Clinical Trials Register

Summary
EudraCT Number:	2020-003666-40
Sponsor's Protocol Code Number:	CLI-06001AA1-04
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-02-04
Trial 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

Czechia - SUKL

A.2

EudraCT number

2020-003666-40

A.3

Full title of the trial

A 52-week, randomized, double-blind, placebo-controlled, parallel-group, study to evaluate the efficacy and safety of two doses of CHF6001 DPI add-on to maintenance triple therapy in subjects with Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis.

52týdenní, randomizované, dvojitě zaslepené, placebem kontrolované klinické hodnocení s paralelními skupinami hodnotící účinnost a bezpečnost dvou dávek přípravku CHF6001 DPI přidaného k udržovací trojité terapii u pacientů s chronickou obstrukční plicní nemocí (CHOPN) a chronickou bronchitidou

A.3.1

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

The efficacy and the safety of two doses of CHF6001 for the treatment of Chronic Obstructive Pulmonary Disease (COPD).

A.3.2

Name or abbreviated title of the trial where available

PILASTER

A.4.1

Sponsor's protocol code number

CLI-06001AA1-04

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04636801

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	Via Palermo 26/A
B.5.3.2	Town/ city	Parma
B.5.3.3	Post code	43122
B.5.3.4	Country	Italy
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	CHF6001 NEXThaler 400 μg/20 mg
D.3.2	Product code	CHF6001
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	Tanimilast
D.3.9.1	CAS number	1239278-59-1
D.3.9.2	Current sponsor code	CHF 6001
D.3.9.3	Other descriptive name	CHF 6001.00
D.3.9.4	EV Substance Code	SUB180242
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	400
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.IMP: 2
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	CHF6001 NEXThaler 800 μg/20 mg
D.3.2	Product code	CHF6001
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	Tanimilast
D.3.9.1	CAS number	1239278-59-1
D.3.9.2	Current sponsor code	CHF 6001
D.3.9.3	Other descriptive name	CHF 6001.00
D.3.9.4	EV Substance Code	SUB180242
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	800
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder
D.8.4	Route of administration of the placebo	Inhalation 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) and Chronic Bronchitis

E.1.1.1

Medical condition in easily understood language

Chronic Obstructive Pulmonary Disease (COPD)

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 evaluate the efficacy of two doses of CHF6001 add-on to maintenance triple therapy (ICS, LABA, LAMA) to reduce the rate of moderate and severe exacerbations after 52 weeks of treatment in comparison with maintenance triple therapy (i.e. placebo arm).

E.2.2

Secondary objectives of the trial

To evaluate
-the efficacy of the two doses of CHF6001 add-on to maintenance triple therapy on health related quality of life after 52 weeks of
treatment (change in SGRQ total score).
-the efficacy of the two doses of CHF6001 add-on to maintenance triple therapy on lung function, health-related quality of life, severe exacerbations in the pooled analysis of CLI-06001AA1-04 Main cohort
(excluding subjects enrolled in China) and CLI-06001AA1-05 studies and other clinical outcome measures in comparison with maintenance triple therapy
-the safety and tolerability of the two doses of CHF6001

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacokinetic variables
A subset of about 240 randomized subjects (80 expected in each treatment group) will be selected in order to reach about 60 evaluable subjects for each CHF6001 dose treatment. PK parameters will be estimated by measurement of CHF6001 plasma levels in a subset of subjects at different timepoints (pre-dose and over 8 hours post-dose) on V2 (Day 0) and V5 (week 26) and at pre-dose only on V4 (week12) and V6 (week 40).
Exclusion criteria for the subset of subjects undergoing PK assessments
1. Subjects with unsuitable veins for repeated venopuncture.
2. Blood donation (excluding plasma donations) or blood loss equal or more than 450 mL less than 2 months prior to screening

E.3

Principal inclusion criteria

1.Males and females aged ≥ 40 years with written informed consent obtained prior to any study-related procedure.
2.Females are eligible to enter the study if they are of
a.non-childbearing potential
or
b.childbearing potential, they must have a negative pregnancy test at screening and must agree to use one or more of the acceptable contraceptive measures.
3.Subjects with an established diagnosis of COPD with chronic bronchitis
4.Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years.
5.A post-bronchodilator FEV1 < 60% of the subject predicted normal value and a post-bronchodilator FEV1/FVC ratio < 0.7 after 400µg (4 puffs x 100µg) of salbutamol pMDI or equivalent dose of albuterol pMDI in the US.
6.A documented history (e.g. medical record verification) of at least one moderate or severe COPD exacerbation in previous year.
7.Symptomatic subject at screening defined as having a CAT score ≥10.
8.Subjects prescribed with maintenance triple therapy (free or fixed combination of ICS, LABA, LAMA) according to GOLD 2020
recommendations for at least 12 months prior to screening and receiving regular maintenance triple therapy for at least 3 months prior to the
Screening visit.
9.Subjects are willing and able to be trained to use correctly the DPI inhalers (NEXThaler®).
10.Subjects are willing and able to be trained to use correctly the electronic devices with COPD questionnaires, to understand and to perform required outcome measurements of the protocol (e.g. spirometry manoeuvres etc.) and ability to understand the risks involved.

E.4

Principal exclusion criteria

1.Subjects with a diagnosis of current asthma.
2.Subjects with a moderate or severe COPD exacerbation 4 weeks prior to study entry and during run-in period.
3.Pregnant and lactating women.
4.Subjects requiring long term (at least 15 hours daily) oxygen therapy for chronic hypoxemia.
5.Subjects with known α-1 antitrypsin deficiency as the underlying cause of COPD
6.Subjects with primary diagnosis of emphysema not related to COPD.
7.Subjects with clinically significant respiratory disorders other than COPD.
8.Subjects with lung volume reduction surgery.
9.Subjects having lung cancer or a history of lung cancer or lung cancer with full recovery less than 1 year after completing cancer therapy.
10.Subjects with active cancer or a history of cancer (other than the lung) with full recovery less than 1 year after completing cancer therapy or any untreated localized carcinoma.
11.Subjects with a history of allergy or hypersensitivity to anticholinergics, β2-agonists, corticosteroids, PDE-4 inhibitors or any of the excipients contained in any of the formulations used in the trial or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the investigator’s opinion would contra-indicate study participation.
12.Subjects under Roflumilast treatment within 6 months before study entry
13.Subjects with a diagnosis of depression, generalised anxiety disorder, suicidal ideation or behaviour that might, according to the investigator judgement, place the subject at undue risk.
14.Subjects who have clinically significant cardiovascular condition.
15.An abnormal and clinically significant 12-lead ECG finding in relation to the subject’s medical history that results in active medical problem which may impact the safety of the subject according to investigator’s judgement.
16.Subjects with a significant neurological disease including transient ischemic attack (TIA), stroke, seizure disorder or behavioural disturbances that in investigator’s opinion, would place the subject at risk by participating to the study.
For complete list of exclusion criteria, please refer to the protocol.

E.5 End points

E.5.1

Primary end point(s)

Annual rate of moderate and severe exacerbations over 52 weeks

E.5.1.1

Timepoint(s) of evaluation of this end point

Over 52 weeks

E.5.2

Secondary end point(s)

•Change from baseline in SGRQ Total score at week 52
•Time to first moderate/severe exacerbation
•Annual rate of severe exacerbations
•Time to first severe exacerbation
•The number of on-treatment severe exacerbations
•Change from baseline in morning pre-dose of FEV1 at week 52
•Change from baseline in SGRQ Domain scores at week 52
•SGRQ response (i.e., change from baseline in SGRQ score ≥ -4) at week 52
•Change from baseline to last inter-visit period (week 40-52) in the average E-RS total and sub-scale scores
•E-RS response (i.e., change from baseline in E-RS total score ≤ -2) at week 52
•Change from baseline to last inter-visit period (week 40-52) in the percentage of days without intake of rescue medication and in the average daily use of rescue medication (number of puffs)
•Time to study medication discontinuation due to any reason
•Time to first moderate or severe exacerbation or study medication discontinuation (due to any adverse events, lack of efficacy or death (composite endpoint) and time to its individual components (i.e. time to study medication discontinuation).

E.5.2.1

Timepoint(s) of evaluation of this end point

Over 52 weeks

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

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

174

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

Argentina

Chile

New Zealand

Ukraine

China

Israel

Mexico

Russian Federation

South Africa

Turkey

United Kingdom

Austria

Bulgaria

Czechia

France

Germany

Greece

Hungary

Italy

Netherlands

Poland

Romania

Slovakia

Spain

E.8.7

Trial has a data monitoring committee

Yes

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:

1985

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1000

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

183

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1618

F.4.2.2

In the whole clinical trial

2985

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)

NONE

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

2021-05-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-07

P. End of Trial
P.	End of Trial Status	Ongoing

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