile male partners (contraception is not required in this case)
13. Female subjects of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile; e.g. amenorrhea for ≥ 12 consecutive months without alternative medical cause).

E.4

Principal exclusion criteria

1. Pregnant or lactating woman;
2. Exacerbations defined as a sustained and acute deterioration of subject’s symptoms and signs (dyspnoea, cough and/or sputum production/purulence) that are either moderate, i.e. require treatment with systemic (oral/IV/IM) corticosteroids and/or antibiotics, or severe, i.e. require hospitalization, if their associated treatment/hospitalization occurred within the 30 days before V1 (or 4 weeks in case the event was treated with just systemic corticosteroids) or if the event is recorded during the run-in period;
3. A current asthma diagnosis;
4. Respiratory disorders other than COPD
5. Cardiovascular diseases
6. Evidence or history of other concurrent disease
7. Medical history or current diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that in the opinion of the Investigator would have prevented use of anticholinergic agents;
8. History of lung transplant or lung reduction surgery;
9. ECG criteria: any clinically significant abnormal 12-lead ECG that in the investigator's opinion would affect efficacy or safety evaluation or place the subjects at risk. Male subjects with a QTcF >450msec and female subjects with a QTcF > 470msec at V1 are not eligible;
10. Laboratory abnormalities
11. Alcohol/drug abuse
12. Participation to investigational trial: subjects who have received any investigational drug within the 30 days or a more appropriate time as determined by the investigator (e.g. approximately 5 half-lives of the investigational drug, whatever is longer);
13. Contra-indications to IMPs, based on investigator judgement;
14. Hypersensitivity: history of hypersensitivity to any of the study medications components or a history of other allergy that in the opinion of the investigator contraindicates the subject's participation;
15. Subjects mentally or legally incapacitated or subjects accommodated in an establishment as a result of an official or judicial order;
16. Documented COVID-19 diagnosis or its complications which have not resolved within 14 days prior to screening;
17. Positive molecular COVID-19 test within the last 72 hours before the remaining of screening activities.

E.5 End points

E.5.1

Primary end point(s)

• Percentage change from baseline (pre-dose V2) to pre-dose in untrimmed specific airway volume (siVaw) upon inspiration (at Total Lung Capacity, TLC) at Visit 3
• Percentage change from baseline (pre-dose V2) to pre-dose in trimmed specific airway resistance (siRaw) upon inspiration (at TLC) at Visit 3

E.5.1.1

Timepoint(s) of evaluation of this end point

each period of the study

E.5.2

Secondary end point(s)

Values at pre-dose and post-dose for the following FRI parameters:
•siVaw upon expiration (at Functional Residual Capacity, FRC)
•siRaw upon expiration (at FRC)
•ventilation mapping
•perfusion mapping
•airway wall thickness upon inspiration (at TLC)
•imaged lobe and lung volumes at TLC and FRC
•air trapping at FRC
•low attenuation score at TLC
•Percentile 15th at TLC
•Regional lung deposition
In addition, pre-dose spirometry, body plethysmography and CAT will be
assessed at Visit 2 and Visit 3.

safety variabels:
•Adverse Events (AEs) and Adverse Drug Reactions (ADRs)
•Vital signs (systolic and diastolic blood pressure)

E.5.2.1

Timepoint(s) of evaluation of this end point

throughout the trial

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

prospective

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

comparison to baseline (run-in medication)

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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)

see protocol

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

2021-04-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-01-03

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